Vaccines Have Serious Side Effects

The Revised Authoritative Guide To Vaccine Legal Exemptions

Comprehensive, authoritative information about vaccine exemptions you can trust, from Alan Phillips, J.D., a leading vaccine rights attorney with years of experience helping clients throughout the U.S. legally avoid vaccines in a wide variety of vaccine-refusal settings. Critical details for parents, students, immigrants, healthcare employees, military personnel and contractors, agencies, attorneys and clientsvirtually anyone concerned with legally avoiding vaccines in the United States. This Guide provides and explains: Important background information about the legal system; How state and federal statutes, regulations, constitutions and legal precedent interact to define the boundaries of your legal exemption rights; How to deal with local authorities and to avoid mistakes that cost others their exemption; Where legal technicalities and practical reality differand what to do about it; Read more here...

The Revised Authoritative Guide To Vaccine Legal Exemptions Overview


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Cholera Toxin Mechanism of Action and Potential Use in Vaccine Development

Cholera results from an intestinal infection with the pathogenic bacterium Vibrio cholerae that causes a debilitating, and even deadly, diarrhea. Successful treatment of cholera requires effective rehydration with solutions of glucose and salts (Kaper et a ., 1995). Administration of antibiotics decreases the duration of disease (Kaper et al., 1995) vaccines are only partially effective. Koch, who first described Vibrio cholerae as the causative agent of cholera, suggested that it was a toxin-mediated disease (Koch, 1884). Over a half-century later, the existence of cholera toxin (CT) was demonstrated in cell-free culture filtrates (De, 1959 Dutta et al., 1959) a decade later, purification of the protein toxin was achieved (Finkelstein and LoSpalluto, 1969). Since then, it has been found that CT is just one member of a family of erated for use as targeting molecules to direct covalently attached ligands to specific cells, or as adjuvants for use in vaccine development (Holmgren etal.,...

Practical Aspects of Cholera Toxin Use 131 Vaccine and Vaccine Development

Cholera vaccine would be an important contribution to the control of this potentially lethal diarrheal disease. Experiments in animals and humans have shown that both CT and the nontoxic CTB can induce immunogenicity strong intestinal IgA immune responses, when administered orally (Svennerholm, etal., 1978, 1984 Elson and Ealding, 1984 Quiding et al., 1991). The marked immunogenicity of CT and CTB may be due in part to their ability to bind to Gmi ganglioside on the surface of intestinal mucosal cells (Holmgren et al., 1994). It was recently suggested that the mucosal effects of CT in vivo could result from inhibition of certain mucosal T cell functions and alteration of the regulatory T cell environment in gut-associated lymphoid tissue (Elson etal., 1995). Two different types of oral vaccines are being developed (Mekalanos and Sadoff, 1994). One is a mixture of CTB and killed whole V. cholerae cells containing CT (Clemens et al., 1986). A large-scale field trial in Bangladesh proved...

Vaccination Strategies for Enhanced Immunity

Vaccination can be considered as a therapeutic modality that actively engages the immune system of the patient. It encompasses numerous principles derived from drug targeting research. Modification of the responses of the immune system may be an effective approach to improve the disease status of patients with a variety of diseases. Either prevention of au- toimmune diseases or allergic responses, or enhancement of immune responses against infectious agents and tumour growth can be induced by these strategies 95,96 . Vaccination strategies can be divided into gene-, peptide-, protein- and cell-based strategies. Antigen presenting cells (APC), particularly dendritic cells (DC), play a central role in the induction of the desired immune response 97 . For successful (antitumour) vaccination therapy, either an in vitro or an in vivo approach can be followed. In the in vitro approach, DCs from an animal or a patient are isolated and manipulated by transfection with DNA or RNA encoding...

Vaccines in Development

Quite a number of biotechnology-generated vaccines are in development (Table 4.10). Some of them are in the category of therapeutic vaccines. These vaccines are designed to bind to cellular receptors, endogenous molecules, and so on, producing specific pharmacological effects. For example, if a cell has a particular receptor that binds a ligand to activate the cell, binding an antibody raised by a specific vaccine to the receptor will prevent activation. If a tumor has a requirement for such a receptor-ligand binding, using a vaccine to develop antibody to the receptor or the ligand should prevent or slow cellular proliferation.

Immunobiologicals Vaccines and Toxoids610

A vaccine may be defined as a solution or suspension of killed or live attenuated virus, killed rickettsia, killed or live attenuated bacteria, or antigens derived from these sources, which are used to confer active, artificially acquired immunity against that organism or related organisms. When administered, the vaccine represents the initial exposure, resulting in the acquisition of immunity. A subsequent exposure or challenge (a disease) results in the anamnestic, or memory, response.

Haemophilus Influenza Type B Conjugate Vaccine

Hib-CV is a sterile, lyophilized capsular polysaccharide from Hib vaccine, conjugated to various protein fragments. The antigen type is polysaccharide (phosphoribosyl ribitol phosphate) conjugated to protein. The conjugation produces a stronger, longer-lasting response through the adjuvant effect. Hib-CV is safe and almost completely effective and is a mandatory part of the childhood immunization schedule. The various forms of Hib-CV on the market are not generi-cally equivalent. Indications are the following

O New Vaccine Technologies Adjuvant Technology

In spite of the long history of vaccines, only a few adjuvants and vaccine delivery systems have been licensed for human use. There are several reasons for this. Vaccines based on live-attenuated organisms are invasive and are efficiently delivered to APCs. Pattern-recognized components of the cellular pathogens are recognized by the innate immune system and trigger an innate response. With the trend of using subunit vaccines and isolated antigens, immune potentiators and delivery systems have become major issues in vaccine technology. Figure 5.12 Recommended immunization schedule for persons aged 7 through 18 years United States, 2009. (Available at child-schedule.htm printable. Accessed January 23, 2009.) Figure 5.12 Recommended immunization schedule for persons aged 7 through 18 years United States, 2009. (Available at child-schedule.htm printable. Accessed January 23, 2009.) The table below provides catch-up schedules and minimum intervals between doses tor children whose...

DNA vaccination for central nervous system autoimmune diseases

Conceptually, gene therapy has been used as an efficient methodology to circumvent genetic deficiency by transfection of cDNA encoding the appropriate functional gene product. It is therefore conceivable that the best candidates for this form of therapy would be genetic diseases associated with a single gene mutation, such as X-linked agammaglobulinemia (XLA) or cystic fibrosis (CF). Paradoxically, it appears that gene therapy needs to confront similar levels of technological challenges when encountering genetic disorders, such as XLA or CF, to those a involved in a successful intervention in multifactorial diseases. Yet, while genetic disorders that involve a mutation in a single gene are rare, multifactorial diseases comprise a major cause of illness and death in the developed countries. This has motivated scientists to explore gene therapy strategies in multifactorial disorders. This chapter discusses the use of a modification of gene therapy named DNA vaccination to provide novel...

Aluminium In Adsorbed Vaccines

Homogenise the preparation to be examined and transfer a suitable quantity, presumed to contain 5 mg to 6 mg of aluminium, to a 50 ml combustion flask. Add 1 ml of sulphuric acid R, 0.1 ml of nitric acid R and some glass beads. Heat the solution until thick, white fumes are evolved. If there is charring at this stage add a few more drops of nitric acid R and continue boiling until the colour disappears. Allow to cool for a few minutes, carefully add 10 ml of water R and boil until a clear solution is obtained. Allow to cool, add 0.05 ml of methyl orange solution R and neutralise with strong sodium hydroxide solution R (6.5 ml to 7 ml). If a precipitate forms dissolve it by adding, dropwise, sufficient dilute sulphuric acid R. Transfer the solution to a 250 ml conical flask, rinsing the combustion flask with 25 ml of water R. Add 25.0 ml of 0.02 M sodium edetate, 10 ml of acetate buffer solution pH 4.4 R and a few glass beads and boil gently for 3 min. Add 0.1 ml of pyridylazonaphthol...

Vaccinationa Way To Exploit Tcellmediated Autoimmunity For The Treatment Of Degenerative Disease

We were all taught that vaccination places the immune system on call for action, thus shortening the lag period between invasion of a particular microorganism and recruitment of the specific immune cells needed to fight it. Vaccination is not a preventative measure, in the sense that it does not stop the microorganism from invading, but it endows the individual with protection by making it possible for the immune system to cope promptly and appropriately with the consequences of the invasion. An analogous situation arises when the insult is caused by non-invaders. Just as conventional vaccinations cannot repulse microorganisms or alter the environment which they inhabit, there is no vaccination that will prevent a motor accident or a head trauma from happening yet here, too, vaccination can ensure speedy recruitment of the immune system by preparing it in advance to protect the individual against the pathological consequences of the trauma. Both types of vaccination are based on...

Test For Neurovirulence Of Live Virus Vaccines

For each test, use not fewer than ten monkeys that are seronegative for the virus to be tested. For each monkey, inject not more than 0.5 ml of the material to be examined into the thalamic region of each hemisphere, unless otherwise prescribed. The total amount of virus inoculated in each monkey must be not less than the amount contained in the recommended single human dose of the vaccine. As a check against the introduction of wild neurovirulent virus, keep a group of not fewer than four control monkeys as cage-mates or in the immediate vicinity of the inoculated monkeys. Observe the inoculated monkeys for 17 to 21 days for symptoms of paralysis and other evidence of neurological involvement observe the control monkeys for the same period plus 10 days. Animals that die within 48 h of injection are considered to have died from non-specific causes and may be replaced. The test is not valid if more than 20 per cent of the inoculated monkeys die from nonspecific causes serum samples...

Assay Of Diphtheria Vaccine Adsorbed

The potency of diphtheria vaccine (adsorbed) is determined by comparing the dose of the vaccine required to protect guinea-pigs from the effects of either an erythrogenic dose of diphtheria toxin administered intradermally or a lethal dose of diphtheria toxin administered subcutaneously with the dose of a reference preparation, calibrated in International Units, needed to give the same protection. Diphtheria vaccine (adsorbed) BRP is suitable for use as a reference preparation. The design of the assay described below follows a parallel-line model with 3 dilutions for the test and reference preparations. Once the analyst has sufficient experience with this method for a given vaccine, it is possible to apply a simplified model using a single dilution for both test and reference preparations. Such a model enables the analyst to determine whether the potency of the test preparation is significantly higher than the minimum required but does not give information on linearity, parallelism...

Assay Of Pertussis Vaccine

The potency of pertussis vaccine is determined by comparing the dose necessary to protect mice against the effects of a lethal dose of Bordetella pertussis, administered intracerebrally, with the quantity of a reference preparation, calibrated in International Units, needed to give the same protection. The International Unit is the activity contained in a stated amount of the International Standard which consists of a quantity of dried pertussis vaccine. The equivalence in International Units of the International Standard is stated by the World Health Organisation. Selection of the challenge strain and preparation of the challenge suspension. Select a suitable strain of B. pertussis capable of causing the death of mice within 14 days of intracerebral injection. If more than 20 per cent of the mice die within 48 h of the injection the strain is not suitable. Make one subculture from the strain and suspend the harvested B. pertussis in a solution containing 10 g l of casein hydrolysate...

Assay Of Pertussis Vaccine Acellular

The capacity of the vaccine to induce the formation of specific antibodies is compared with the same capacity of a reference preparation examined in parallel antibodies are determined using suitable immunochemical methods (2.7.1) such as enzyme-linked immunosorbent assay (ELISA). The test in mice shown below uses a three-point model but, after validation, for routine testing a single-dilution method may be used. Reference vaccine. A batch of vaccine shown to be effective in clinical trials or a batch representative thereof is used as a reference vaccine. For the preparation of a representative batch, strict adherence to the production process used for the batch tested in clinical trials is necessary. The stability of the reference vaccine shall be documented. Requirement. The capacity of the vaccine to induce antibodies is not significantly (P 0.95) less than that of the reference vaccine. Selection and distribution of test animals. Use in the test healthy mice (for example, CD1...

From Protein Subunit Vaccines to Antibody Treatments of Bacterial Infections

New strategies are needed to master infectious diseases. Ihe so-called passive vaccination, i.e., prevention and treatment with specific antibodies, has a proven record and potential in the management of infections and entered the medical arena more than 100 years ago. Progress in the identification of specific antigens has become the hallmark in the development of novel subunit vaccines that often contain only a single immunogen, frequendy proteins, derived from the microbe in order to induce protective immunity. On the other hand, the monoclonal antibody technology has enabled biotechnology to produce antibody species in unlimited quantities and at reasonable costs that are more or less identical to their human counterparts and bind with high affinity to only one specific site of a given antigen. Although, this technology has provided a robust platform for launching novel and successful treatments against a variety of devastating diseases, it is up till now only exceptionally...

Development of antiPE A vaccine

Pseudomonas aeruginosa are gram-negative bacilli and are among the most problematic opportunistic pathogens 15 . They are widely distributed in nature, and seldom infect healthy people. Yet, these bacteria still manage to infect immunodeficient individuals, such as patients suffering from burns, cystic fibrosis, cancer or patients who take immunosuppressive medicines 16-19 . Moreover, treatment of these infections is greatly impaired by the acquired resistance of P. aeruginosa to antibiotics 20 . Therefore, immunization against the P. aeruginosa infection may offer a promising approach to circumvent this difficulty. In the past decade, the outer membrane components, detoxified secretory toxins, toxoids, and high-molecular-weight polysaccharides, have been used as antigens for vaccination 17,18,21-26 . However, among all the identified pathogenic factors, PE A is the most toxic component and is considered to be the most virulent factor 27 . Thus, development of a vaccine against PE may...

Developing a multivalent vaccine for the prevention of Pseudomonas infection

Bacterial infection involves the adhesion and multiplication of the microbe in the host's target organ. However, in the case of the P. aeruginosa infection, it becomes more complicated than the usual bacterial infection, because the P. aeruginosa infection involves more stages, including adherence, colonization, invasion, dissemination, and systemic effects of toxemia. In addition, each stage in different strain of P. aeruginosa infection results in variable effects. Thus, the development of vaccines against the P. aeruginosa infection has become very difficult. Several potential vaccines, such as PE toxoid, elastase and alkaine protease toxoids, detoxified lipopolysaccharide-protein conjugates, polysaccharide-protein conjugates, and outer membrane proteins, were developed to repel the P. aeruginosa infection 36-42 . However, it seems unlikely that antibodies of a single cell-surface determinant or secreted protein can protect a P. aeruginosa susceptible patient. Therefore, the idea...

Application of the receptorbinding domain of PE A as an antigen deliver system for the development of antiGnRH

The induction of an immune response against specific self-peptides is potentially beneficial for the treatment of certain diseases. For example, most breast cancer patients overexpress HER2 neu oncoprotein and the prognosis usually is not good. A humanized monoclonal antibody to HER2 neu, named Herceptin, is now in clinical use in combination with chemotherapy, which gives promising therapeutic effects 46,47 . If we can develop a vaccine targeted at HER2 neu instead of applying a passive Herceptin antibody for breast cancer treatment, we could offer a low-cost alternative for cancer therapy. However, no such vaccine has been commercially launched yet, to the market. We, therefore, took the challenge to develop a therapeutic vaccine targeted at diseases that overexpress hormones or cell surface autoantigens. The results of self-peptide-based immunization in animals, however, have not been satisfactory because of the low immunogencity of self-peptides, the low efficiency of chemical...

Sialic Acid In Polysaccharide Vaccines

Prepare 2 series of 3 test-tubes, place in the tubes of each series 0.5 ml, 1.0 ml and 1.5 ml respectively, of the reference solution corresponding to the type of vaccine to be examined and adjust the volume in each tube to 2.0 ml with water R. Prepare blank solutions using 2.0 ml of water R in each of 2 test-tubes.

Assessment of HIV Vaccine Development Past Present and Future

Progress in AIDS Vaccine Development 276 B. Live Attenuated Vaccine 278 C. Whole-Inactivated Vaccine 279 D. Subunit Vaccine 281 E. DNA Vaccine 284 F. Live Vector Vaccine 287 VI. Factors to Consider in Designing an Envelope-Based Vaccine 290

Test For Neurovirulence Of Poliomyelitis Vaccine Oral

Monkeys used in the neurovirulence test comply with the requirements given in the monograph on Poliomyelitis vaccine oral (0215) and weigh not less than 1.5 kg. The pathogenicity for Macaca or Cercopithecus monkeys is tested in comparison with that of a reference virus preparation for neurovirulence testing by inoculation into the lumbar region of the central nervous system after sedation with a suitable substance, for example, ketamine hydrochloride. A sample of serum taken before Number of monkeys. The vaccine and the appropriate homotypic reference virus are tested concurrently in the same group of monkeys. Equal numbers of animals are inoculated with the vaccine to be examined and the reference preparation. The animals are allocated randomly to treatment groups and cages and their identity is coded so that the treatment received by each animal is concealed from the observers and the evaluators of the sections. The number of monkeys inoculated is such that in the evaluation of both...

Methods Of Vaccine Production

Vaccine production methods have varied greatly over the years and are best discussed according to a parallel chronological and sophistication approach. In this method, the normal pathogen is treated with a strong, denaturing disinfectant like formaldehyde or phenol. The process denatures the proteins and carbohydrates that are essential for the organism to live and infect a host, but if treated properly, the surface antigens are left intact. The process must be done carefully to control the unwinding of proteins or carbohydrates by denaturation, because the preparation must be recognized as the original antigen. The main problems with killed pathogen vaccines are the following (a) if the vaccine is not inactivated totally, disease can result (b) if the preparation is overtreated, vaccine failure usually results because of denaturation (c) the production laboratory must grow the pathogen in large quantities to be commercially useful, putting laboratory technicians at risk and (d) the...

Vaccines and Drug Specific Antibodies

In the context of psychopharmacology, vaccines are drug-protein conjugates that stimulate a subject's immune system Vaccines and drug-specific antibodies are currently being developed for the treatment of drug abuse. Most phar-macotherapies for drug abuse target the neuropharmaco-logical processes that mediate a drug's dependence-related behavioral effects by binding to associated receptors in the CNS ( Nicotine dependence and its treatment, Opioid Dependence and its treatment). In contrast, vaccines target the drug itself rather than the brain. Vaccines elicit the production of drug-specific antibodies that bind drug in blood and reduce its distribution into the brain. By acting outside the brain, a primary advantage of vaccines is that they lack the CNS side effects associated with CNS receptor-based pharmacotherapies that can alter normal neural function. Immunologic interventions such as vaccination or passive immunization were first suggested as a pharma-cologic approach to...

Assay Of Tetanus Vaccine Adsorbed

The potency of tetanus vaccine is determined by administration of the vaccine to animals (guinea-pigs or mice) followed either by challenge with tetanus toxin (method A or B) or by determination of the titre of antibodies against tetanus toxoid in the serum of the guinea-pigs (method C). In both cases the potency of the vaccine is calculated by comparison with a reference vaccine, calibrated in International Units. For methods A and B, in countries where the paralysis method is not obligatory the LD50 method may be used. For the LD50 method, the number of animals and the procedure are identical with those described for the paralysis method but the end-point is the death of the animal rather than paralysis. Tetanus vaccine (adsorbed) BRP is calibrated in International Units with reference to the International Standard. The method chosen for assay of tetanus vaccine (adsorbed) depends on the intended purpose. Method A or B is used 1. during development of a vaccine, to assay batches...


Vaccines and immunizing biologicals are covered thoroughly in Chapter 5 of this text, so no lengthy discussion is given here. Vaccine production is a natural application of rDNA technology, aimed at achieving highly pure and efficacious products. Currently, there are four rDNA vaccines approved for human use. A number of others are in clinical trials for some rather exotic uses. It would appear that biotechnological approaches to vaccines will bring about some very useful drugs. Recombivax and Engerix-B are interchangeable for immunization against hepatitis B virus (HBV, serum hepatitis). Both contain a 226-amino acid polypeptide composing 22-nm diameter particles that possess the antigenic epi-topes of the HBV surface coat (S) protein. The products from two manufacturers are expressed from recombinant S. cerevisiae. It is recommended that patients receive 3 doses, with the second dose 1 month after the first and the third dose 6 months after the first. The route and site of injection...

Rotavirus Vaccine

There is a rotavirus vaccine included in the Recommended Childhood Immunization Schedule. This vaccine is used to provide immunity against rotavirus, the most common cause of severe diarrhea in children in the United States. All children have at least one rotavirus infection in the first 5 years of life, and there are about 20 deaths per year in this country. Children between the ages of 3 and 24 months of age have the highest rates of severe disease and hospitalization. The rotavirus vaccine is an oral vaccine, given as a series of three doses. It is recommended that the vaccine be administered at 2, 4, and 6 months of age. The most common side effect seems to be fever.

Pertussis Vaccine

Pertussis vaccine has been highly controversial in recent years. The original vaccine consisted of killed pertussis bacilli (B. pertussis) and was considered somewhat dirty. Side effects such as fever and convulsions were common, and health authorities in the United States, Japan, and the United Kingdom decided that the risk of the vaccine outweighed the risk of contracting the disease. In all three of these countries, pertussis vaccine was removed from the routine immunization schedules. Almost immediately, pertussis, which had been held in check, began to occur in epidemics. In 1992, a new vaccine was developed that consists of bacterial fractions, combined with tetanus and diphtheria toxoids. This vaccine, called Acell-Immune, or diphtheria-tetanus-acellular pertussis (DTaP), is safe and highly effective and has been added to the routine immunization schedule. The vaccine is adsorbed and is used for routine immunization as the polyvalent preparation diphtheria-tetanus-pertussis...

Cholera Vaccine

Cholera is a disease caused by Vibrio cholerae that presents as severe, watery diarrhea caused by an enterotoxin secreted by the 01-serotype of V. cholerae. The disease occurs in pandemics in India, Bangladesh, Peru, and Latin America. The organisms never invade the enteric epithelium instead, they remain in the lumen and secrete their enterotoxin. There are about 17 known virulence-associated genes necessary for colonization and toxin secretion. Secretory diarrhea is caused by release of an enterotoxin called cholera toxin, which is nearly identical with E. coli enterotoxin. It is composed of five binding peptides B and a catalytic peptide A. The pep-tides B bind to ganglioside GM1 on the surface of the epithelial cells, setting in motion a series of events that causes diarrhea. The vaccine consists of whole cells of V. cholerae 01 that have been inactivated. The antigen form of the vaccine is whole bacterium, and the antigen type is protein toxin and lipopolysaccharide. Indications...

Pneumococcal Vaccine

Pneumococcus is also known as S. pneumoniae or diplococ-cus. The microorganism protects itself from the immune system by producing a capsular polysaccharide that is highly antigenic. This polysaccharide is used to prepare the vaccine. The antigen form of pneumococcal vaccine is capsular polysaccharide fragments, and the antigen type is a polysaccharide mixture. The antigen is 23-valent. The following are indications in the vaccine (the vaccine protects against pneumococcal pneumonia, pneumococcal bacteremia, and other pneumo-coccal infections)


Boosting declining immunity in the elderly could in theory prevent HZ and subsequent PHN. In the first program of its kind, nearly 39,000 immunocom-petent subjects over 60 years of age with a history of childhood varicella were randomized to receive live attenuated Oka VZV virus or placebo 3 . The incidence of HZ in the vaccinated group was 51.6 lower than in the placebo group during the mean follow-up of 3 years. There were fewer cases of PHN in the vaccine group than placebo group (0.46 case versus 1.38 cases, respectively, P < 0.001). PHN was defined as pain and discomfort > 3 10. Adverse effects were more common in the vaccine group, and were mostly experienced at the injection site. No increase was seen in serious side effects. The cost-effectiveness of this prevention has divided opinion 52-54 . Other vaccination projects are under way in Europe.

Cancer Vaccines

During the past two decades tremendous research efforts have been focused to the development of cancer vaccines, which are intended either to treat existing cancers (therapeutic vaccines) or to prevent the development of cancer (prophylactic vaccines). Some of these cancer vaccines have reached Phase III clinical trials,39 and the strategies developed to stimulate the immuno response to cancer include 1. Use of cancer cell antigens that are rarely present on normal cells. These antigens may be isolated from the same patient suffering the disease (personalized vaccines) or from another patient. The prime candidates as vaccination antigens have been antiapoptotic molecules such as IAP (inhibitor of apoptosis protein) and BCL-2 (see Section 6 of Chapter 9) because these proteins enhance the survival of cancer cells and facilitate their escape from cytotoxic therapies.40 3. Administration of antigen-presenting cells (APCs), such as the specialized white blood cells known as dendritic...

Viral Vaccines12

SMALLPOX VACCINE (DRYVAX) Smallpox vaccine is live vaccinia (cowpox) virus grown on the skin of a bovine calf. Smallpox is a highly lethal and disfiguring disease that was common throughout history. Smallpox vaccine was used routinely in the United States but today is no longer recommended. (There have been no reported cases of smallpox since the 1940s.) In 1982, smallpox was declared eradicated worldwide. With smallpox, the risks of the vaccine outweigh the benefits the vaccine penetrates the central nervous system and potentially fatal encephalitis occurs in 1 of l05 patients. After exposure to smallpox, the vaccine can be injected to lessen the severity of the disease. INFLUENZA VACCINE13-17 Influenza vaccine is a multivalent inactivated influenza virus or viral subunits (split vaccine). The virus is grown on chick embryo and inactivated by exposure to ultraviolet (UV) light or formaldehyde. The antigen type is protein. The vaccine in the United States contains thimerosal, a...

Tuberculosis Vaccine

Tuberculosis (TB) is a serious disease caused by Mycobacterium tuberculosis. The organism becomes established in the lungs and forms walled-off abscesses that shield the bacterium from the immune system. The disease is diagnosed by a chest radiograph. Until the 1940s, persons with TB were sent to sanatoria, special hospitals to isolate TB patients. The vaccine is referred to as the bacillus Calmette-Guerin (BCG) vaccine and is a live attenuated strain of Mycobacterium bovis. The antigenic form is the whole bacterium, and the antigen type is protein. The vaccine is of questionable efficacy and has been judged only 50 to 77 effective. The duration of protection is highly questionable. The incidence of TB in the United States is so low that the vaccine is not indicated in most cases. Indications are An adverse effect of the BCG vaccine includes a positive TB skin test. A red blister forms within 7 to 10 days, then ulcerates and scars within 6 months. BCG is a live vaccine,

Biopharmaceuticals an overview

Biopharmaceuticals approved to date include blood factors, anticoagulants and thrombolytic agents, therapeutic enzymes, hormones and haemopoietic growth factors. Also approved are a number of interferons and an interleukin. Recombinant vaccines and several monoclonal antibody based products are also now on the market.

Historical Perspective

Humans have always attempted to improve their health by ingesting or administering drugs. Examples appear throughout written history, from every continent and culture. Noah produced alcohol 1 and Christ was offered a sedative to ease the pain of crucifixion 2 , The use of opium was described by Theophrastus in the third century b.c., the stimulating power of methyl-xanthines was exploited by ancient Arabian shepherds and priors, and the paralyzing properties of curare were recognized by native South Americans centuries before the arrival of Sir Walter Raleigh 3 , The chemotherapy of cancer, which many consider a modern development, has existed in some form for over 500 years 4 . Vaccination, the intentional exposure to pathogens, was used in China and India to prevent smallpox and other infections 5 centuries before the birth of either Jenner 6 or Pasteur 7 . Even during the 20th century, drug discovery frequently resulted from empiricism and happenstance. The anticancer effects of...

Present status of the basic features of artificial cells of macro micron nano and molecular dimensions

The general principles of artificial cells can form the basis of a large number of artificial systems (Fig. 2.1). In addition to being of cellular dimensions in the micron range, they can also be in the macro range, nano range or molecular range. Furthermore, the membrane material includes polymer, biodegradable polymer, lipid, crosslinked protein, lipid-polymer complex, lipid-protein complex and membrane with transport carriers. Artificial cells can contain an unlimited variety of material individually or in combinations (Fig. 2.1). These include cells, stem cells, enzymes, multienzyme systems, hemoglobin, magnetic materials, microorganisms, vaccines, genes for gene therapy, genetically engineered cells, adsorbents, drugs, hormones, peptides, proteins and others.

Drug Administration and Drug Effectiveness

Perhaps for this reason, the modern practice of healing usually involves medicine, an agent or elixir given as treatment.1 The new millennium finds us rich in the knowledge of agents advanced in the art of harvesting or synthesizing remedies steadfast in the belief that cancer, heart disease, and neurodegeneration will eventually yield to these potions. Our skill in making medicine is far-reaching. Today, it would be difficult to find the person who has not personally experienced the healing force of antibiotics, vaccines, or modern chemotherapy. Unfortunately, it would be equally difficult to find the person who has not endured the premature death of a friend or relative due to unbeatable infection or cancer. So we continue to search for better therapeutics.

From Fingerprinting To Structural Investigation

When using Curie-point filament pyrolysis, additivity of spectra is readily observed for such classes of compounds as polysaccharides (refs. 65, 66) and lignins (ref. 67) and, less well established, also for lipids and proteins (ref. 68). The additivity of component subspectra is an important requirement for (semi)quantita-tive applications of Py-MS, e.g. in monitoring ppm concentrations of the toxic, technical polymer DEAE-dextran in poliomyelitis virus vaccine preparations (ref. 63).

Box 21 Fda Plans To Shift Review And Approval Of Wellcharacterized And Recombinant Biotechnology Products From Its

Under the revised system, CBER will continue to review blood products and vaccines. These product areas are CBER's strengths and the basis for creation of the biologics division. CBER will also be responsible for evaluating gene therapy and tissue transplantation products as the development of these novel entities comes to fruition. Even with these regulatory changes, manufacturing and assay costs for biologic macromolecules remain much higher than for traditional drugs. Biologics not considered to be well-characterized, such as blood and tissue and their components and inactivated vaccine antigen preparations, continue to be developed, manufactured, and reviewed for approval under pre-1996 regulations.

Biodegradable polymeric artificial cells nanoparticles nanocapsules

Biodegradable membrane artificial cells have been prepared to contain enzymes, hormones, vaccines, and other biologicals (Chang, 1976a). The polylactide polymer can degrade in the body into lactic acid and finally into water and carbon dioxide. In the same study, variations in preparation can result in artificial cells that release insulin at different rates (Chang, 1976a). Biodegradable drug delivery systems are now used widely in different forms, ranging from microscopic to nanodimensions (LaVan et al., 2002). They are also known as nanoparticles, nanocapsules, polymersomes, nanotubules, etc.

Measuring Immune Responses

Non-invasive measures of immune function include documentation of infection rates, number of days of fever, days of use of antibiotics and consequent days of hospitalization. Invasive measures are defined as those which require either the non-oral administration of agents to the subject or the removal of blood or other internal body fluids. Invasive measures of immune function include delayed-type hypersensitivity (DTH) skin test responses discussed in detail below blood sample analyses for number and types of white blood cells, antibody titres to vaccines, serum concentrations of acute phase proteins and virus concentrations. Determination of white blood cell classes has improved considerably with the advent of the fluorescence-activated cell sorter which provides an accurate and rapid means for determining subsets of immune cells, their receptors and their state of activation. Functional assays of immune cells, such as NK cell function, macrophage and neutrophil phagocyte functions,...

The Health of Our Nation

As a nation we have made significant progress in controlling many diseases and reducing mortality rates through public health programs, research, education, health care, and advances in medical technology. Vaccination and food fortification programs have virtually eliminated some of the most devastating diseases, such as polio, typhoid, and rickets, common in previous generations. But chronic diseases associated with aging and longer life expectancies, especially among racial and ethnic groups, have brought new challenges. Americans reporting fair or poor health due to chronic health conditions increases significantly with age.12

Clinical studies in the elderly multivitamins

In another placebo-controlled intervention trial, elderly subjects with marginal intakes of several vitamins were given a multivitamin daily for 1 year which contained approximately eight times the standard level of intake of p-carotene (16 mg). The supplemented group had significantly fewer infections than the placebo group. Responses to influenza vaccine, as measured by increased antibody titres, were also improved in the supplemented group (Chandra, 1992). associated deaths reported in 1991 in the USA, more than 90 were in persons aged 65 and older. For bacterial pneumonia, there is a vaccine, which, however, is only 56 effective in preventing pneumococcal pneumonia, the most common cause of bacterial pneumonia. Currently, only 28 of the elderly receive pneumococcal vaccination 52 receive influenza vaccination. Thus, it is especially important to improve immune responses in this at-risk population because another major consequence of reduced immune responses in the elderly is...

Vitamin E studies in the elderly

Two placebo-controlled, double-blind studies conducted in the elderly have found that vitamin E supplementation alone can significantly enhance DTH responses, antibody titres to certain vaccines, and proliferative responses as well as IL-2 activities. In a carefully controlled study conducted in a metabolic ward where the daily diet contained approximately RDA levels of all nutrients, vitamin E supplementation (800 IU day-1) for 1 month resulted in significantly increased DTH responses of healthy elderly subjects (Meydani et al., 1990). Lymphocyte vitamin E levels increased over threefold with supplementation and were correlated with enhanced immune responses such as enhanced IL-2 production. The vitamin E-supplemented Meydani et al. (1997) extended their earlier findings and examined the effects of 6 months of supplementation with 60, 200, or 800 IU day-1 of vitamin E in a placebo-controlled, double-blind study in healthy, free-living elderly subjects. In addition to DTH responses,...

Developing a Novel Biopharmaceutical

Since the introduction of biotechnology to health sciences, many new, previously unavailable proteins and peptides for therapeutic purposes have been introduced. The agents include (1) factors that influence hematopoietic cells and blood coagulation, (2) interferons and cytokines for anti-infective and cancer therapy, (3) hormones and derivatives, (4) enzymes and derivatives, and (5) recombinant proteins for vaccines. Examples of hematopoietic growth and coagulation factors are ery-thropoietin, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), clotting factors Vila, VIII, and IX, GPIIb IIIa inhibitors that affect platelet function, direct thrombin inhibitors, and antihemophilic factor. Several interferons are now available for the treatment of viral infections and some cancers. Numerous hormones, including glucagon, somatotropin, calcitonin, somatostatin, thyroid-stimulating hormone, thyrotropin-releasing hormone (Protirelin),...

Adverse reactions to drugs

Suspected adverse drug reactions to any therapeutic agent should be reported, including drugs (self-medication as well as those prescribed), blood products, vaccines, radiographic contrast media, complementary and herbal products. Newer drugs and vaccines Only limited information is available from clinical trials on the safety of new medicines. Further understanding about the safety of medicines depends on the availability of information from routine clinical practice. Established drugs and vaccines Healthcare professionals and coroners are asked to report all serious suspected reactions to established drugs (including over-the-counter, herbal, and unlicensed medicines and medicines used off-label) and vaccines. Serious reactions include those that are fatal, life-threatening, disabling, incapacitating, or which result in or prolong hospitalisation they should be reported even if the effect is well recognised. Examples include anaphylaxis, blood disorders, endocrine disturbances,...

General Socioeconomic Factors

The successful introduction of new DDW drugs and vaccines in developing countries should take into account that new interventions have to be (a) available to the global market place, development agencies, health services, and patients in developing countries (b) affordable for the end-user and for those institutions or governments who finance procurement and distribution (c) acceptable to government regulatory and policy makers, development agencies, health services, and end-users, which presupposes technological, economic, and social acceptability (d) socially and culturally acceptable to the population to be treated and (e) readily adoptable by government policy makers, development agencies, health services, and end-users 52 .

New Commitments to Combat Neglected Diseases

Since the beginning of the twenty-first century, there has been an explosion in the number of PPPs, also called product development partnerships (PDPs), created to address specific health problems of DDW. The Initiative on Public-Private Partnerships for Health listed 92 such partnerships in its partnerships database These PPPs are dedicated to finding and or implementing solutions for DDW, including developing new drugs and vaccines, diagnostics, use of impregnated bed nets, and access to affordable medications. The main PPPs dedicated to the development of new drugs for DDW are listed in Table 4. The availability of funding streams that were not available in the past, including the new wave of scientific and corporate responsibility by pharmaceutical companies, academic institutions, governments, and philanthropies, has stimulated activity in neglected diseases R& D. Recent funding programs include The US Leadership against HIV AIDS, Tuberculosis, and Malaria Act of 2003 http and...

Current Model for the RD of New Drugs for Ddw Ppps

Governments of low income countries in endemic areas have neither resources nor infrastructure to address the discovery and development of new drugs and vaccines. A new model to discover and develop those drugs was needed. That model, based in a network of partnerships, started to take shape in the last decade of the twentieth century, and currently is in the implementation and optimization phase. From the scientific point of view, the leading partners are both academia and the pharmaceutical industry. Funding comes primarily from governments and a few philanthropic foundations, particularly the Bill and Melinda Gates Foundation (BMGF), who contributes to helping establish strategic directions and priorities and providing resources in an unprecedented way. The PPPs have fundamentally modified the way in which new drugs for neglected diseases are developed, and are working to establish a robust pipeline for many of the DDW diseases, particularly malaria, TB, diarrhea, and the...

Computer Assisted Quantitative Analysis Of Mixtures

In case a factor describes one chemical component in a complex mixture, the factor score can be used as a quantitative measure of the compound. This is demonstrated in the application of Py-MS to the detection of ppm levels of impurities of the toxic, technical polymer diethylaminoethyl(DEAE)-dextran in batches of poliomyelitis virus vaccine as shown in Figure 34. By introducing standard virus preparations, spiked with 20, 40, or 80 ppm of DEAE-dextran in the sample series, the first factor described this polymer. Concentrations in the samples to be checked can be determined down to 20 ppm (ref. 63).

Genomeproteome Content Currently Used For Biomarker Research

Infectious disease biomarker discovery faces challenges as well. Purified proteins of many infectious agents are scarce. Purified protein microarrays of pathogens usually include only a handful of proteins. The lack of content has been the major reason for the slow rate of emergence of new serodiagnostic markers. For example, only 149 out of the 4198 ORFs (3.5 ) constituting the Yersinia pestis proteome were used to profile the antibody response to live vaccine 8 . In addition, 156 out of approximately 1000 (15.6 ) Chlamydia trachomatis proteins were used to profile the human humoral immune response to urogenital tract infections in human subjects 9 . The ability to express and purify recombinant proteins in the lab limits the amount of unique content available for serological screening. This low percentage of proteome coverage is common, and most laboratories in this field are studying a few antigens at a time from thousands of possible candidates.

Using Whole Proteome Microarrays To Screen For Disease State Discriminatory Antigens

The ability to find biomarkers relies on the ability to profile the immune response to entire proteomes. Antigens that are highly reactive to infection, or auto-antibodies, can be used in diagnostics and therapeutics. They are also potential candidates for the development of vaccines. Using the model organism vaccinia virus Western Reserve strain, researchers were able to use in vivo recombination cloning to clone the 185Vv proteins, or greater than 90 of the proteome, from genomic DNA into an expressible vector. This proteome vector library was subsequently expressed and arrayed onto nitrocellulose-coated slides. Each slide contains 16 nitrocellulose pads with a Vv proteome array per pad. Each slide is capable of producing serological data for 16 serum samples interrogating approximately 200 spots (185Vv proteins plus controls), yielding 3200 data points per slide, the equivalent of thirty-three 96-well ELISA plates. Davies et al. 22 showed that there are specific vaccination - state...

Issues and Opportunities

Computational tools and informatics tools facilitate data analysis and hypothesis generation. System biology approaches can be used to obtain a more integrated view of pathogen biology and pathology. Modern drug discovery technologies which are of common use in the R& D of other human diseases, including HTS, robotized and miniaturized screening assays, molecular modeling, genetic and proteomic studies, and molecular epidemiology, are now beginning to have wide-scale application to DDW. New funding and an increasing wave of social responsibility are attracting more scientists, project managers, and a network of organizations focused on new drugs and vaccines R& D to the area. All of these factors create a tremendous opportunity for the discovery of new DDW drugs.

Global Molecular Epidemiology of HIV Understanding the Genesis of AIDS Pandemic

Circulating recombinant forms (CRFs). Molecular epidemiological method has been useful tool to analyze the origin of HIVs and to track a course of global HIV dissemination. It could also provide the information critical to prevention and future vaccine strategies. In this chapter, we describe the classification and distribution of HIV genotypes and the biological and public health implications of genetic variability of this deadly pathogen.

Conclusions and Perspectives for the Future

The use of the C. difficile toxins as tools should obviously not be restricted to basic cell biological applications. The possibility of using the toxins, or fragments of them, for vaccination purposes should be investigated. Moreover, it is tempting to suggest that potent cytotoxins like these might be useful in targeted tumor therapy. The recent study of Riegler and coworkers (1995) indicated that 3 nM ToxA had no effect on human colonic mucosal sheets, at least during a 5h exposure. On the other hand as little as 0.01 -0.001 nM ToxA was shown to kill a variety of human colonic and pancreatic tumor cell lines, while 12-500 times more toxin was needed to kill cell lines derived from normal tissues (Kushnaryov etal., 1992). Is there a possibility of using ToxA locally as an antitumor agent directed against colon cancer

Future Outlook Conclusion

After decades of neglect, the situation regarding DDW is improving significantly. A new awareness of the dimension of the problem, and new funding streams, has prompted the creation of PPPs which have stimulated all aspects of neglected diseases. More pharmaceutical companies, research institutions, and academic groups are becoming engaged in and committed to third-world diseases, forming consortia of academic and industrial groups that are working together to discover new drugs and vaccines for DDW. In the long term, prophylaxis by vaccination may be the definitive solution. However, the flow of vaccines will be slow and will take, at least, the next 10-20 years. For some diseases, this time will be even longer. Thus, although vaccines will increase their importance in the control of DDW in the next decade, drugs will have a primary role for at least the next two decades.

Brain To Body Central Nervous System Effects On The Immune System

Although the relationship between stress and immunity is quite complex, more acute and or mild stressors, in general, tend to be associated with activation of immune responses, whereas more chronic and intense stressors tend to be associated with activated innate immune system elements and impaired acquired immune system responses. The health relevance of these stress-related immune changes has been demonstrated in studies that have shown an association between chronic stress and increased susceptibility to the common cold, reduced antibody responses to vaccination, and delayed wound healing (Cohen et al. 1991 Glaser et al. 1992 Kiecolt-Glaser et al. 1995). In addition, stress, as well as depression, has been linked to increased morbidity and mortality in infectious diseases (e.g., HIV infection), neoplastic diseases (including breast cancer and malignant melanoma), diabetes, and cardiovascular disease (Evans et al. 2005 Fenton and Stover 2006 Leserman et al. 1999 Raison and...

Postherpetic neuralgia

Postherpetic neuralgia (PHN) follows herpes zoster infections, mainly in the elderly. It occurs in the affected area in about 50 percent of patients over 50 years old following healing of the skin lesions, and persists for more than 12 weeks. It presents as a continuous burning or intense paroxysmal pain, and may be associated with tactile allodynia. It can be severe, debilitating, and reduce quality of life. The time-course is variable. It may abate within months, but may also continue for years. Certain human leukocyte antigen (HLA) class I antigens, such as HLA-A33 and -B44, have been shown to be associated with the development of PHN in Japanese patients.39 The results of randomized, controlled trials and meta-analyses suggest that treatment with acyclovir, famciclovir, and valaciclovir reduce the risk of developing PHN.40,41,42 It is now accepted that corticosteroids do not prevent the development of PHN.43 Topically applied capsaicin and lidocaine have both been shown to be...

Culture Method Choice Of Culture Media

Acholeplasma laidlawii (vaccines for human and veterinary use where an antibiotic has been used during production) Mycoplasma gallisepticum (where avian material has been used during production or where the vaccine is intended for use in poultry) Mycoplasma hyorhinis (non-avian veterinary vaccines) Mycoplasma orale (vaccines for human and veterinary use) Mycoplasma pneumoniae (vaccines for human use) or other suitable species of D-glucose fermenter Mycoplasma synoviae (where avian material has been used during production or where the vaccine is intended for use in poultry).

Therapeutic Applications of CpG Oligonucleotides

As a result of the activation of both innate and adaptive immunity, CpG ODNs can be applied in the therapy of cancer, infectious diseases, and asthma and or allergy, but also as highly effective adjuvants in vaccination.50 The therapeutic approaches in cancer and antiviral therapy involve both mono-therapy and combination therapies. TLR9 agonists are attractive drug candidates capable of triggering T helper cell 1 (Th1)-type immune responses (e.g. secretion of Th1-promoting chemokines and cytokines).14,51 B-class CpG ODNs have also been studied for their adjuvant effects when combined with commercial vaccines, such as the hepatitis B virus (HBV) vaccine Engerix-B.25 Vaccination using a combination of Engerix-B vaccine and CpG ODN resulted in a significant improvement as compared to the HBV vaccine alone, since the HBsAG-specific Ab responses appeared sooner and levels were significantly higher in volunteers receiving CpG ODN as adjuvant. Vaximmune is currently under investigation as a...

First grazing season calves

1988) assessed the efficacy of the programme in controlling both PGE and PB, with focus on control or eradication of D. viviparus or for farmers who cannot use an oral lungworm vaccine (see pages 240-241). The more recent studies focused more on the use of the programme in preventing PGE (Hollanders et al, 1992 Taylor et al, 1995a,b Vercruysse et al, 1995a). In the first studies (Taylor et al., 1985), questions about second season immunity and grazing season duration became a concern, particularly in view of the finding of Armour et al. (1988) of high burdens of inhibited

Therapeutic Opportunities In The Early Stages Of Ad Pathology

Another approach for therapeutic intervention that could prevent Ap aggregation and deposition is immunization with Ap peptides or vaccination with antibodies directed against the Ap peptide. The first report on immunization of PDAPP transgenic mice with the Ap peptide showed reduced amyloid plaque formation 84 . Subsequent reports not only confirmed the potential of immunization strategies to induce clearance of Ap, but also indicated the potential of reducing cognitive dysfunction (reviewed by 85 ). An immunization approach could work on different conformations of Ap and in different pathological stages. First, immunization increases the efflux of Ap out of the brain, into the periphery where it is degraded 86 . Peripheral administration of an antibody directed against Ap could results in a rapid decrease of oligomeric and low fibrillar Ap in the brain in an early stage of the disease. Second, antibodies directed against Ap can reduce the cytotoxic effect which Ap, especially the...

Epidemiology of Cattle Parasites and Cattle Management in North America

Generally, parasitic infections in North American cattle are subclinical apart from the exceptional situation of high stocking densities in the southeastern USA in late winter or early spring. However, productivity responses to ML treatment can be shown in rapidly growing animals on pasture or on drylots even when faecal egg counts are relatively low. Inconsistent productivity responses are seen after ML treatment of older cows on low stocking densities with adequate forage, but higher stocking densities and or poor forage result in productivity benefits for treatment (cow body conditioning scores, calf birth weights and calf weaning weights) even in adult cows (Reinemeyer, 1992). Some research has been conducted on the impact of deworming on immune responses in young calves (Klesius et al., 1984 Yang et al., 1993 Gasbarre, 1994,1997 Almeria et al., 1998). This research would support an enhanced immune response by reduction in Ostertagia burdens. This area of research may provide...

Lessons Learned From The Discovery And Development Of Histamine H2Receptor Antagonists

Finally, research in a particular disease area does not stand still even when a successful drug such as cimetidine is discovered. The proton pump inhibitors represent a significant further advance in antisecretory therapy, and if vaccination can eradicate H. pylori, then peptic ulcer may be a disease of the past.

Antiviral Activity of Botanical Polysaccharides

Current medical approaches available for controlling and preventing viral infections, such as influenza, include use of vaccines and antiviral agents 247 . On the other hand, nonspecific enhancement of host immune responses has also been proposed as an effective strategy to provide prophylactic protection against infectious diseases 275 . Indeed, botanical polysaccharides have attracted much attention because of their broad spectrum of therapeutic properties and their relatively low toxicity (reviewed in 3, 4 ). Therefore, efforts have focused on the discovery of novel polysaccharides from edible natural resources that either have direct antiviral activity or can act as therapeutic agents to nonspecifically enhance host defence against viral infections. were modified by sulfation. Likewise, oral treatment with exopolysaccharides from halophilous cyanobacterium Aphanothece halophytica Fremy significantly inhibited pneumonia in influenza virus A (H1N1)-infected mice 285 . Application of...

Prevention Of Hz And

At this time the use of an effective live attenuated, Oka strain, varicella vaccine given during childhood is standard in some geographic areas, notably the USA, and it seems likely that vaccinated populations will not develop varicella to a large extent (protection of the individual combined with a herd immunity effect) and are therefore not subject to HZ from wild-type (natural) VZV. Reactivation of Oka strain virus appears to be infrequent and mild. The same attenuated virus has been utilized in a higher dose form for vaccination of seropositive adults to prevent HZ and its complications. The greater strength is required because older adults have a reduced immune response compared with younger persons. The Shingles Prevention Study (SPS) investigated 38,546 subjects of > 60 years of age who were injected either with the active vaccine or placebo. They were followed for a median of 3.12 years and the incidence of HZ was reduced by 51.3 percent, PHN (defined as pain rating > 3 90...

Antibody Specifications For Sera Used In Extraneous Agents Testing

All batches of serum to be used in extraneous agents testing either to neutralise the vaccine virus (seed lot or batch of finished product) and all batches of avian serum used as a supplement for culture media used for tissue culture propagation, shall be shown to be free of antibodies against and free from inhibitory effects on the following micro-organisms by suitably sensitive tests Batches of sera prepared for neutralising the vaccine virus must not be prepared from any passage level derived from the virus isolate used to prepare the master seed lot or from an isolate cultured in the same cell line.

Tests For Turkey Rhinotracheitis Virus

Prepare 11 monolayers of primary or secondary chick embryo fibroblasts from the tissues of 9- to 11-day-old embryos, each monolayer having an area of about 25 cm2. Remove the culture medium when the cells reach confluence. Inoculate 0.1 ml of test vaccine onto each of 5 of the monolayers (test monolayers). Allow adsorption for 1 h, and add culture medium. Inoculate 4 of the monolayers with a suitable strain of turkey rhinotracheitis virus as positive controls (not more than 10 CCID50 in 0.1 ml). Maintain 2 non-inoculated monolayers as negative controls. monolayers or in any of the negative control monolayers, or if the results for both of the 2 negative control monolayers are inconclusive. If the results for both of the 2 test monolayers are inconclusive then further subcultures of reserved portions of the fibroblasts shall be made and tested until an unequivocal result is obtained. The batch of vaccine complies with the test if there is no evidence of the presence of turkey...

Test For Duck Enteritis Virus

This test is carried out for vaccines prepared on duck or Prepare 11 monolayers of primary or secondary Muscovy duck embryo liver cells, from the tissues of 21- or 22-day-old embryos, each monolayer having an area of about 25 cm2. Remove the culture medium when the cells reach confluence. Inoculate 0.1 ml of test vaccine onto each of 5 of the monolayers (test monolayers). Allow adsorption for 1 h and add culture medium. Inoculate 4 of the monolayers with a suitable strain of duck enteritis virus (not more than 10 CCID50 in 0.1 ml) to serve as positive controls. Maintain 2 non-inoculated monolayers as negative controls. Incubate the cultures for a total of at least 21 days, subculturing at 4- to 5-day intervals. Each passage is made as follows trypsinise the cells and prepare separate pools of the cells from the test monolayers, from the positive control monolayers and from the negative control monolayers. Mix a portion of each with a suspension of freshly prepared primary or secondary...

Test For Duck And Goose Parvoviruses

This test is carried out for vaccines prepared on duck or goose substrates. Prepare a suspension of sufficient primary or secondary Muscovy duck embryo fibroblasts from the tissues of 16- to 18-day-old embryos, to obtain not fewer than 11 monolayers, each having an area of about 25 cm2. Inoculate 0.5 ml of test vaccine into an aliquot of cells for 5 monolayers and seed into 5 replicate containers to form 5 test monolayers. Inoculate 0.4 ml of a suitable strain of duck parvovirus (not more than 10 CCID50 in 0.1 ml) into an aliquot of cells for 4 monolayers and seed into 4 replicate containers to form 4 positive control monolayers. Prepare 2 non-inoculated monolayers as negative controls. The batch of vaccine complies with the test if there is no evidence of the presence of duck (or goose) parvovirus or any other extraneous agent.

General Principles Ofantimicrobial Therapy

The emergence of antibiotic resistance in bacterial pathogens is a serious development that threatens the end of the antibiotic era. More than 70 of the bacteria associated with hospital-acquired infections in the U.S. are resistant to one or more of the drugs previously used to treat them. This rampant spread of antibiotic resistance mandates a more responsible approach to antibiotic use. The Centers for Disease Control and Prevention (CDC) has outlined a series of steps to diminish antibiotic resistance, including appropriate use of vaccination, judicious and proper use of indwelling catheters, early involvement of infectious disease experts, antibiotic selection based on local patterns of susceptibility, proper antiseptic technique to ensure infection rather than contamination, appropriate use of prophylactic antibiotics in surgical procedures, infection control procedures to isolate the pathogen, and strict compliance to hand hygiene.

Dilution Of The Test And Reference Preparations

Using a 9 g l solution of sodium chloride R, prepare dilutions of the vaccine to be examined and of the reference preparation, such that for each, the dilutions form a series differing by not more than 2.5-fold steps and in which the intermediate dilutions, when injected subcutaneously at a dose of 1.0 ml per guinea-pig, protect approximately 50 per cent of the animals from the paralytic effects of the subcutaneous injection of the quantity of tetanus toxin prescribed for this test.

Short Cut for the Future

Bacterial infectious diseases remain a major cause of deaths and disabilities in the world. Although conventional vaccinology approaches were successful in conferring protection against several diseases, they failed in providing efficient vaccines against many others. Together to the sequencing of the first genome, a new chapter in the vaccinology history started to be written. Reverse vaccinology changed the way to think about vaccine development, using the information provided by the microorganisms' genome against themselves. Since then, reverse vaccinology has evolved and helped researchers to overcome the limits of the conventional vaccinol-ogy approaches and led to the discovery and development of novel vaccines concerning emerging diseases, like Neisseria meningitidis B and Streptococcus agahctiae. A lot of work must be done, but deciphering the information provided by genome sequences and using it to better understand the host-pathogen interactions has proved to be the key for...

Control of ectoparasites

In the summer rainfall and tropical subtropical zone, B. microplus can be controlled by combining the tick vaccine (at present not being marketed) with early season (spring rise) broad spectrum ML parasiticide treatment and strategic plunge dipping (amidine or synthetic pyrethroids) in spring and early summer (O'Sullivan, 1998). This type of integrated programme reduces pastoral larval tick contamination levels throughout the season. Timing of treatment will be based on local property conditions and historical parasite patterns. Younger stock (< 18 months old) are most at risk at this time because they will be most

Test In Chicks Or Guineapigs

Prepare a suitable series of not fewer than 3 dilutions of the vaccine to be examined using a suitable buffered saline solution. Distribute either guinea-pigs weighing 250-350 g or 3-week-old chicks into groups of 10, and allocate a group to each dilution of the vaccine. Inject intramuscularly into each animal 0.5 ml of the dilution intended for its group. Bleed the animals after 5-6 days and separate the sera. Examine the sera for the presence of neutralising antibodies, at a dilution of 1 in 4, to each of the human polioviruses 1, 2 and 3. Mix 100 CCID50 of virus with the dilution of serum and incubate at 37 C for 4.5-6 h. Keep at 5 3 C for 12-18 h where necessary for consistency of results. Inoculate the mixtures into cell cultures for the detection of unneutralised virus and read the results up to 7 days after inoculation. For each group of animals, note the number of sera which have neutralising antibodies and calculate the dilution of the vaccine giving an antibody response in...


Recent reviews list more than 400 biotechnology-based pharmaceutical formulations either registered in clinical trials or undergoing review by the regulatory agencies for the treatment of nearly 150 diseases including cancer, infectious diseases, autoimmune diseases, and AIDS HTV (1,2). Biotechnology-based pharmaceuticals already on the markets include recombinant blood factors, recombinant hormones, cytokines, vaccines, monoclonal antibody-based products, and therapeutic enzymes.

Daniela Peruzzi Barbara Cipriani Agostino Cirillo Bruno Ercole Bruni Annalisa Meola Alfredo Nicosia Riccardo Cortese

Adenovirus (Ad) is an attractive vector for genetic vaccination due to its ability to infect several tissues. This property is impaired by pre-existing immunity to the human adenoviruses in most humans. Therefore finding uncommon alternative Ad serotypes becomes a priority. We have used a chimpanzee Adeno serotype 3 (E1,E3 deleted, ChAd3) engineered to express the human carcinoembryonic antigen (CEA) protein to vaccinate CEA. Tg mice in which human CEA shows a tissue distribution similar to that of humans. Animals were intramuscularly immunized with ChAd3-CEA and expression of human CEA was monitored in the serum. Development of a CEA-specific CD8+ T cell response was observed after a single injection and was comparable, in terms of efficacy and kinetics, to that of mice immunized with a similar vector based on human serotype 5 (Ad5-CEA) expressing CEA. Importantly, the capability of ChAd3-CEA to elicit an immune response against CEA was not abrogated in animals pre-exposed to human...

Gene therapy the real diseases

There is now good evidence that at least some tumours express tumour antigens that can be recognised under certain circumstances by the immune system (Boon et al., 1994). Therefore, it has been proposed that expression of various types of immunostimulatory molecules in tumour cells might enhance immune recognition, possibly by overcoming intrinsic defects in the pathways of antigen presentation by tumour cells (Pardoll, 1993). The hope is that tumour cells engineered to express such molecules, either ex vivo as vaccines or directly by in vivo gene delivery, will generate long-lasting immunity to unmodified tumour cells growing at distant sites in the body. Encouraging results have been obtained in animal studies using tumour cells modified to express cytokines e.g. interleukin 2 (IL-2), interleukin 4 (IL-4), granu-locyte-macrophage colony-stimulating factor (GM-CSF) and interferon (IFN) see Chapter 10 for further details (Tepper and Mule, 1994), co-stimulatory molecules (e.g. members...

Pharmacology and human toxicology of antimony drugs

No effective vaccine for Leishmania has yet been developed chemotherapy remains the only way at present of treating the disease. Dosage of antimony drugs is based on the amount of metal (antimony) administered per body weight. The early trial of treatment of visceral leishmaniasis by sodium stiboglu-conate was recommended to be 10 mg kg-1 day-1 for the period of 6-10 days. Despite a high cure rate, increasing resistance and relapses have been reported.44 46 Currently, the optimum overall dosage of the drug is roughly 20 mg kg-May-1 with maximum 850 mg of antimony per day for 20 30 days.47,48

Nucleic Acidbased Drugs

As described in the introduction to this chapter, nucleic acid-based therapeutics are attracting increasing interest. Gene replacement therapies and gene vaccines are no longer the only targets, as antisense oligonucleotides, which suppress or block expression of certain proteins, are now considered efficient and promising future therapeutics for clinical development. Currently, a number of DNA vaccines and oligonucleotides are in clinical trials for treatment of infectious diseases including AIDS HIV infections, different stages and types of cancer, cardiovascular and neurological diseases, as well as genetic deficiency disorders, and autoimmune and metabolic diseases (1,166). To date, however, few products have been approved, one being Vitravene (Ciba Vision Isis Pharmaceuticals), an injectable that was approved by Food and Drug Administration (FDA) in 1998 for the treatment of cytomegalovirus retinitis in patients with AIDS (1,2). However, the drug has currently the marketing...

Toxintargeted Constructs

The potential use of anthrax toxin as a delivery system aimed at antigen-presenting cells is most clearly demonstrated in the delivery of HIV gp120-derived peptides 131 . The N-ter-minal domain of LF was genetically fused to the gp120 portion of the HIV envelope protein. When administered in combination with recombinant PA, this construct elicited a specific cy-totoxic T-lymphocyte immune response towards the HIV gp120 protein. This study and others, in which other peptide epitopes were delivered to antigen-presenting cells, imply a general application for the anthrax toxin as a peptide vaccine delivery vehicle 129,139 .

Overview of Central Nervous System CNS Bacterial iNfECTioNs

Bacterial infections can be generally subdivided into two categories based on the anatomical location of lesions. Bacterial meningitis, as the name implies, involves infection of the subarachnoid space and can be caused by a wide array of organisms. Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae are among the leading etiologic agents of community-acquired meningitis in humans.12 Despite advances made in vaccination and treatment strategies, bacterial meningitis remains associated with a significant mortality rate and incidence of neurological sequelae, particularly in very young and elderly patients. Long-term effects resulting from meningitis include hearing loss, hydrocephalus, and sequelae associated with parenchymal damage including memory loss, cerebral palsy, learning disabilities, and seizures.34 Bacterial meningitis elicits a complex myriad of pathophysiological changes, many of which have been attributed to an excessive host antibacterial immune...

Perspective of the Market

The market for animal health products is often divided into two main areas pharmaceuticals and biologicals. In simple terms, pharmaceuticals are medicines to treat and cure animals, while biologicals are vaccines to prevent diseases. However, things can get muddled. Protein drugs like bovine growth hormone are not vaccines but often can be called a biological and may be classified as pharmaceuticals. Sometimes a third class is nutritionals, which cover products like selenium supplements for livestock or vitamins for companion animals. Medicinal and nutritional feed additives can be another designation. In addition there is the pet food and pesticide herbicide industries and their respective products. Therefore, it is important when examining sales figures for companies that an understanding of what is being reported is clear. For example, in 2001, the reported animal health market was 17 billion (this figure includes pharmaceuticals, biologicals, feed additives, and nutritionals) (1)....

Characteristic Production Processes

The development of eukaryotic cell culture for the production of vaccines has long been established in the pharmaceutical industry and an extensive database has been developed to ensure the suitability of such protein products in humans. The extension of this technology to rDNA products was primarily a response to the limitations in the use of E. coli. Particularly with respect to large proteins or glycoproteins, eukaryotic cell expression is an attractive alternative to a bacterial system because eukaryotic cells can secrete proteins that are properly folded and identical in primary, secondary, and tertiary structure to the natural human protein. Concerns about the economics of this production system orginally hindered its development. Recent advances, however, in improved expression levels, in large-scale cell culture using Chinese Hamster Ovary (CHO) cells, and in the formulation of more highly defined growth media have combined to dramatically improve the economic feasibility of...

Synthesis of Antigenic Glycoconjugates

The preparation of complex glycoconjugates has been a current strategy for the design of synthetic vaccines and usually involves the preparation of the oligosac-charide moiety, which provides the immune specificity by chemical or enzymatic methods, and further attachment through a linker with an immunogenic protein. There has been a continuous effort for developing glycoconjugates containing antigens such as MBrl antigen Globo-H, the blood group determinant and ovarian cancer antigen Lewisy, N3 antigens associated with gastrointestinal cancer, the adenocarcinoma antigen KH-1, and the small cell lung carcinoma antigen fucosyl GM1, among others (Figure 6.21), as promising alternatives to develop potentially useful carbohydrate-based anticancer vaccines accessible for clinical program. The synthetic approach becomes justified if we consider that cancer and normal cell growing in tissue culture generally show minimal level of expression of such antigens.72 It has been mentioned that...

Eukaryotic Cell Cultures

The origin of large-scale cell culture techniques for the production of biotechnology-derived products can be traced back to the vaccine industry. Developments such as large-scale cell suspension cultures using recombinant organisms that secrete the desired protein into the media have had a significant impact on biotechnology. Large glycosylated proteins in quantities sufficient for the marketplace can now be produced. The use of eukaryotic cell cultures, however, is complicated by issues such as genetic stability, protein folding, and culture conditions, including cell viability and growth rates. For example, the genetic stability of cell cultures cannot be addressed as readily as E. coli fermentations by techniques such as plasmid sequence analysis because the gene that codes for the product is incorporated into the cell genome and is not easily recovered. One alternative is peptide mapping of the expressed protein, which requires a resolution and sensitivity adequate to detect...

Antiviral Agents 6121 Viral Diseases

The immune system in the body may recognize the surface glycopro-teins on the virus. Antibodies are formed which encapsulate and expel the virus. Vaccination uses an attenuated or weakened form of the virus, which nevertheless stimulates the formation of the relevant antibodies. The immune system is then prepared to cope with an invasive attack from the 'wild-type' virus. The consequences of the immune reaction include the fever and rhinitis associated with viral infections.

Psychological Effects Of Immune Activation In Humans

We have recently used a double-blind prospective design to investigate the immediate and prolonged psychological and physiological effects of a specific viral infection in humans (Morag, Yirmiya, Lerer, & Morag, in press). Subjects were teenager girls who were vaccinated with live attenuated rubella virus. Based on analysis of levels of antibodies to rubella, subjects were divided into two groups An experimental group (n 60), comprised of subjects who were initially seronegative and were infected following vaccination, and a control group (n 180), comprised of subjects who were already immune to rubella before vaccination. Compared to control subjects, and to their own baseline, subjects from low socioeconomic status (SES) within the experimental group exhibited more severe depressed mood, as measured by the Children Depression Inventory (CDI) (Fig. 1). In addition, the same subjects exhibited more social and attention problems and delinquent behavior, as measured by the Achenbach...

Routes Of Parenteral Administration

Lying immediately under the skin is a layer of fat, the superficial fascia, which lends itself to safe administration of a great variety of drugs, including vaccines, insulin, scopolamine, and epinephrine. SC injections are usually administered in volumes up to 2 mL using - to 1-in. 23-gauge (or smaller) needles. Care must be taken to ensure that the needle is not in a blood vessel. This is done by lightly pulling back on the syringe plunger (aspiration) before making the injection. If the needle is inadvertently located in a blood vessel, blood will appear in the syringe, and the injection should not be made. The injection site may be massaged after injection, to facilitate drug absorption. Drugs given

Errare Humanum Est What Causes Cancer and How to Selectively Fight Tumors

Almost 400 biotech medicines are currently undergoing trials in the US, with the majority (close to 50 ) being directed against cancer in one or more of its many manifestations, and a significant number being directed towards infectious disease, autoimmune disease and HIV. A significant proportion of all materials in the cancer and infectious disease areas are vaccines of one type or another, and the second largest class of biopharmaceuticals under development are mAbs, with the largest numbers being directed towards cancer and autoimmune diseases. The authors demonstrate the current and future potential of the search in nature for biologically active peptides and proteins, and the ability to express these agents in homologous and or heterologous hosts. The ability to manipulate the gene sequences in order to produce subtle modifications of existing active agents and the potential for semisynthesis to modify the basic properties of the initial agents is amply demonstrated in the...

Cancer Prevention And Diet

In most human cancers, carcinogens are not so clearly defined that they can be eliminated or avoided. Even the carcinogens discussed in the previous section are not the only causes of the respective cancers. Thus, more careful exposure to sunlight will prevent many, but not all skin cancers. Vaccination against HBV (and eventually HCV) is expected to prevent liver cancers resulting from chronic viral

Methods to Assess Translocation

In a number of experimental situations it is desirable to translocate proteins from the exterior into the cytosol, and this may also be desirable for vaccination purposes. Since many proteins retain their function in fusion proteins, cDNA for the protein in question may be linked to the cDNA of a toxin A-moiety and, after expression and reconstitu-

Examples of Translocated Peptides and Proteins

It has been shown that a number of peptides linked to the N-terminal end of the diphtheria toxin A-fragment are translocated to the cytosol (Stenmark etal., 1991, Stenmark etal., 1992 Ariansen etal., 1993). It is an interesting question to what extent such peptides can subsequently be presented by class I major histocompatibility antigens. If this is the case, fusion proteins of viral or cancer-related peptides and enzymatically inactive mutants of diphtheria toxin could be used for vaccination purposes to expand desired populations of cytotoxic CD 8+ T-lymphocytes.

Prevention Of Cancers In Groups At High Risk

Recommending dietary changes such as 'Take 5 ' ( 20.3) is a cancer prevention strategy that addresses the overall population. This strategy is unproblematic. No adverse effects are to be feared and the same changes in diet supposed to decrease the risk of major cancers very likely diminish the risk of cardiovascular disease and diabetes, to a perhaps even greater extent. It is similarly unproblematic to pursue cancer prevention by vaccinating an entire population against HBV or HCV, which likewise has the additional benefit of preventing acute and chronic liver disease. There are risks involved in vaccination, since a few individual show adverse reactions, but they are much lower than the risks associated with actual infections. Moreover, as HBV does not seem to possess an animal reservoir, there is hope that this virus may not only be contained, but eventually be exterminated by vaccination. No foreseeable downside would be associated with its demise. A bit more problematic is the...

Additional virus vectors

Vaccinia virus and Pox virus vectors have been developed for the delivery of therapeutic genes for specific clinical purposes. Vaccinia virus vectors can accept large inserts of exogenous DNA (up to 25 kb) and have been used to deliver IL-1 sequences to tumour cells (21). Pox virus vectors can accept approximately 4 kb of exogenous DNA and have been used at the interface between gene therapy and vaccination due to their ability to infect human cells in the absence of viral replication (22).

Macrocyclic Lactones as Antiparasitic Agents in the Future

Two distinct questions come to mind when we ask how macrocyclic lactone antiparasitic agents (MLs) will be used in the future. First, what general role will anthelmintics and endectocides play in the future Secondly, and in that context, how will MLs be used Consideration of these broad questions can be focused by separately addressing future challenges to the use of chemotherapy for metazoan parasites (including MLs), and the opportunities for new or expanding applications of MLs, in contrast to new management, new vaccines, new drugs, etc., that may diminish ML markets.

Animal Models for Evaluation

To define the contribution of various mycobacterial genes to virulence or in studies of immunological responses to MTb infection, it does not reproduce the lung pathology observed in the human 290, 344 . However, the poor sterilizing activity of INH and the treatment-shortening effect of treating with INH, RIF, and PZA containing regimens in the mouse model are superficially similar to their efficacy in human studies hence, it is argued that the mouse model is predictive of human relapse rates 345 . Since the mouse does not develop the latent disease that characterizes the spectrum of human TB but rather develops a chronic disease marked by very high bacterial burdens and progressive destruction of lung tissue, it has been argued that this animal model is unsuitable for testing drugs under development for latent disease 362 . The development of the gamma interferon gene-disrupted C57BL6 mouse has shortened initial in vivo drug evaluation to about 2 weeks, but may only reflect drug...

Gene Therapy and Cancer

Immunomodulatory cancer gene therapy involves the production of autologous cellular vaccines by ex-vivo transduction of immunostimulatory molecules and their subsequent implantation to induce a systemic immune response aimed at tumour cell destruction, and vaccination against tumour recurrence (39). Immunological destruction of tumour cells in vivo has been reported after vaccination with cells that produce immune activating cytokines. Several phase I clinical trials involving autologous retrovirally modified tumour cells transduced with IL-2, TNFC and GM-CSF into melanoma, colorectal, renal cell carcinoma, neuroblastoma and breast cancer cells are underway (39). Another approach involves rendering tumour cells more immunogenic through the transduction of co-stimulatory molecules such as B7 which enhances T cell activation. While transfection with B7 inhibits tumour growth, covaccination with the cytokine IL-2 has been found to significantly enhance antitumour activity (46, 47). In...

Containment Facilities

The selection of an appropriate laboratory or biosafety level for a particular type of work hinges on a number of factors. Some of the more important of these factors are the potency and stability of the toxin being handled, the virulence and pathogenicity of the infectious agents being handled, and the availability of protective vaccines or therapeutic measures.

HSV1 Based Vectors Applications

HSV-1 Based Vectors for Vaccination Many of the HS V based vectors have been used in gene therapy studies and some of them as experimental vaccines against HS V-1 infection.26-8*'0 However, studies related to the evaluation of the potential of these vectors, as foreign gene or protein delivery systems for immunological studies are very limited. The use of HSV vectors requires the development of mutated viruses that are genetically stable, incapable of replicating in the CNS and of spreading in immunocompromised individuals, not transmissible from immunized individual by contacts and, at the same time, capable of inducing protective immunity against the disease. Recent major breakthroughs in the field of HSV-1 technology authorize and support the use of HSV-1 as vaccine vectors for the delivery of foreign antigens.89-91'95 In particular, HSV vectors show several advantages for prophylaxis against viral infections. They have been shown (i) to elicit strong and durable immune responses...

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