Vaccines vaccine development

During the early 1900s, vaccines against major human epidemic diseases such as pertussis, diphtheria, tetanus, and tuberculosis were developed. Vaccines for many animal diseases were also available. In the early 1950s, the development of cell culture techniques byj. E. Enders at Harvard was followed by another series of major advances in vaccine development. Vaccines against poHo, mumps, measles, and mbeUa were Hcensed during the 1960s. 

Preventive medicine through vaccination continues to be the most cost-effective pubHc health practice, even with the drastic advance in modern medicine. Mass vaccination programs have eradicated smallpox from the earth. The World Health Organization (WHO) has a major campaign underway to eradicate poHo by the year 2000. The development of vaccines has saved millions of Hves and prevented many more from suffering. However, there are stiU many diseases without effective vaccines, such as malaria. With the recent emergence of antibiotic-resistance strains and exotic vimses, an effective vaccine development program becomes a top priority of pubHc health poHcy. 

Vaccines are used in either the general population of children or adults or for special groups. Recommendations for vaccine usage are made by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control. The Committee on Infectious Diseases of the American Academy of Pediatrics (Redbook Committee) also makes recommendations for infants through adolescents, and the American Academy of Family Physicians makes recommendations for adults. An excellent review of vaccine history, development, usage, and related regulatory issues is available (2). 

Rotavirus. Rotavims causes infant diarrhea, a disease which has major socio-economic impact. In developing countries it is the major cause of death in infants worldwide, causing up to 870,000 deaths per year. In the United States, diarrhea is stiU a primary cause of physician visits and hospitalization, although the mortaUty rate is relatively low. Studies have estimated a substantial cost benefit for a vaccination program in the United States (67—69). Two membrane proteins (VP4 and VP7) of the vims have been identified as protective epitopes and most vaccine development programs are based on these two proteins as antigens. Both Hve attenuated vaccines and subunit vaccines are being developed (68). 

Vaccine development is hampered by the fact that recurrent disease is common. Thus, natural infection does not provide immunity and the best method to induce immunity artificially is not clear. The genome of these vimses is also able to cause transformation of normal cells, thus conferring on them one of the properties attributed to cancerous cells. Vaccine made from herpes vimses must, therefore, be carefully purified and screened to eliminate the possibihty of including any active genetic material. 

Malaria. Malaria infection occurs in over 30% of the world s population and almost exclusively in developing countries. Approximately 150 X 10 cases occur each year, with one million deaths occurring in African children (87). The majority of the disease in humans is caused by four different species of the malarial parasite. Vaccine development is problematic for several reasons. First, the parasites have a complex life cycle. They are spread by insect vectors and go through different stages and forms (intercellular and extracellular sexual and asexual) as they grow in the blood and tissues (primarily fiver) of their human hosts. In addition, malaria is difficult to grow in large quantities outside the natural host (88). Despite these difficulties, vaccine development has been pursued for many years. An overview of the state of the art is available (89). 

Interest in vaccine development has centered around the asexual erothrocytic stage of the life cycle, especially the mero2oite. Several proteins associated with these stages have been identified and produced by recombinant techniques (92,93). The most prominent is the MSA-1 protein of the mero2oite. A clinical trial with this protein is being planned (93). 

Adjuvants are substances which can modify the immune response of an antigen (139,140). With better understanding of the functions of different arms of the immune system, it is possible to explore the effects of an adjuvant, such that the protective efficacy of a vaccine can be improved. At present, aluminum salt is the only adjuvant approved for use in human vaccines. New adjuvants such as QS-21, 3D-MPL, MF-59, and other liposome preparations are being evaluated. Several of these adjuvants have been in clinical trial, but none have been approved for human use. IL-12 has been proposed as an adjuvant which can specifically promote T-helper 1 ceU response, and can be a very promising adjuvant for future vaccine development. 

Alternatively, some subunit viral vaccines can be generated by rDNA techniques and expressed in a continuous ceU line or insect ceUs. Recent advances in bioreactor design and operation have improved the successful production of IPV in large-scale bioreactors. However, roUer bottles or flasks are stiU used for most current vaccine production. Development of insect ceU culture will allow for very large-scale Hquid suspension culture (143). Several vaccine candidates such as gpl60 for HIV and gD protein for herpes have been demonstrated in the insect ceU culture system. However, no vaccine has been approved for human use. 

MA M10 M10.056 Aeruginolysin Target for vaccine development, and chemotherapy of bacterial infection... 

MA M12 M12.133 Fibrolase (Agkistrodon contortrix) Potential target for vaccine development. 

An example of the use of an attenuated virus is the administration of the measles vaccine to an individual who has not had measles. The m easles (rubeola) vaccine contains the live, attenuated measles virus. The individual receiving the vaccine develops a mild or modified measles infection, which then produces immunity against the rubeola virus. The measles vaccine protects 95% of the recipients for several years or, for some individuals, for life. An example of a killed virus used for immunization is the cholera vaccine. This vaccine protects those who receive the vacdne for about 3 to 6 months. 

Rhyner C, Kundig X Akdis CA, Crameri R Targeting the MHC II presentation pathway in allergy vaccine development. Biochem Soc Trans 2007 35 74 833-834. 

A biomolecular system of glycoproteins derived from bacterial cell envelopes that spontaneously aggregates to form crystalline arrays in the mesoscopic range is reviewed in Chapter 9. The structure and features of these S-layers that can be applied in biotechnology, membrane biomimetics, sensors, and vaccine development are discussed. 

Grady C. Kelly G. (1996) HIV vaccine development. Nursing Clin North Am, 31, 25-39. 

Vaccines achieve their protective effects by stimulating a recipient s immune system to synthesize antibodies that promote the destruction of infecting microbes or neutralize bacterial toxins. This form of protection, known as active immunity, develops in the course of days and in the cases of many vaccines develops adequately only after two or three doses of vaccine have been given at intervals of days or weeks. Once established. 

There is the potential to develop a protective vaccine/immunization programme for each and every infectious disease. Whether or not such vaccines are developed and deployed is related to the severity and economic impact of the disease upon the eommunity as well as the effects upon the individual. Principles of immunity and of the produetion and quality control of immunological products are discussed in Chapters 14 and 15, respeetively. 

Nilsson, C. L. Bacterial proteomics and vaccine development. Am. J. Pharma-cogenomics 2002,2,59-65. 

The safety of the cocaine vaccine TC-CD in former cocaine abusers has been evaluated in a Phase I clinical trial, and it was determined that the vaccine was well tolerated with dose-related increases in antibody levels.65 Two Phase II clinical trials have now been conducted.66,67 The vaccine was again well tolerated and subjects reported a reduction in cocaine s reinforcing effects. The antibody levels were detectable after the second dose, peaked at 8 to 12 weeks, and remained elevated for up to 6 months preliminary findings indicated a negative association between antibody level and cocaine use. Other anti-cocaine vaccines in development include a blocking antibody (ITAC-cocaine) and a monoclonal catalytic antibody (15A10). 

Ferreira, L.C., Ferreira, R.C. and Schumann, W. (2005) Bacillus subtilis as a tool for vaccine development from antigen factories to delivery vectors. Anais da Academia Brasileira de Ciencias, 77 (1), 113-124. 

Zhao Z, Leong KW (1996) Controlled delivery of antigens and adjuvants in vaccine development. J Pharm Sci 85 1261-1270... 

Several plant vims coat proteins, including those of TMV, CPMV, AlMV and Tomato bushy stunt vims (TBSV), have been used to produce and deliver antigenic determinants from a variety of viral and bacterial pathogens. These data have been summarized in numerous publications and several reviews [12,13]. The ease of virus purification coupled with enhanced peptide immunogenicity when fused to carrier molecules makes this approach very attractive for vaccine development. 

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