Multivalent vaccines

Refer to Exhibits 3.7 and 4.2 for an explanation of the roles of hemagglutinin and neuraminidase, followed by the nomenclature for classifying influenza virus and the procedure that the FDA and WFIO recommend for the preparation of multivalent vaccines. 

It is thought likely that up to 30 extra genes can be incorporated into vaccinia. The upper capacity has not been determined, but is likely to exceed 50 kb. This facilitates the development of a multivalent vaccine via expression of several pathogen-derived genes in the recombinant virus. 

In the case of multivalent vaccines, the antibodies to all valencies are normally assayed. 

S. pneumoniae has more than 80 sero-types. The current polysaccharide vaccine consists of 23 serotypes and covers about 87% of all pneumococcal diseases in the United States. Current vaccine development is based on conjugate technology and concentrates on die most prevalent 7-9 serotypes. Three multivalent vaccine candidates are in clinical trials. All are based on conjugating the polysaccharide to a T-dependent protein carrier. The results of phase 1 and 11 trials in infants have demonstrated the safety and immnnogenicity of these vaccines. Phase. Ill trials to demonstrate efficacy are in progress and final approval of this vaccine for infant immunization will be by the year 2000. 

A good example of the recent and future evolution of viral vaccines and their concomitant issues of technology, complexity and competition, is the rotavirus vaccine. This is of great relevance for the prevention of diarrhea, which is often deadly in developing countries (half a million deaths per year) and has high hospitalization costs in rich countries. After successive failures of monovalent vaccines, multivalent vaccines based on the reshuffling of rotavirus strains comprising the attenuation properties of animal strains with the external capsid of human serotypes were developed. 

It is our belief that the ideal vaccines of the future will be constituted by synthetic peptide antigens, carbohydrates, and lipids. Because of the complexity of human T cells, it is also likely that several T-cell peptide epitopes would be required to create a vaccine that is able to induce a universal protective immune response. As vaccination of infants in developing countries is not a simple task, multivalent vaccines or cocktails of vaccines are highly recommended. 

Table 3 has also summarized some TACA-hased semisynthetic multivalent conjugate vaccines in clinical stages, which are mainly polyvalent monomeric vaccines, as well as their immune responses and therapeutic effects in certain cancers. No semisynthetic unimolecular multivalent vaccine has reached clinical trials so far. 

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