Number of cases of 2 years cannot make good T-cell-independent antibody responses and cannot be vaccinated effectively with polysaccharide (PS) vaccines. An efficient way of overcoming this problem is to conjugate bacterial polysaccharides chemically to protein carriers (see Fig. 16.27). This carrier protein provides peptides that can be recognized by antigen-specific T cells, thus converting a T-cell-independent response into a T-cell-dependent antipolysaccharide antibody response. Using this approach, various conjugate vaccines have been developed against H. influenzae type b, an important cause of serious childhood chest infections and meningitis, and against N. meningitidis serogroup C, an important cause of meningitis, and these are now widely applied. The success of the latter vaccine in the United Kingdom is illustrated in Fig. 16.28, which shows that the incidence of meningitis C has been markedly reduced in comparison with meningitis B, against which there is currently no vaccine. Endemic meningitis B is due to diverse serogroup B strains, so an ideal vaccine would target the group B capsular polysaccharide. Unfortunately, group B polysaccharide is identical to some polysialyl polysaccharides on human cells, and is poorly immunogenic due to tolerance of these self antigens. Some strategies to chemically modify the group B polysaccharide for use in a conjugate vaccine have been considered, but a major focus in group B meningococcal vaccine development has been to instead direct immunity against noncapsular antigens, which will be generally effective against endemic disease.
16-28 Peptide-based vaccines can elicit protective immunity, but they require adjuvants and must be targeted to the appropriate cells and cell compartment to be effective.
Another vaccine-development strategy that does not require the whole organism, whether killed or attenuated, identifies the T-cell peptide epitopes that stimulate protective immunity. Candidate peptides can be identified in two ways: in one, overlapping peptides from immunogenic proteins are systematically synthesized and their ability to stimulate protective immunity is tested; alternatively, a reverse immunogenetic approach (see Section 16-15) can be used to predict potential peptide epitopes from a genome sequence. The latter approach has been applied to malaria by using the complete sequence of the Plasmodium falciparum genome. The starting point was the association between the human MHC class I molecule HLA-B53 and resistance to cerebral malaria, a relatively infrequent, but usually fatal, complication of infection by P. falciparum. It was thought that HLA-B53 might protect against cerebral malaria because it could present peptides that are particularly good at activating naive cytotoxic T lymphocytes. Peptides eluted from HLA-B53 frequently contain a proline as the second of their nine amino acids. On the basis of this information, reverse genetic analysis identified candidate protective peptides from four proteins of P. falciparum expressed in the early phase of hepatocyte infection—an important phase of infection to target in an effective immune response. One of the candidate peptides, from liver stage antigen-1, has been shown to be recognized by cytotoxic T cells when bound to HLA-B53 and may be a useful peptide for use in vaccination.