Immune responses in mice following immunization with chimeric synthetic peptides representing B and T cell epitopes of measles virus proteins

Abstract

The immunogenicity of chimeric peptides produced by collinear synthesis to contain both T and B cell epitopes from the fusion protein and the haemagglutinin of measles virus was studied in mice. The T cell epitope used was from the fusion protein (residues 288 to 302), which has been shown to be promiscuous in its binding to mouse major histocompatibility complex molecules. This epitope was coupled by (i) a glycine-glycine spacer to a B cell epitope from the fusion protein (residues 404 to 414) and (ii) either its amino or carboxy terminus to a neutralizing antibody epitope from the haemagglutinin (residues 188 to 199). The results obtained show that such chimeric peptides can indeed function as complete immunogens in a range of mouse strains of different H-2 haplotype, and can induce the production of antibodies which bind to the fusion protein and to measles virus. Furthermore, it was shown that the orientation of the T cell epitope with respect to the B cell epitope had a significant effect upon the immunogenicity and antigenic specificity of the chimera. This work gives further support to the concept of rationally designed synthetic peptide vaccines.

Heterogeneity of linear B cell epitopes of the measles virus fusion protein reacting with late convalescent sera

“…Other putative internal sequences showed little or no reactivity (peptides 30, 31, 61 to 63, 67, 71 and 96 to 98). In mice, peptide 52 induced antibodies, but these were not neutralizing [Partidos et al (1991) and our own results]. Like this T cell epitope described by Partidos and colleagues (Partidos & Steward, 1990;Partidos et al, 1991), other hidden sequences are also unlikely to be neutralizing.…”

Fine specificity of the antibody response to a synthetic peptide from the fusion protein and protection against measles virus-induced encephalitis in a mouse model.

“…In our previous studies we have shown that the lack of immunogenicity of the 404-414 peptide can be overcome by the addition of a T-helper epitope (Partidos et al, 1991).…”

“…In previous studies, it has been demonstrated that a region represented by residues 404-414 is an important B-cell epitope. Anti-404-414 antibodies were shown to be reactive with MV in several strains of mice (Partidos et al, 1991), and confer protection in a mouse encephalitis model after collinear synthesis at the carboxyl terminus of two copies of a T-helper epitope (Obeid et al, 1995).…”

“…Mice were bled at weekly intervals and serum samples were stored at k20 mC. At the end of the experiment (17 weeks after priming), mice were killed and pooled splenocytes from each group were tested for proliferative responses (as described previously ; Partidos et al, 1991) upon in vitro restimulation with various concentrations of 397-420 peptide or heat inactivated MV.…”

“…The sequence 397-420 was selected on the basis of (Partidos et al, 1991), (ii) it contains the region 404-414 previously identified as a B-cell epitope (Partidos et al, 1991) and shown to confer protection in the mouse MV-induced encephalitis model when linked to two copies of a T-helper epitope (Obeid et al, 1995), and (iii) this region from the F protein of the related Sendai virus contains a neutralizing epitope (Portner et al, 1987). In addition, the protective capacity of 397-420 peptide was tested against challenge with a neuroadapted strain of MV in C57BL\6 mice and BALB\c mice.…”