Protection against measles virus-induced encephalitis by anti-mimotope antibodies: the role of antibody affinity.

Synthetic peptides mimicking a conformational B-cell epitope (M2) of the measles virus fusion protein (MVF) were used for the immunization of BALB/c mice and the anti-peptide and anti-virus antibody titers induced were compared. Of the panel of tested peptides, a chimeric peptide consisting of two copies of a T-helper epitope (residues 288-302 of MVF) and one copy of the mimotope M2 (TTM2) and a multiple antigen peptide with eight copies of M2 (MAP-M2) induced the highest titers of anti-M2 and anti-MV antibodies. Furthermore, peptides TTM2 and MAP-M2 induced antibodies with highest affinity for the mimotope and highest avidity for measles virus. Immunization with the MAP-M2 construct induced high titers of high-affinity anti-M2 antibody despite the absence of a T-helper epitope, and lymphocyte proliferation data suggest that the addition of M2 to the MAP resulted in the generation of a structure capable of stimulating T-cell help. Sera with anti-M2 reactivity were pooled according to affinity values for binding to M2, and high- and low-affinity pools were tested for their ability to prevent MV-induced encephalitis in a mouse model. The high-affinity serum pool conferred protection in 100% of mice, whereas the lower affinity pool conferred protection to only 50% of animals. These results indicate the potential of mimotopes for use as synthetic peptide immunogens and highlight the importance of designing vaccines to induce antibodies of high affinity.