Broader cross-reactivity after conjugation of V3 based multiple antigen peptides to HBsAg

Vaccines against highly variable pathogens should elicite antibodies to a huge number of clinical isolates. For this purpose, new strategies to overcome the variability are needed. We have previously reported a useful method to conjugate multiple antigen peptides (MAPs) to carrier proteins. Also, we have suggested that these conjugates might enhance cross-reactivity in comparison to other synthetic structures. In this work, MAPs were synthesized and their respective conjugates to HBsAg were obtained. Two peptides from the V3 loop of HIV-1 were included in the MAPs as B cell epitopes because of their variability. Groups of mice were immunized and the immunogenicity and the level of cross-reaction to a panel of five heterologous V3 peptides were studied. Our results show that sera from mice immunized with MAPs coupled to HBsAg recognize a higher number of heterologous peptides (P < 0.05). This behavior was related neither to the immunogenicity nor the antigenicity of the synthetic structures. These results have important implications for the choice of better immunogens against variable epitopes.