Vaccines based on proteins and peptides may be safer and if calculated based on many sequences, more broad-spectrum than those designed based on single strains. Physicochemical Property Consensus (PCPcon) alphavirus (AV) antigens from the B-domain of the E2 envelope protein were designed, synthesized recombinantly and shown to be immunogenic (i.e. sera after inoculation detected the antigen in dotspots and ELISA). Antibodies in sera after inoculation with B-region antigens based on individual AV species (eastern or Venezuelan equine encephalitis (EEEVcon, VEEVcon), or chikungunya (CHIKVcon) bound only their cognate protein, while those designed against multiple species (Mosaikcon and EVCcon) recognized all three serotype specific antigens. The VEEVcon and EEEVcon sera only showed antiviral activity against their related strains (in plaque reduction neutralization assays (PRNT50/80). Peptides designed to surface exposed areas of the E2-A-domain of CHIKVcon were added to CHIKVcon inocula to provide anti-CHIKV antibodies. EVCcon, based on three different alphavirus species, combined with E2-A-domain peptides from AllAVcon, a PCPcon of 24 diverse AV, generated broad spectrum, antiviral antibodies against VEEV, EEEV and CHIKV, AV with less than 35% amino acid identity to each other (>65% diversity). This is a promising start to a molecularly defined vaccine against all AV. Further study with these antigens can illuminate what areas are most important for a robust immune response, resistant to mutations in rapidly evolving viruses. The validated computational methods can also be used to design broad spectrum antigens against many other pathogen families.
Keywords: Chikungunya vaccine; Computational protein design; D-graph ofproperty distances; Encephalitic and arthralgic alphaviruses; Physicochemical property consensus; Recombinant protein vaccine; Structure based peptide design.
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