Peptide immunogens designed to enhance immune responses against human immunodeficiency virus (HIV) mutant strains: a plausible means of preventing viral persistence

A major problem impeding the development of an effective HIV-1 vaccine is the rapid antigenic variability that occurs throughout the viral genome but is most pronounced in the envelope ( env) gene and env gene products. The high number of errors made by the reverse transcriptase (RT) enzyme and the absence of an RT proofreading mechanism during HIV-1 replication leads to new antigenic variants that escape current immunological attack. In turn, accumulation of escape mutants leads to a persistent infection. It has been hypothesized through many means including mathematical modeling that preventing HIV persistence necessitates a vaccine that enhances immunity against a sufficiently large fraction of mutant stains. To this extent we have developed a 4 branched—and an 8 branched—multiple epitope immunogen (MEI) that in theory represent 6.7×10 7 and 1.8×10 16 envelope V3 loop sequences respectively. Both MEI constructs were recognized by antibodies in sera from AIDS and/or HIV-1 positive patients from South Africa and Puerto Rico. The immunogens also induced immune responses in MF1 mice and New Zealand White rabbits with the octameric MEI proving to be a more effective antigen. This data supports our hypothesis that synthetic peptides designed to represent the variable regions of HIV-1 envelope should induce immunity against a large quantity of mutant strains.