Minor components of a multi-envelope HIV vaccine are recognized by type-specific T-helper cells

HIV has thus far evaded control by vaccines, in part due to the high diversity among viral isolates. To effectively target HIV diversity, we propose that multi-envelope HIV vaccines should be designed. We hypothesize that minor components of complex envelope cocktail vaccines can be immunogenic and can thus elicit unique T-cell responses. To test our hypothesis, we first defined unique T-helper cell determinants on 1007 (clade B) and UG92005 (UG, clade D) gp140 envelope proteins delivered by DNA vaccination. Peptide-specific T-helper cell responses were then used as markers for type-specific immune activity. Results showed that type-specific responses could indeed be generated when an envelope protein was represented as only 1 part per 100 of the total vaccine. We also found that type-specific T-helper cell responses were elicited and sustained toward an envelope that appeared only once within a sequential prime/boost/boost regimen. Our results illustrate the flexibility and durability of immune responses toward individual components of mixed envelope vaccines and encourage the continued development of vaccine cocktails for the control of HIV.