Evidence for viral virulence as a predominant factor limiting human immunodeficiency virus vaccine efficacy

Current strategies in human immunodeficiency virus type 1 (HIV-1) vaccine d evelopment are often based on the production of different vaccine antigens according to particular genetic clades of HIV-1 variants. To determine if v irus virulence or genetic distance had a greater impact on HIV-1 vaccine ef ficacy, we designed a series of heterologous chimeric simian/human immunode ficiency virus (SHIV) challenge experiments in HIV I subunit-vaccinated rhe sus macaques. Of a total of 22 animals, 10 nonimmunized animals served as c ontrols; the remainder were vaccinated with the CCR5 binding envelope of HI V-1(W6.1D). In the first study, heterologous challenge included two nonpath ogenic SHIV chimeras encoding the envelopes of the divergent clade B HIV-1( han2) and HIV-1(sf13) strains. In the second study, all immunized animals w ere rechallenged with SHIV89.6p, a virus closely related to the vaccine str ain but highly virulent. Protection from either of the divergent SHIVsf13 o r SHIVhan2 challenges was demonstrated in the majority of the vaccinated an imals. In contrast, upon challenge with the more related but virulent SHIV8 9.6p, protection was achieved in only one of the previously protected vacci nees, A secondary but beneficial effect of immunization on virus load and C D4(+) T-cell counts was observed despite failure to protect from infection. In addition to revealing different levels of protective immunity, these re sults suggest the importance of developing vaccine strategies capable of pr otecting from particularly virulent variants of HIV-1.