Evidence for Viral Virulence as a Predominant Factor Limiting Human Immunodeficiency Virus Vaccine Efficacy

Petra Mooij,1 Willy M. J. M. Bogers,1 Herman Oostermeijer,1 Wim Koornstra,1 Peter J. F. Ten Haaft,1 Babs E. Verstrepen,1 Gert Van Der Auwera,2 and Jonathan L. Heeney1,*

Department of Virology, Biomedical Primate Research Center, 2280 GH Rijswijk, The Netherlands,1 and Department of Microbiology, Institute of Tropical Medicine, B2000 Antwerp, Belgium2

Received 30 April 1999/Accepted 21 January 2000

Journal of Virology, May 2000, p. 4017-4027, Vol. 74, No. 9

Current strategies in human immunodeficiency virus type 1 (HIV-1) vaccine development are often based on the production of different vaccine antigens according to particular genetic clades of HIV-1 variants. To determine if virus virulence or genetic distance had a greater impact on HIV-1 vaccine efficacy, we designed a series of heterologous chimeric simian/human immunodeficiency virus (SHIV) challenge experiments in HIV-1 subunit-vaccinated rhesus macaques. Of a total of 22 animals, 10 nonimmunized animals served as controls; the remainder were vaccinated with the CCR5 binding envelope of HIV-1W6.1D. In the first study, heterologous challenge included two nonpathogenic SHIV chimeras encoding the envelopes of the divergent clade B HIV-1han2 and HIV-1sf13 strains. In the second study, all immunized animals were rechallenged with SHIV89.6p, a virus closely related to the vaccine strain but highly virulent. Protection from either of the divergent SHIVsf13 or SHIVhan2 challenges was demonstrated in the majority of the vaccinated animals. In contrast, upon challenge with the more related but virulent SHIV89.6p, protection was achieved in only one of the previously protected vaccinees. A secondary but beneficial effect of immunization on virus load and CD4+ T-cell counts was observed despite failure to protect from infection. In addition to revealing different levels of protective immunity, these results suggest the importance of developing vaccine strategies capable of protecting from particularly virulent variants of HIV-1.