title: Evidence for viral virulence as a predominant factor limiting human immunodeficiency virus vaccine efficacy.
abstract: 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-1(W6.1D). In the first study, heterologous challenge included two nonpathogenic 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 were rechallenged with SHIV(89. 6p), a virus closely related to the vaccine strain but highly virulent. Protection from either of the divergent SHIV(sf13) or SHIV(han2) challenges was demonstrated in the majority of the vaccinated animals. In contrast, upon challenge with the more related but virulent SHIV(89.6p), 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.
authors.affiliation: Department of Virology, Biomedical Primate Research Center, 2280 GH Rijswijk, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Mooij
authors.forename: W M
authors.initials: WM
authors.lastname: Bogers
authors.forename: H
authors.initials: H
authors.lastname: Oostermeijer
authors.forename: W
authors.initials: W
authors.lastname: Koornstra
authors.forename: P J
authors.initials: PJ
authors.lastname: Ten Haaft
authors.forename: B E
authors.initials: BE
authors.lastname: Verstrepen
authors.forename: G
authors.initials: G
authors.lastname: Van Der Auwera
authors.forename: J L
authors.initials: JL
authors.lastname: Heeney
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D004195:Disease Models, Animal; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000235:genetics; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D008253:Macaca mulatta; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D014613:Vaccines, Attenuated / Q000276:immunology; D014774:Virulence
chemical_list: D016915:AIDS Vaccines; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D014613:Vaccines, Attenuated