Cross-protection in NYVAC–HIV-1-immunized/HIV-2-challenged but not in NYVAC–HIV-2-immunized/SHIV-challenged rhesus macaques


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Abstract

ObjectivesImmunization with attenuated poxvirus-HIV-1 recombinants followed by protein boosting had protected four of eight rhesus macaques from HIV-2SBL6669 challenge. The present study was designed to confirm this result and to conduct the reciprocal cross-protection experiment.MethodsTwenty-four macaques were primed with NYVAC (a genetically attenuated Copenhagen vaccinia strain) recombinants with HIV-1 and HIV-2 env and gag–pol or NYVAC vector alone and boosted with homologous, oligomeric gp160 proteins or adjuvant only. Binding and neutralizing antibodies, cytotoxic T-lymphocytes (CTL) and CD8 T cell antiviral activity (CD8AA) were evaluated. One half of each immunization and control group were intravenously challenged with SHIVHXB2 the other half was challenged with HIV-2SBL6669,. Protective outcome was assessed by monitoring virus isolation, proviral DNA and plasma viral RNA.ResultsBoth immunization groups developed homologous binding antibodies; however, homologous neutralizing antibodies were only observed in NYVAC–HIV-2-immunized macaques. While no cross-reactive neutralizing antibodies were detected, both immunization groups displayed cross-reactive CTL. Significant CD8AA was observed for only one NYVAC–HIV-2-immunized macaque. Virological assessments verified that both NYVAC–HIV-1 and NYVAC–HIV-2 immunization significantly reduced viral burdens and partially protected against HIV-2 challenge, although cross-protection was not at the level that had been previously reported. Humoral antibody and/or CTL and CD8AA were associated with protection against homologous HIV-2 challenge, while cellular immune responses seemed more important for cross-protection. No significant protection was observed in the SHIV-challenged macaques, although NYVAC–HIV-1 immunization resulted in significantly lower viral burdens compared with controls.ConclusionsFurther delineation of cross-reactive mechanisms may aid in the development of a broadly protective vaccine.

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