Lj. Patterson et al., Cross-protection in NYVAC-HIV-1-immunized/HIV-2-challenged but not in NYVAC-HIV-2-immunized/SHIV-challenged rhesus macaques, AIDS, 14(16), 2000, pp. 2445-2455
Objectives: Immunization with attenuated poxvirus-HIV-1 recombinants follow
ed by protein boosting had protected four of eight rhesus macaques from HIV
-2(SBL6669) challenge. The present study was designed to confirm this resul
t and to conduct the reciprocal cross-protection experiment.
Methods: Twenty-four macaques were primed with NYVAC (a genetically attenua
ted Copenhagen vaccinia strain) recombinants with HIV-1 and HIV-2 env and g
ag-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 challe
nged with SHIVHXB2 the other half was challenged with HIV-2(SBL6669), Prote
ctive outcome was assessed by monitoring virus isolation, proviral DNA and
plasma viral RNA.
Results: Both 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. Significa
nt CD8AA was observed for only one NYVAC-HIV-2-immunized macaque. Virologic
al assessments verified that both NYVAC-HIV-1 and NYVAC-HIV-2 immunization
significantly reduced viral burdens and partially protected against HIV-2 c
hallenge, although cross-protection was not at the level that had been prev
iously reported. Humoral antibody and/or CTL and CD8AA were associated with
protection against homologous HIV-2 challenge, while cellular immune respo
nses seemed more important for cross-protection. No significant protection
was observed in the SHIV-challenged macaques, although NYVAC-HIV-1 immuniza
tion resulted in significantly lower viral burdens compared with controls.
Conclusions: Further delineation of cross-reactive mechanisms may aid in th
e development of a broadly protective vaccine. (C) 2000 Lippincott Williams
& Wilkins.