title: Cross-protection in NYVAC-HIV-1-immunized/HIV-2-challenged but not in NYVAC-HIV-2-immunized/SHIV-challenged rhesus macaques.
abstract: OBJECTIVE
  Immunization 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.
  
  
  METHODS
  Twenty-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 SHIV(HXB2) the other half was challenged with HIV-2SBL6669,. Protective 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. 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.
  
  
  CONCLUSIONS
  Further delineation of cross-reactive mechanisms may aid in the development of a broadly protective vaccine.
authors: Basic Research Laboratory, National Cancer Institute, Bethesda, Maryland 20892-5055, USA.
authors: L J
authors: LJ
authors: Patterson
authors: B
authors: B
authors: Peng
authors: A G
authors: AG
authors: Abimiku
authors: K
authors: K
authors: Aldrich
authors: L
authors: L
authors: Murty
authors: P D
authors: PD
authors: Markham
authors: V S
authors: VS
authors: Kalyanaraman
authors: W G
authors: WG
authors: Alvord
authors: J
authors: J
authors: Tartaglia
authors: G
authors: G
authors: Franchini
authors: M
authors: M
authors: Robert-Guroff
mesh_terms: D016915:AIDS Vaccines; D000818:Animals; D003429:Cross Reactions; D005260:Female; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015498:HIV-2 / Q000472:pathogenicity*; D007114:Immunization; D008253:Macaca mulatta; D008297:Male; D011212:Poxviridae / Q000235:genetics*; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D012367:RNA, Viral