title: Boosting of ALVAC-SIV Vaccine-Primed Macaques with the CD4-SIVgp120 Fusion Protein Elicits Antibodies to V2 Associated with a Decreased Risk of SIVmac251 Acquisition.
abstract: The recombinant ALVAC vaccine coupled with the monomeric gp120/alum protein have decreased the risk of HIV and SIV acquisition. Ab responses to the V1/V2 regions have correlated with a decreased risk of virus acquisition in both humans and macaques. We hypothesized that the breadth and functional profile of Abs induced by an ALVAC/envelope protein regimen could be improved by substituting the monomeric gp120 boost, with the full-length single-chain (FLSC) protein. FLSC is a CD4-gp120 fusion immunogen that exposes cryptic gp120 epitopes to the immune system. We compared the immunogenicity and relative efficiency of an ALVAC-SIV vaccine boosted either with bivalent FLSC proteins or with monomeric gp120 in alum. FLSC was superior to monomeric gp120 in directing Abs to the C3 α2 helix, the V5 loop, and the V3 region that contains the putative CCR5 binding site. In addition, FLSC boosting elicited significantly higher binding Abs to V2 and increased both the Ab-dependent cellular cytotoxicity activity and the breadth of neutralizing Abs. However, the FLSC vaccine regimen demonstrated only a trend in vaccine efficacy, whereas the monomeric gp120 regimen significantly decreased the risk of SIVmac251 acquisition. In both vaccine regimens, anti-V2 Abs correlated with a decreased risk of virus acquisition but differed with regard to systemic or mucosal origin. In the FLSC regimen, serum Abs to V2 correlated, whereas in the monomeric gp120 regimen, V2 Abs in rectal secretions, the site of viral challenge, were associated with efficacy.
authors: Animal Models and Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors: Shari N
authors: 0000-0001-6715-7334
authors: SN
authors: Gordon
authors: Animal Models and Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors: Namal P M
authors: 0000-0001-7362-3282
authors: NP
authors: Liyanage
authors: Animal Models and Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors: Melvin N
authors: MN
authors: Doster
authors: Animal Models and Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors: Monica
authors: M
authors: Vaccari
authors: Immune Biology of Retroviral Infection Section, Vaccine Branch, National Cancer Institute, Bethesda, MD 20892;
authors: Diego A
authors: 0000-0001-7405-9572
authors: DA
authors: Vargas-Inchaustegui
authors: Animal Models and Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors: Poonam
authors: 0000-0001-7926-3118
authors: P
authors: Pegu
authors: Animal Models and Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors: Luca
authors: L
authors: Schifanella
authors: Duke University Medical Center, Durham, NC 27710;
authors: Xiaoying
authors: X
authors: Shen
authors: Duke University Medical Center, Durham, NC 27710;
authors: Georgia D
authors: 0000-0001-8076-1931
authors: GD
authors: Tomaras
authors: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910;
authors: Mangala
authors: 0000-0001-9553-4969
authors: M
authors: Rao
authors: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910;
authors: Erik A
authors: 0000-0002-8963-0484
authors: EA
authors: Billings
authors: Profectus BioSciences Inc., Baltimore, MD 21224;
authors: Jennifer
authors: 0000-0001-8239-8857
authors: J
authors: Schwartz
authors: Profectus BioSciences Inc., Baltimore, MD 21224;
authors: Ilia
authors: I
authors: Prado
authors: Profectus BioSciences Inc., Baltimore, MD 21224;
authors: Kathryn
authors: K
authors: Bobb
authors: Profectus BioSciences Inc., Baltimore, MD 21224;
authors: Wenlei
authors: W
authors: Zhang
authors: Duke University Medical Center, Durham, NC 27710;
authors: David C
authors: 0000-0003-0856-6319
authors: DC
authors: Montefiori
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
authors: Kathryn E
authors: KE
authors: Foulds
authors: Duke University Medical Center, Durham, NC 27710;
authors: Guido
authors: 0000-0001-7747-3349
authors: G
authors: Ferrari
authors: Immune Biology of Retroviral Infection Section, Vaccine Branch, National Cancer Institute, Bethesda, MD 20892;
authors: Marjorie
authors: M
authors: Robert-Guroff
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
authors: Mario
authors: 0000-0001-7448-7040
authors: M
authors: Roederer
authors: Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine, CA 92868;
authors: Tran B
authors: TB
authors: Phan
authors: Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine, CA 92868;
authors: Donald N
authors: DN
authors: Forthal
authors: The Emmes Corporation, Rockville, MD 20850;
authors: Donald M
authors: DM
authors: Stablein
authors: Sanofi Pasteur, Swiftwater, PA 18370; and.
authors: Sanjay
authors: S
authors: Phogat
authors: Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors: David J
authors: 0000-0002-8990-158X
authors: DJ
authors: Venzon
authors: Profectus BioSciences Inc., Baltimore, MD 21224;
authors: Timothy
authors: 0000-0002-2429-2859
authors: T
authors: Fouts
authors: Animal Models and Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; franchig@mail.nih.gov.
authors: Genoveffa
authors: 0000-0001-5171-9849
authors: G
authors: Franchini
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D015704:CD4 Antigens / Q000737:chemistry / Q000276:immunology*; D002460:Cell Line; D015686:Gene Products, env / Q000737:chemistry / Q000276:immunology*; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: C078788:ALVAC vaccine; D000914:Antibodies, Viral; D015704:CD4 Antigens; D015686:Gene Products, env; D018449:SAIDS Vaccines; D014765:Viral Vaccines