title: Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV.
abstract: A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a nonhuman primate challenge model with simian immunodeficiency virus (SIV). We show that antibodies to the SIV envelope are necessary and sufficient to prevent infection. Moreover, sequencing of viruses from breakthrough infections revealed selective pressure against neutralization-sensitive viruses; we identified a two-amino-acid signature that alters antigenicity and confers neutralization resistance. A similar signature confers resistance of human immunodeficiency virus (HIV)-1 to neutralization by monoclonal antibodies against variable regions 1 and 2 (V1V2), suggesting that SIV and HIV share a fundamental mechanism of immune escape from vaccine-elicited or naturally elicited antibodies. These analyses provide insight into the limited efficacy seen in HIV vaccine trials.
authors.affiliation: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.affiliation: SAIC-Frederick, Frederick National Laboratory, NIH, Frederick, Maryland 21702, USA.
authors.forename: Brandon F
authors.initials: BF
authors.lastname: Keele
authors.affiliation: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Schmidt
authors.affiliation: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Rosemarie D
authors.initials: RD
authors.lastname: Mason
authors.affiliation: 1] Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA [2] George Washington University, Washington DC 20052, USA.
authors.forename: Hugh C
authors.initials: HC
authors.lastname: Welles
authors.affiliation: Los Alamos National Laboratories, Los Alamos, New Mexico 87545, USA.
authors.forename: Will
authors.initials: W
authors.lastname: Fischer
authors.affiliation: Department of Surgery, Duke University, Durham, North Carolina 27710, USA.
authors.forename: Celia
authors.initials: C
authors.lastname: Labranche
authors.affiliation: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Foulds
authors.affiliation: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Mark K
authors.initials: MK
authors.lastname: Louder
authors.affiliation: 1] Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA [2] Sanofi-Pasteur, Cambridge, Massachusetts 02139, USA.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Yang
authors.affiliation: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA.
authors.forename: John-Paul M
authors.initials: JP
authors.lastname: Todd
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Buzby
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
authors.forename: Linh V
authors.initials: LV
authors.lastname: Mach
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Shen
authors.affiliation: Human Vaccine Institute, Duke University, Durham, North Carolina 27710, USA.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Seaton
authors.affiliation: Department of Surgery, Duke University, Durham, North Carolina 27710, USA.
authors.forename: Brandy M
authors.initials: BM
authors.lastname: Ward
authors.affiliation: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Bailer
authors.affiliation: Fred Hutchison Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: Raphael
authors.initials: R
authors.lastname: Gottardo
authors.affiliation: Biostatistics Research Branch, NIAID, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Gu
authors.affiliation: Department of Surgery, Duke University, Durham, North Carolina 27710, USA.
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.affiliation: Human Vaccine Institute, Duke University, Durham, North Carolina 27710, USA.
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.affiliation: Human Vaccine Institute, Duke University, Durham, North Carolina 27710, USA.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Denny
authors.affiliation: Department of Surgery, Duke University, Durham, North Carolina 27710, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Human Vaccine Institute, Duke University, Durham, North Carolina 27710, USA.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Los Alamos National Laboratories, Los Alamos, New Mexico 87545, USA.
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.affiliation: Biostatistics Research Branch, NIAID, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Martha C
authors.initials: MC
authors.lastname: Nason
authors.affiliation: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Seder
authors.affiliation: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.affiliation: 1] Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA [2].
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.affiliation: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Srinivas S
authors.initials: SS
authors.lastname: Rao
authors.affiliation: 1] Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA [2] Sanofi-Pasteur, Cambridge, Massachusetts 02139, USA.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
authors.affiliation: Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D018703:Founder Effect; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology*; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion / Q000276:immunology; D008253:Macaca mulatta; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D012306:Risk; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D018449:SAIDS Vaccines; D054299:env Gene Products, Human Immunodeficiency Virus