title: Tissue memory B cell repertoire analysis after ALVAC/AIDSVAX B/E gp120 immunization of rhesus macaques.
abstract: The ALVAC prime/ALVAC + AIDSVAX B/E boost RV144 vaccine trial induced an estimated 31% efficacy in a low-risk cohort where HIV‑1 exposures were likely at mucosal surfaces. An immune correlates study demonstrated that antibodies targeting the V2 region and in a secondary analysis antibody-dependent cellular cytotoxicity (ADCC), in the presence of low envelope-specific (Env-specific) IgA, correlated with decreased risk of infection. Thus, understanding the B cell repertoires induced by this vaccine in systemic and mucosal compartments are key to understanding the potential protective mechanisms of this vaccine regimen. We immunized rhesus macaques with the ALVAC/AIDSVAX B/E gp120 vaccine regimen given in RV144, and then gave a boost 6 months later, after which the animals were necropsied. We isolated systemic and intestinal vaccine Env-specific memory B cells. Whereas Env-specific B cell clonal lineages were shared between spleen, draining inguinal, anterior pelvic, posterior pelvic, and periaortic lymph nodes, members of Env‑specific B cell clonal lineages were absent in the terminal ileum. Env‑specific antibodies were detectable in rectal fluids, suggesting that IgG antibodies present at mucosal sites were likely systemically produced and transported to intestinal mucosal sites.
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Kan
authors.initials: K
authors.lastname: Luo
authors.affiliation: Duke Human Vaccine Institute.|Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.|College of Life Science and Technology, Jinan University, Guangzhou, China.
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Ruijun
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: David
authors.initials: D
authors.lastname: Easterhoff
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Kevin
authors.initials: K
authors.lastname: Wiehe
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Thaddeus C
authors.initials: TC
authors.lastname: Gurley
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Armand
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Allen
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Tarra A
authors.initials: TA
authors.lastname: Von Holle
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Dawn J
authors.initials: DJ
authors.lastname: Marshall
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: John F
authors.initials: JF
authors.lastname: Whitesides
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Jamie
authors.initials: J
authors.lastname: Pritchett
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Andrew
authors.initials: A
authors.lastname: Foulger
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Hernandez
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Robert
authors.initials: R
authors.lastname: Parks
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Krissey E
authors.initials: KE
authors.lastname: Lloyd
authors.affiliation: Duke Human Vaccine Institute.
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authors.initials: C
authors.lastname: Stolarchuk
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Sheetal
authors.initials: S
authors.lastname: Sawant
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Jessica
authors.initials: J
authors.lastname: Peel
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Yates
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Erika
authors.initials: E
authors.lastname: Dunford
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Arora
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Amy
authors.initials: A
authors.lastname: Wang
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Cindy M
authors.initials: CM
authors.lastname: Bowman
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Sutherland
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Scearce
authors.affiliation: Duke Human Vaccine Institute.
authors.forename: Shi-Mao
authors.initials: SM
authors.lastname: Xia
authors.affiliation: Duke Human Vaccine Institute.|Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Mattia
authors.initials: M
authors.lastname: Bonsignori
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Pollara
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: R Whitney
authors.initials: RW
authors.lastname: Edwards
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Sampa
authors.initials: S
authors.lastname: Santra
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.affiliation: Sanofi-Pasteur, Swiftwater, Pennsylvania, USA.
authors.forename: James
authors.initials: J
authors.lastname: Tartaglia
authors.affiliation: Global Solutions for Infectious Diseases, South San Francisco, California, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Francis
authors.affiliation: Global Solutions for Infectious Diseases, South San Francisco, California, USA.
authors.forename: Faruk
authors.initials: F
authors.lastname: Sinangil
authors.affiliation: Global Solutions for Infectious Diseases, South San Francisco, California, USA.
authors.forename: Carter
authors.initials: C
authors.lastname: Lee
authors.affiliation: Center of Excellence for Biomedical and Public Health Informatics BIOPHICS, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Jaranit
authors.initials: J
authors.lastname: Kaewkungwal
authors.affiliation: Armed Forces Research Institute of Medical Sciences-Royal Thai Army Component, Bangkok, Thailand.
authors.forename: Sorachai
authors.initials: S
authors.lastname: Nitayaphan
authors.affiliation: Mahidol University, Bangkok, Thailand.
authors.forename: Punnee
authors.initials: P
authors.lastname: Pitisuttithum
authors.affiliation: Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: Supachai
authors.initials: S
authors.lastname: Rerks-Ngarm
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Duke Human Vaccine Institute.|Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.|Department of Pathology.
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.affiliation: Duke Human Vaccine Institute.|Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Vandergrift
authors.affiliation: Duke Human Vaccine Institute.|Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Duke Human Vaccine Institute.|Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.|Department of Immunology.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Duke Human Vaccine Institute.|Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.|Department of Immunology.
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.affiliation: Duke Human Vaccine Institute.|Department of Immunology.|Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
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authors.initials: MA
authors.lastname: Moody
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000145:classification*; D015483:HIV Antibodies / Q000032:analysis; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control*; D018928:Immunity, Mucosal; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000032:analysis; D008253:Macaca mulatta
chemical_list: D016915:AIDS Vaccines; C112734:AIDSVAX; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G