title: Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques.
abstract: HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Thus, some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses.
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Sampa
authors.initials: S
authors.lastname: Santra
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Warrier
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Nathan I
authors.initials: NI
authors.lastname: Nicely
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Justin
authors.initials: J
authors.lastname: Pollara
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Pinghuang
authors.initials: P
authors.lastname: Liu
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Ruijun
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Cocklin
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Shen
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Ryan
authors.initials: R
authors.lastname: Duffy
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Shi-Mao
authors.initials: SM
authors.lastname: Xia
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schutte
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Pemble Iv
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: S Moses
authors.initials: SM
authors.lastname: Dennison
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Chao
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Kora
authors.initials: K
authors.lastname: Vidnovic
authors.affiliation: Department of Medicine, St Mary's Campus, Imperial College London, London, United Kingdom.
authors.forename: Abbey
authors.initials: A
authors.lastname: Evans
authors.affiliation: Department of Medicine, St Mary's Campus, Imperial College London, London, United Kingdom.
authors.forename: Katja
authors.initials: K
authors.lastname: Klein
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Robinson
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California, Irvine, Irvine, California, United States of America.
authors.forename: Gary
authors.initials: G
authors.lastname: Landucci
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California, Irvine, Irvine, California, United States of America.
authors.forename: Donald N
authors.initials: DN
authors.lastname: Forthal
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Tropical Hygiene, Mahidol University, Bangkok, Thailand.
authors.forename: Jaranit
authors.initials: J
authors.lastname: Kaewkungwal
authors.affiliation: Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand.
authors.forename: Sorachai
authors.initials: S
authors.lastname: Nitayaphan
authors.affiliation: Clinical Tropical Medicine, 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: US Military Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.affiliation: US Military Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: US Military Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Soderberg
authors.affiliation: Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.
authors.forename: Elena E
authors.initials: EE
authors.lastname: Giorgi
authors.affiliation: Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.
authors.forename: Lily
authors.initials: L
authors.lastname: Blair
authors.affiliation: Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.
authors.forename: Bette T
authors.initials: BT
authors.lastname: Korber
authors.affiliation: U1109, INSERM University of Strasbourg, Strasbourg, Alsace, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Moog
authors.affiliation: Department of Medicine, St Mary's Campus, Imperial College London, London, United Kingdom.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Shattock
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Joern E
authors.initials: JE
authors.lastname: Schmitz
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: M A
authors.initials: MA
authors.lastname: Moody
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.affiliation: Duke Human Vaccine Institute, Duke School of Medicine, Durham, North Carolina, United States of America.
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005455:Fluorescent Antibody Technique; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007413:Intestinal Mucosa / Q000821:virology; D008253:Macaca mulatta; D011487:Protein Conformation; D012007:Rectum; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D020349:Surface Plasmon Resonance; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D014759:Viral Envelope Proteins