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Human non-neutralizing HIV-1 envelope monoclonal antibodies limit the number of founder viruses during SHIV mucosal infection in rhesus macaques

Journal Article · · PLoS Pathogens
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  1. Harvard Medical School, Boston, MA (United States)
  2. Duke School of Medicine, Durham, NC (United States)
  3. Univ. of Pennsylvania, Philadelphia, PA (United States)
  4. Imperial College London, London (United Kingdom)
  5. Tulane Univ. School of Medicine, New Orleans, LA (United States)
  6. Univ. of California, Irvine, CA (United States)
  7. Mahidol Univ., Bangkok (Thailand)
  8. Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok (Thailand)
  9. Ministry of Public Health, Nonthaburi (Thailand)
  10. Walter Reed Army Institute of Research, Silver Springs, MD (United States)
  11. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  12. INSERM Univ. of Strasbourg, Alsace (France)
  13. Vaccine Research Center, Bethesda, MD (United States)
+ Show Author Affiliations
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. 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.
Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Grant/Contract Number:
AC52-06NA25396
OSTI ID:
1222591
Alternate ID(s):
OSTI ID: 1245848
Journal Information:
PLoS Pathogens, Journal Name: PLoS Pathogens Journal Issue: 8 Vol. 11; ISSN 1553-7374
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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  • The Journal of Infectious Diseases, Vol. 201, Issue 11 https://doi.org/10.1086/652702
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Cited By (5)

Envelope residue 375 substitutions in simian–human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques journal May 2016
Optimized Mucosal Modified Vaccinia Virus Ankara Prime/Soluble gp120 Boost HIV Vaccination Regimen Induces Antibody Responses Similar to Those of an Intramuscular Regimen journal May 2019
HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis journal January 2018
IgG3 enhances neutralization potency and Fc effector function of an HIV V2-specific broadly neutralizing antibody journal December 2019
Concurrent Exposure of Neutralizing and Non-neutralizing Epitopes on a Single HIV-1 Envelope Structure journal July 2019

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HIV-1
T cells
antibodies
enzyme-linked immunoassays
macaque
macrophages
rhesus monkeys
virions