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Sci Rep. 2018 Jan 11;8(1):542. doi: 10.1038/s41598-017-18863-0.

Functional Antibody Response Against V1V2 and V3 of HIV gp120 in the VAX003 and VAX004 Vaccine Trials.

Author information

1
The Sackler Institute of Graduate Biomedical Sciences, NYU School of Medicine, New York, NY, 10016, USA.
2
Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
3
Department of Pathology, NYU School of Medicine, New York, NY, 10016, USA.
4
Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR, 97006, USA.
5
Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR, 97239, USA.
6
Global Solutions for Infectious Diseases, South San Francisco, CA, 94080, USA.
7
Department of Environment Medicine, NYU School of Medicine, New York, NY, 10016, USA.
8
Molsoft LLC, La Jolla, CA, 92037, USA.
9
Department of Biochemistry and Molecular Pharmacology, NYU School of Medicine, New York, NY, 10016, USA.
10
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.
11
Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. catarina.hioe@mssm.edu.
12
James J. Peters VA Medical Center, Bronx, NY, 10468, USA. catarina.hioe@mssm.edu.

Abstract

Immunization with HIV AIDSVAX gp120 vaccines in the phase III VAX003 and VAX004 trials did not confer protection. To understand the shortcomings in antibody (Ab) responses induced by these vaccines, we evaluated the kinetics of Ab responses to the V1V2 and V3 regions of gp120 and the induction of Ab-mediated antiviral functions during the course of 7 vaccinations over a 30.5-month period. Plasma samples from VAX003 and VAX004 vaccinees and placebo recipients were measured for ELISA-binding Abs and for virus neutralization, Ab-dependent cellular phagocytosis (ADCP), and Ab-dependent cellular cytotoxicity (ADCC). Ab responses to V1V2 and V3 peaked after 3 to 4 immunizations and declined after 5 to 7 immunizations. The deteriorating responses were most evident against epitopes in the underside of the V1V2 β-barrel and in the V3 crown. Correspondingly, vaccinees demonstrated higher neutralization against SF162 pseudovirus sensitive to anti-V1V2 and anti-V3 Abs after 3 or 4 immunizations than after 7 immunizations. Higher levels of ADCP and ADCC were also observed at early or mid-time points as compared with the final time point. Hence, VAX003 and VAX004 vaccinees generated V1V2- and V3-binding Abs and functional Abs after 3 to 4 immunizations, but subsequent boosts did not maintain these responses.

PMID:
29323175
PMCID:
PMC5765017
DOI:
10.1038/s41598-017-18863-0
[Indexed for MEDLINE]
Free PMC Article

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