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PLoS One. 2017 Feb 21;12(2):e0172524. doi: 10.1371/journal.pone.0172524. eCollection 2017.

Pre-existing neutralizing antibody mitigates B cell dysregulation and enhances the Env-specific antibody response in SHIV-infected rhesus macaques.

Author information

1
Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, United States of America.
2
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America.
3
Division of Infectious Diseases, Department of Medicine, University of Rochester Medical Center, Rochester, New York, United States of America.
4
Divsion of Allergy, Immunology & Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, New York, United States of America.
5
Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York, United States of America.
6
Lowance Center for Human Immunology and Division of Rheumatology, Department of Medicine, Emory University, Atlanta, Georgia, United States of America.

Abstract

Our central hypothesis is that protection against HIV infection will be powerfully influenced by the magnitude and quality of the B cell response. Although sterilizing immunity, mediated by pre-formed abundant and potent antibodies is the ultimate goal for B cell-targeted HIV vaccine strategies, scenarios that fall short of this may still confer beneficial defenses against viremia and disease progression. We evaluated the impact of sub-sterilizing pre-existing neutralizing antibody on the B cell response to SHIV infection. Adult male rhesus macaques received passive transfer of a sub-sterilizing amount of polyclonal neutralizing immunoglobulin (Ig) purified from previously infected animals (SHIVIG) or control Ig prior to intra-rectal challenge with SHIVSF162P4 and extensive longitudinal sampling was performed. SHIVIG treated animals exhibited significantly reduced viral load and increased de novo Env-specific plasma antibody. Dysregulation of the B cell profile was grossly apparent soon after infection in untreated animals; exemplified by a ≈50% decrease in total B cells in the blood evident 2-3 weeks post-infection which was not apparent in SHIVIG treated animals. IgD+CD5+CD21+ B cells phenotypically similar to marginal zone-like B cells were highly sensitive to SHIV infection, becoming significantly decreased as early as 3 days post-infection in control animals, while being maintained in SHIVIG treated animals, and were highly correlated with the induction of Env-specific plasma antibody. These results suggest that B cell dysregulation during the early stages of infection likely contributes to suboptimal Env-specific B cell and antibody responses, and strategies that limit this dysregulation may enhance the host's ability to eliminate HIV.

PMID:
28222180
PMCID:
PMC5319772
DOI:
10.1371/journal.pone.0172524
[Indexed for MEDLINE]
Free PMC Article

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