Comparative Evaluation of HIV-1 Neutralization in External Secretions and Sera of HIV-1-Infected Women



Qing Wei 1, Zina Moldoveanu 1, Wen-Qiang Huang 1, Rashada C Alexander 1, 2, Paul A Goepfert 3, Jiri Mestecky*, 1, 4, 5
1 University of Alabama at Birmingham, Department of Microbiology, Birmingham, AL, USA
2 National Institutes of Health, Office of Extramural Research, Bethesda, MD, USA
3 University of Alabama at Birmingham, Department of Medicine, Division of Infectious Disease, Birmingham, AL, USA
4 University of Alabama at Birmingham, Department of Medicine, Birmingham, AL, USA
5 Charles University, Department of Immunology and Microbiology, 1st School of Medicine, Prague, Czech Republic


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© Wei et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Microbiology, University of Alabama at Birmingham, BBRB 757, 845 19th Street South, Birmingham, AL 35294, USA; Tel: (205)-934-2225; Fax: (205)-934-3894; E-mail: mestecky@uab.edu


Abstract

Objectives:

Although human immunodeficiency virus type 1 (HIV-1)-specific antibodies are detectable in external secretions by ELISA and western blot (WB), the presence of HIV-1 neutralizing antibodies is difficult to evaluate due to the low levels of immunoglobulins (Ig) and the presence of humoral factors of innate immunity. The objective of this study was to determine virus neutralization activity and the relative contribution of HIV-1-specific antibodies of various isotypes to virus neutralization in serum/plasma samples, cervicovaginal lavages (CVL), and rectal lavages (RL).

Design:

Serum/plasma, CVL, and RL samples were examined by ELISA, WB and HIV-1 neutralization assays. Selected samples were Ig depleted and analyzed for virus neutralization.

Results:

IgG specific for three HIV-1 ENV antigens was detected in all serum/plasma samples, while IgA to at least one ENV glycoprotein was found at the low levels in 95% samples. Serum/plasma samples had the ability to neutralize at least one of three clade B and two clade C viruses. The neutralizing titers were reduced significantly or became undetectable after IgG removal. In corresponding CVL and RL, HIV-1 ENV-specific IgG antibodies were readily detected compared to IgA. Furthermore, IgG in CVL had greater ability than IgA to reduce virus infectivity. The difference in HIV-1 neutralization before and after Ig depletion was not observed in RL, implying that innate humoral factors were involved in anti-HIV-1 activity.

Conclusions:

Results demonstrate that HIV-1-specific neutralizing antibodies are almost exclusively of the IgG isotype in serum/plasma and CVL samples. HIV-1-specific binding antibodies detected in RL are not responsible for neutralization activity, suggesting that the antibody-mediated virus neutralization in external secretions should be verified by means of a selective depletion of Ig.

Keywords: HIV-1-specific antibodies, humoral innate factors, IgA, IgG, Ig depletion, virus neutralization..