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HIV-1 subtype C superinfected individuals mount low autologous neutralizing antibody responses prior to intrasubtype superinfection

Debby Basu13, Colleen S Kraft2, Megan K Murphy13, Patricia J Campbell4, Tianwei Yu5, Peter T Hraber6, Carmela Irene7, Abraham Pinter7, Elwyn Chomba8, Joseph Mulenga8, William Kilembe8, Susan A Allen2589, Cynthia A Derdeyn23 and Eric Hunter1023*

Author Affiliations

1 Immunology and Molecular Pathogenesis Graduate Program, Emory University, Atlanta, GA, USA

2 Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA

3 Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA

4 Emory University, Atlanta, Georgia, USA

5 Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA

6 Los Alamos National Laboratory, Los Alamos, New Mexico, USA

7 Public Health Research Institute Center, New Jersey Medical School, Newark, UMDNJ, New Jersey, USA

8 Zambia Emory HIV Research Project, Lusaka, Zambia

9 Projet San Francisco, Kigali, Rwanda

10 Department of Pathology, Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, Georgia, 30329, USA

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Retrovirology 2012, 9:76  doi:10.1186/1742-4690-9-76

Published: 20 September 2012

Abstract

Background

The potential role of antibodies in protection against intra-subtype HIV-1 superinfection remains to be understood. We compared the early neutralizing antibody (NAb) responses in three individuals, who were superinfected within one year of primary infection, to ten matched non-superinfected controls from a Zambian cohort of subtype C transmission cases. Sequence analysis of single genome amplified full-length envs from a previous study showed limited diversification in the individuals who became superinfected with the same HIV-1 subtype within year one post-seroconversion. We hypothesized that this reflected a blunted NAb response, which may have made these individuals more susceptible to superinfection.

Results

Neutralization assays showed that autologous plasma NAb responses to the earliest, and in some cases transmitted/founder, virus were delayed and had low to undetectable titers in all three superinfected individuals prior to superinfection. In contrast, NAbs with a median IC50 titer of 1896 were detected as early as three months post-seroconversion in non-superinfected controls. Early plasma NAbs in all subjects showed limited but variable levels of heterologous neutralization breadth. Superinfected individuals also exhibited a trend toward lower levels of gp120- and V1V2-specific IgG binding antibodies but higher gp120-specific plasma IgA binding antibodies.

Conclusions

These data suggest that the lack of development of IgG antibodies, as reflected in autologous NAbs as well as gp120 and V1V2 binding antibodies to the primary infection virus, combined with potentially competing, non-protective IgA antibodies, may increase susceptibility to superinfection in the context of settings where a single HIV-1 subtype predominates.

Keywords:
HIV-1 superinfection; Subtype C; Neutralizing antibodies; HIV-1 transmission; HIV-1 dual infection