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. 2017 Apr:18:216-224.
doi: 10.1016/j.ebiom.2017.04.005. Epub 2017 Apr 7.

Comprehensive Characterization of Humoral Correlates of Human Immunodeficiency Virus 1 Superinfection Acquisition in High-risk Kenyan Women

Keshet Ronen  1 , Adam S Dingens  2 , Susan M Graham  3 , Walter Jaoko  4 , Kishor Mandaliya  5 , R Scott McClelland  6 , Julie Overbaugh  7
Affiliations

Comprehensive Characterization of Humoral Correlates of Human Immunodeficiency Virus 1 Superinfection Acquisition in High-risk Kenyan Women

Keshet Ronen et al. EBioMedicine. 2017 Apr.

Abstract

HIV-1 superinfection, in which an infected individual acquires a second HIV-1 infection from a different partner, is one of the only settings in which HIV acquisition occurs in the context of a pre-existing immune response to natural HIV infection. There is evidence that initial infection provides some protection from superinfection, particularly after 6months of initial infection, when development of broad immunity occurs. Comparison of the immune response of superinfected individuals at the time of superinfection acquisition to that of individuals who remain singly infected despite continued exposure can shed light on immune correlates of HIV acquisition to inform prophylactic vaccine design. We evaluated a panel of humoral immune responses in the largest published group of superinfected individuals (n=21), compared to a set of 3:1 matched singly infected controls from the same cohort. The immune functions studied included plasma neutralization, plasma and cervical antibody-dependent cellular cytotoxicity, and plasma IgG and IgA binding to a panel of 18 envelope antigens, including correlates of HIV acquisition in the RV144 vaccine trial, IgG binding to V1V2 and IgA binding to gp140. Association between each immune function and HIV superinfection was evaluated using conditional logistic regression. No significant associations were detected between any of the immune functions and superinfection acquisition. This study constitutes the most comprehensive and detailed characterization of multiple immune correlates of superinfection to date. The results suggest that immune responses not commonly measured in current HIV studies may be important in protection from HIV infection, and these or a more robust humoral response than that seen in naturally infected women may be needed for a protective vaccine.

Keywords: Antibody; Binding; HIV; Immune correlate; Neutralization; Superinfection.

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Figures

Fig. 1
Fig. 1
Neutralizing antibody breadth (a) and potency (b) in superinfection cases and controls. Colors and symbols represent superinfection cases (study identification numbers displayed) and their matched singly infected controls. Breadth and potency scores were calculated as described in the Materials and Methods. P-values are from conditional logistic regression.
Fig. 2
Fig. 2
Plasma (a) and cervical (b) antibody-dependent cellular cytotoxicity in superinfection cases and controls. Colors and symbols represent superinfection cases (study identification numbers displayed) and their matched singly infected controls. Results are normalized to a positive control (HIVIg). P-values are from conditional logistic regression.
Fig. 3
Fig. 3
Plasma binding antibody in superinfection cases and controls a. IgG binding to V1V2 scaffold proteins. b. IgA binding to gp140. Antigenic variants are named above each graph. Colors and symbols represent superinfection cases (study identification numbers displayed) and their matched singly infected controls. Results are background-subtracted and log-transformed. P-values are from conditional logistic regression.
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