Elsevier

EBioMedicine

Volume 18, April 2017, Pages 216-224
EBioMedicine

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

https://doi.org/10.1016/j.ebiom.2017.04.005Get rights and content
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open access

Highlights

  • We conducted a case-control study of the association between humoral immune functions and HIV superinfection (SI).

  • Neutralization, antibody-dependent cellular cytotoxicity, and IgG and IgA binding to Env antigens were interrogated.

  • We found no significant associations between SI acquisition and neutralizing or non-neutralizing antibody activity.

HIV superinfection (repeat infection from a second partner) is a unique situation in which infection occurs in the presence of a pre-existing HIV-specific immune response. Identification of immune deficits in superinfected individuals prior to superinfection can shed light on immune functions associated with HIV acquisition, and help inform prophylactic vaccine development. We compared various antibody measures in superinfected women vs. women who remained singly infected. We found no evidence that deficits in any of the measures analyzed were associated with superinfection risk. This suggests a prophylactic vaccine may need to elicit stronger or different immune responses than those investigated here.

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 6 months 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

HIV
Superinfection
Antibody
Neutralization
Binding
Immune correlate

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Equal contribution.