Increased frequencies of CD8+CD57+ T cells are associated with antibody neutralization breadth against HIV in viraemic controllers.

Christine D Palmer,Filippos Porichis,Stephanie Jost,Marisol Romero‐Tejeda,Ainsley Lockhart,Ariel Goldenthal,Michael S Seaman,Bruce D Walker,Alicja Piechocka‐Trocha,Eileen P Scully,Lori B Chibnik

doi:10.7448/ias.19.1.21136

Abstract

IntroductionAn effective prophylactic vaccine against HIV will need to elicit antibody responses capable of recognizing and neutralizing rapidly evolving antigenic regions. The immunologic milieu associated with development of neutralizing antibody breadth remains to be fully defined. In this study, we sought to identify immunological signatures associated with neutralization breadth in HIV controllers. We applied an immune monitoring approach to analyze markers of T cell and myeloid cell activation by flow cytometry, comparing broad neutralizers with low- and non-neutralizers using multivariate and univariate analyses.MethodsAntibody neutralization breadth was determined, and cryopreserved peripheral blood mononuclear cells were stained for T cell and myeloid cell activation markers. Subjects were grouped according to neutralization breadth, and T cell and myeloid cell activation was analyzed by partial least squares discriminant analysis to determine immune signatures associated with high neutralization breadth.ResultsWe show that neutralization breadth in HIV viraemic controllers (VC) was strongly associated with increased frequencies of CD8+CD57+ T cells and that this association was independent of viral load, CD4 count and time since HIV diagnosis.ConclusionsOur data show elevated frequencies of CD8+CD57+ T cells in VC who develop neutralization breadth against HIV. This immune signature could serve as a potential biomarker of neutralization breadth and should be further investigated in other HIV-positive cohorts and in HIV vaccine trials.

Highlights

An effective prophylactic vaccine against HIV will need to elicit antibody responses capable of recognizing and neutralizing rapidly evolving antigenic regions
Determination of neutralizing antibody breadth and immune monitoring for markers of T cell and myeloid cell activation was performed on all samples
We investigated the relationship of immune signatures identified through routinely used immune monitoring panels with production of neutralizing antibody breadth in a cohort of HIV viraemic controllers (VC)

Summary

Introduction

An effective prophylactic vaccine against HIV will need to elicit antibody responses capable of recognizing and neutralizing rapidly evolving antigenic regions. HIV infection leads to the generation of HIV-specific antibodies, in particular against components of the HIV envelope (Env), these antibodies are largely non-neutralizing, appear to have little effect on viral load (VL), and any strain-specific neutralizing effects that do develop are likely to contribute to viral evolution and escape (reviewed in [1,6]). Isolation and characterization of such broadly neutralizing antibodies (bNAbs) revealed that these antibodies are highly somatically mutated [10] and carry insertions, deletions or long complementary determining regions [10Á12] that make it difficult to elicit such antibodies via conventional immunization strategies [13] While development of such bNAbs in the setting of chronic infection does not necessarily confer clinical benefit to the individual in whom they are induced, a vaccine that elicits this type of breadth should have substantial protective efficacy for uninfected persons

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Results

Conclusion