BASIC SCIENCE

Viral control in chronic HIV-1 subtype C infection is associated with enrichment of p24 IgG1 with Fc effector activity

Chung, Amy W.^a,b,*; Mabuka, Jenniffer M.^c,d,*; Ndlovu, Bongiwe^d; Licht, Anna^a; Robinson, Hannah^a; Ramlakhan, Yathisha^d; Ghebremichael, Musie^a; Reddy, Tarylee^e; Goulder, Philip J.R.^f; Walker, Bruce D.^a,d; Ndung’u, Thumbi^a,c,d,g,*; Alter, Galit^a,*

Author Information

^aRagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA, USA

^bDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Australia

^cKwaZulu-Natal Research Institute for TB and HIV

^dHIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal

^eBiostatistics Unit, Medical Research Council, Durban, South Africa

^fDepartment of Paediatrics, University of Oxford, Oxford OX1 3SY, UK

^gMax Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.

Correspondence to Thumbi Ndung’u, KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), University of KwaZulu-Natal, 719 Umbilo Road, Durban 4013, South Africa. Tel: +27 31 260 4727; fax: +27 31 260 4623; e-mail: [email protected]

Received 16 October, 2017

Revised 19 January, 2018

Accepted 22 January, 2018

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com).

AIDS 32(10):p 1207-1217, June 19, 2018. | DOI: 10.1097/QAD.0000000000001812

Abstract

Objective:

Postinfection HIV viral control and immune correlates analysis of the RV144 vaccine trial indicate a potentially critical role for Fc receptor-mediated antibody functions. However, the influence of functional antibodies in clade C infection is largely unknown.

Design:

Plasma samples from 361 chronic subtype C-infected, antiretroviral therapy-naive participants were tested for their HIV-specific isotype and subclass distributions, along with their Fc receptor-mediated functional potential.

Method:

Total IgG, IgG subclasses and IgA binding to p24 clade B/C and gp120 consensus C proteins were assayed by multiplex. Antibody-dependent uptake of antigen-coated beads and Fc receptor-mediated natural killer cell degranulation were evaluated as surrogates for antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC), respectively.

Results:

p24 IgG1 was the only subclass associated with viral control (P = 0.01), with higher p24-specific ADCP and ADCC responses detected in individuals with high p24 IgG1. Although p24 IgG1 levels were enriched in patients with elevated Gag-specific T-cell responses, these levels remained an independent predictor of low-viral loads (P = 0.04) and high CD4⁺ cell counts (P = 0.004) after adjusting for Gag-specific T-cell responses and for protective HLA class I alleles.

Conclusion:

p24 IgG1 levels independently predict viral control in HIV-1 clade C infection. Whether these responses contribute to direct antiviral control via the recruited killing of infected cells via the innate immune system or simply mark a qualitatively superior immune response to HIV, is uncertain, but highlights the role of p24-specific antibodies in control of clade C HIV-1 infection.

Article Keywords

Keywords
antibody, antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, chronic, Gag, HIV-1 subtype C, natural killer cell degranulation, p24

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Viral control in chronic HIV-1 subtype C infection is associated with enrichment of p24 IgG1 with Fc effector activity