Format

Send to

Choose Destination
AIDS. 2018 Jun 19;32(10):1207-1217. doi: 10.1097/QAD.0000000000001812.

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

Author information

1
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA, USA.
2
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Australia.
3
KwaZulu-Natal Research Institute for TB and HIV.
4
HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal.
5
Biostatistics Unit, Medical Research Council, Durban, South Africa.
6
Department of Paediatrics, University of Oxford, Oxford OX1 3SY, UK.
7
Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.

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.

PMID:
29620716
PMCID:
PMC5980776
[Available on 2019-06-19]
DOI:
10.1097/QAD.0000000000001812

Supplemental Content

Full text links

Icon for Wolters Kluwer
Loading ...
Support Center