Highly efficient neutralization by plasma antibodies from human immunodeficiency virus type-1 infected individuals on antiretroviral drug therapy

Raiees Andrabi, M. A. Makhdoomi, Rajesh Kumar, Manju Bala, Hilal Parray, Arjun Gupta, Ankita Kotnala, Velpandian Thirumurthy, Kalpana Luthra

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Little is known about the neutralizing antibodies induced in HIV-1 patients on antiretroviral treatment, which constitute an interesting group of individuals with improved B cell profile. Plasma samples from 34 HIV-1 seropositive antiretroviral drug treated (ART) patients were tested for neutralization against a panel of 14 subtype-A, B and C tier 1 and tier 2 viruses in TZM-bl assay. Of the 34 plasma samples, remarkably all the plasma samples were able to neutralize at least one virus while 32 (94 %) were found to neutralize ≥50 % viruses tested. In terms of overall neutralization frequency, approximately 86 %, 68 % and 17 % of the virus/plasma combinations showed 50 % neutralizing activity at 1>60, 1≥200 and 1≥2000 dilutions respectively. The improvement in neutralizing activity was shown to be associated with ART in two follow up patients. The neutralization of viruses by two representative plasma samples, AIIMS221 and AIIMS265, was exclusively mediated by immunoglobulin G fractions independent of ART drugs and IgG retained cross-reactive binding to recombinant gp120 proteins. We observed a positive trend of neutralization with duration of ART (p=0.06), however no such correlation was found with clinical and immunological variables like CD4 count (p=0.35), viral load (p=0.09) and plasma total IgG (p=0.46). Our study suggests that the plasma antibodies from ART patients display high neutralizing activity most likely due to an improved B cell function induced by ART despite low antigenic stimulation.

Original languageEnglish (US)
Pages (from-to)504-513
Number of pages10
JournalJournal of Clinical Immunology
Volume34
Issue number4
DOIs
StatePublished - May 2014
Externally publishedYes

Bibliographical note

Funding Information:
Acknowledgments We profoundly thank all the study participants. We acknowledge Prof. Miroslaw K. Gorny and Prof. Susan Zolla Pazner for constant technical advice and support and also for providing control antibodies. We thank DBT (BT/PR 10511/MED/29/66/2008) and ICMR (61/7/2008-BMS) for funding this work. The Fogarty AIDS International Training & Research Program (AITRP) fellowship (USA), JRF/SRF fellowship provided by Indian Council of Medical Research (ICMR) to Raiees Andrabi is acknowledged.

Keywords

  • HIV-1
  • antiretroviral therapy
  • neutralizing antibodies

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