Induction of circulating T follicular helper cells and regulatory T cells correlating with HIV-1 gp120 variable loop antibodies by a subtype C prophylactic vaccine tested in a Phase I trial in India

Sivasankaran Munusamy Ponnan; Soumya Swaminathan; Kannan Tiruvengadam; Vidyavijayan K K; Narayana Cheedarla; Manohar Nesakumar; Sujitha Kathirvel; Rajat Goyal; Nikhil Singla; Joyeeta Mukherjee; Philip Bergin; Jakub T Kopycinski; Jill Gilmour; Srikanth Prasad Tripathy; Hanna Elizabeth Luke

doi:10.1371/journal.pone.0203037

Induction of circulating T follicular helper cells and regulatory T cells correlating with HIV-1 gp120 variable loop antibodies by a subtype C prophylactic vaccine tested in a Phase I trial in India

PLoS One. 2018 Aug 29;13(8):e0203037. doi: 10.1371/journal.pone.0203037. eCollection 2018.

Authors

Affiliations

¹ National Institute for Research in Tuberculosis (Indian Council of Medical Research), Chennai, India.
² International AIDS Vaccine Initiative, New Delhi, India.
³ IAVI Human Immunology Laboratory, Imperial College, London, United Kingdom.

Abstract

A Phase I HIV-1 vaccine trial sponsored by the International AIDS Vaccine Initiative (IAVI) was conducted in India in 2009 to test a subtype C prophylactic vaccine in a prime-boost regimen comprising of a DNA prime (ADVAX) and MVA (TBC-M4) boost. The trial demonstrated that the regimen was safe and well tolerated and resulted in enhancement of HIV-specific immune responses. Preliminary observations on vaccine-induced immune responses were limited to analysis of neutralizing antibodies and IFN-γ ELISPOT response. The present study involves a more detailed analysis of the nature of the vaccine-induced humoral immune response using specimens that were archived from the volunteers at the time of the trial. Interestingly, we found vaccine induced production of V1/V2 and V3 region-specific antibodies in a significant proportion of vaccinees. Variable region antibody levels correlated directly with the frequency of circulating T follicular helper cells (Tfh) and regulatory T cells (Treg). Our findings provide encouraging evidence to demonstrate the immunogenicity of the tested vaccine. Better insights into vaccine-induced immune responses can aid in informing future design of a successfulHIV-1 vaccine.

Publication types

Clinical Trial, Phase I
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

AIDS Vaccines / immunology*
B-Lymphocytes / immunology
Female
HIV Antibodies / blood*
HIV Envelope Protein gp120 / immunology*
HIV-1
Humans
Immunity, Humoral
India
Male
Peptide Fragments / immunology
T-Lymphocytes, Helper-Inducer / immunology*
T-Lymphocytes, Regulatory / immunology*
Vaccination

Substances

AIDS Vaccines
HIV Antibodies
HIV Envelope Protein gp120
HIV envelope protein gp120 (135-148)
HIV envelope protein gp120 (305-321)
Peptide Fragments
gp120 protein, Human immunodeficiency virus 1

Grants and funding

The vaccine trial and the present study were supported and coordinated by the International AIDS Vaccine Initiative (IAVI). IAVI’s work is made possible by generous support from many donors including the Bill & Melinda Gates Foundation, the Ministry of Foreign Affairs of Denmark, Irish Aid, the Ministry of Finance of Japan in partnership with The World Bank, the Ministry of Foreign Affairs of the Netherlands, the Norwegian Agency for Development Cooperation (NORAD), the United Kingdom Department for International Development (DFID), and the USAID. The full list of IAVI donors is available at www.iavi.org. This study was made possible by the generous support of the American people through funding from United States Agency for International Development (USAID; Grant ID: 2233). The content is the responsibility of the authors and does not necessarily reflect the views of USAID or the United States Government.