Humoral responses to HIVconsv induced by heterologous vaccine modalities in rhesus macaques

Immunity, Inflammation and Disease

Nicola J. Borthwick¹  Maximillian Rosario²  Torben Schiffner³  Emma Bowles²  Tina Ahmed¹  Peter Liljeström⁵  Guillaume E. Stewart-Jones²  Jan W. Drijfhout⁴  Cornelis J. M. Melief⁴ 

[1] Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, UK;Nuffield Department of Medicine, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford, UK;Nuffield Department of Medicine, The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, UK;Departement of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, the Netherlands;Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

关键词: Antibodies;    conserved regions;    HIV vaccines;    macaques;    synthetic long peptides;   

DOI  :  10.1002/iid3.52

来源: Wiley

【 摘 要 】

Abstract

Vaccines delivering T cell immunogen HIVconsv vectored by plasmid DNA, non-replicating simian adenovirus and non-replicating modified vaccinia virus Ankara (MVA) are under clinical evaluation in phase I/IIa trials in UK, Europe, and Africa. While these vaccines aim to induce effector T cell responses specific for HIV-1, we here characterized the humoral responses induced by HIVconsv administration to macaques using six different vaccine modalities: plasmid DNA, human adenovirus serotype 5, simian adenovirus serotype 63, MVA, Semliki Forest virus replicons, and adjuvanted overlapping synthetic long peptides (SLP). We found that only the SLP formulation, but none of the genetic vaccine platforms induced antibodies recognizing linear HIVconsv epitopes, median 32/46 SLP.HIVconsv peptides. These antibodies bound to 15-mer and SLP peptides, recombinant gp120 and trimeric gp140 of HIV-1 Bal, YU2, JRFL, and UG037, but failed to react with HIV-1 Bal and IIIB virions and HIV-1 Bal- and IIIB-infected human cells, and consequently failed to induce neutralizing antibodies. The HIVconsv immunogen contains conserved regions derived from Gag, Pol, Vif, and Env proteins of HIV-1, and antibodies induced by the SLP.HIVconsv vaccination resulted in positive signals in routine HIV-1 tests. Thus, only HIVconsv delivered by SLP resulted in seroconversion, an observation that provides important guidance for recruiting volunteers into future clinical trials. Furthermore, our data confirms that vaccine delivery by SLP induces humoral as well as cellular immune responses and could be considered for inclusion in future vaccine regimens where this is required.

【 授权许可】

CC BY   
© 2015 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.