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

Nicola J Borthwick,Jan W Drijfhout,Torben Schiffner,Peter Liljeström,Tomáš Hanke,Guillaume E Stewart‐Jones,Maximillian Rosario,Tina Ahmed,Emma Bowles,Cornelis J M Melief

doi:10.1002/iid3.52

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.

Highlights

Even against the background of antiretroviral treatment and prevention, a vaccine against HIV-1 infection will always be a key to controlling the AIDS epidemic
To induce sufficiently robust responses to the transgene product and avoid the build-up of anti-vector antibodies, which stands the risk of decreasing vaccine take [8, 9], the HIV-1 subunits are typically delivered by a sequential combination of heterologous vectors in prime-boost regimens [5]
The HIVconsv immunogen was designed to contain only those regions of HIV-1 that are conserved across the major clades

Summary

Introduction

Even against the background of antiretroviral treatment and prevention, a vaccine against HIV-1 infection will always be a key to controlling the AIDS epidemic Such a vaccine will induce balanced responses mediated by effective killer T cells and beneficial antibodies. The specificity of vaccine-elicited responses is dictated by the HIV-1-derived immunogens, while the magnitude, longevity, functionality, and anatomical distribution of the individual components of immune responses are primarily determined by the route and means of the delivery of the. To induce sufficiently robust responses to the transgene product and avoid the build-up of anti-vector antibodies, which stands the risk of decreasing vaccine take [8, 9], the HIV-1 subunits are typically delivered by a sequential combination of heterologous vectors in prime-boost regimens [5]

Methods

Results

Conclusion