HIV-1 sub-type C chimaeric VLPs boost cellular immune responses in mice

Sirika Pillay,Enid G Shephard,Ann E Meyers,Edward P Rybicki,Anna-Lise Williamson

doi:10.1186/1476-8518-8-7

Abstract

Several approaches have been explored to eradicate HIV; however, a multigene vaccine appears to be the best option, given their proven potential to elicit broad, effective responses in animal models. The Pr55Gag protein is an excellent vaccine candidate in its own right, given that it can assemble into large, enveloped, virus-like particles (VLPs) which are highly immunogenic, and can moreover be used as a scaffold for the presentation of other large non-structural HIV antigens. In this study, we evaluated the potential of two novel chimaeric HIV-1 Pr55Gag-based VLP constructs - C-terminal fusions with reverse transcriptase and a Tat::Nef fusion protein, designated GagRT and GagTN respectively - to enhance a cellular response in mice when used as boost components in two types of heterologous prime-boost vaccine strategies. A vaccine regimen consisting of a DNA prime and chimaeric HIV-1 VLP boosts in mice induced strong, broad cellular immune responses at an optimum dose of 100 ng VLPs. The enhanced cellular responses induced by the DNA prime-VLP boost were two- to three-fold greater than two DNA vaccinations. Moreover, a mixture of GagRT and GagTN VLPs also boosted antigen-specific CD8+ and CD4+ T-cell responses, while VLP vaccinations only induced predominantly robust Gag CD4+ T-cell responses. The results demonstrate the promising potential of these chimaeric VLPs as vaccine candidates against HIV-1.

Highlights

Several approaches have been explored to eradicate HIV; a multigene vaccine appears to be the best option, given their proven potential to elicit broad, effective responses in animal models
The importance of a cellular immune response against HIV-1 has been highlighted in several animal vaccine trials [1,2], with an abundance of evidence suggesting that an effective cellular immune response against HIV1 is able to control and suppress viraemia during primary and chronic HIV infections, and to provide longlasting protection [3,4,5]
Heterologous prime-boost vaccination has recently emerged as an effective means of enhancing T-cell responses [6,7,8], and current research suggests that HIV virus-like particles (VLPs) elicit a superior cellular immune response against HIV in animal models when used as a boost component in a prime-boost strategy [5,6]

Summary

Introduction

Several approaches have been explored to eradicate HIV; a multigene vaccine appears to be the best option, given their proven potential to elicit broad, effective responses in animal models. Previous studies have indicated the importance of including more than one HIV-1 proteins in a vaccine, due to the potential to induce broader and possibly more effective immune responses against HIV [9,10,11]. VLPs, and significantly enhanced T-cell responses elicited by a DNA vaccine to HIV-1 Gag and RT.

Results

Conclusion