Virus-like particles as HIV-1 vaccines

Abstract

Traditional successful antiviral vaccines have relied mostly on live-attenuated viruses. Live-attenuated HIV vaccine candidates are not ideal as they pose risks of reversion, recombination or mutations. Other current HIV vaccine candidates have difficulties generating broadly effective neutralising antibodies and cytotoxic T cell immune responses to primary HIV isolates. Virus-like-particles (VLPs) have been demonstrated to be safe to administer to animals and human patients as well as being potent and efficient stimulators of cellular and humoral immune responses. Therefore, VLPs are being considered as possible HIV vaccines. Chimeric HIV-1 VLPs constructed with either HIV or SIV capsid protein plus HIV immune epitopes and immuno-stimulatory molecules have further improved on early VLP designs, leading to enhanced immune stimulation. The administration of VLP vaccines via mucosal surfaces has also emerged as a promising strategy with which to elicit mucosal and systemic humoral and cellular immune responses. Additionally, new information on antigen processing and the presentation of particulate antigens by dendritic cells (DCs) has created new strategies for improved VLP vaccine candidates. This paper reviews the field of HIV-1 VLP vaccine development, focusing on recent studies that will likely uncover promising prospects for new HIV vaccines.

Incorporation of High Levels of Chimeric Human Immunodeficiency Virus Envelope Glycoproteins into Virus-Like Particles

“…Recent reports indicate that HIV Env-containing VLPs elicit both arms of immunity and induce specific immune responses at local and distal mucosal surfaces (4,11,12,33). To elicit antibodies with broad neutralization capacity for genetically diverse HIV-1 isolates, it is important to design antigens in which the conserved neutralizing epitopes are exposed.…”

“Wrapped Up” Vaccines in the Context of HIV-1 Immunotherapy

“…Such vaccines would elicit or boost HIV specific cytotoxic T cells (CTLs) to eliminate infected cells and CD4 + T cells, which can help to induce and maintain B cell and CD8 + T cells responses [92]. Several strategies are currently under investigation to establish effective T cell responses in either a preventive or therapeutic setting either based on protein [93,94] or peptide [95] vaccinations, virus like particles (VPLs) [96], DNA vaccination using viral vectors [97,98], prime-boost vaccinations [99,100] or DC-based vaccines [101][102][103][104][105][106][107][108][109].…”

“…These pseudo-virions are produced in baculovirus or vaccinia virus expression systems where Gag and Env proteins from HIV or SIV are co-expressed and spontaneously assembled. The immunogenicity of these vaccines was only modest in non-human primates [96], however, efficiency was greatly improved when combined with a HIV DNA vaccine prime [138].…”

HIV-1 subtype C Pr55gag virus-like particle vaccine efficiently boosts baboons primed with a matched DNA vaccine

“…In addition, HIV-1 Pr55 gag VLPs are safe, easy to produce and have the potential of including chimaeric antigens (Doan et al, 2005). Their particulate nature and size, which approximates that of HIV-1, make them more likely to stimulate the immune system better than non-particulate antigens.…”