Safety and Immunogenicity of Recombinant Human Immunodeficiency Virus-Like Particles in Rodents and Rhesus Macaques

Abstract

Data from long-term non-progressing human immunodeficiency virus (HIV)- infected individuals and populations at high risk suggest that an early cytolytic T cell response rather than the humoral immune response might be involved in controlling disease progression. These observations may be used as a guide to the type of response that a vaccine should induce. To clarify the role of different arms of the immune system in conferring protection, the candidate vaccine should allow a regulated, selective induction of different immune responses. Based on a better understanding of the molecular mechanisms regulating the morphogenesis of HIV, we developed an autologous, non-replicating and safe antigen delivery system. This system takes advantage of molecular characteristics of the HIV group-specific antigens (gag) to self-assemble to highly immunogenic virus-like particles (VLP). The immunogenicity of the gag-derived VLP was expanded either by replacing defined domains by selected HIV-1 cytotoxic T lymphocyte (CTL) epitopes (type 1 VLP) or by stable anchoring derivatives of the HIV-1 envelope protein on the surface of the VLP (type 2 VLP). In complete absence of adjuvants, type 1 and type 2 VLP stimulated CD8+ CTL in BALB/c mice, which specifically recognised HIV sequences. In contrast to type 1 VLP, generating an HIV-specific CTL response in the absence of e«v-specific antibodies, type 2 VLP induced both arms of the immune system including reasonable levels of neutralising antibodies. Initial studies performed in rhesus macaques confirmed these results. Thus, depending on the type and formulation of the VLP, the proposed antigen delivery system allows either the induction of a CTL response (1) in the absence and (2) the presence of an envelope-specific antibody response. A comparison of these approaches in appropriate animal models might contribute to further define the correlates of protection.

Systemic, Mucosal, and Heterotypic Immune Induction in Mice Inoculated with Venezuelan Equine Encephalitis Replicons Expressing Norwalk Virus-Like Particles

“…VLPs are currently being examined for vaccine purposes for a number of other human pathogens, including rotavirus, papillomavirus, polyomavirus, and human immunodeficiency virus (HIV) (12,23,60,67). A variety of vectors have been used to express VLPs, including vaccinia viruses, baculoviruses, alphaviruses, yeasts, and bacteria, among others (6,49,59).…”

Characterization of a Virtually Full-Length Human Immunodeficiency Virus Type 1 Genome of a Prevalent Intersubtype (C/B′) Recombinant Strain in China

“…11:184, 1990). With time a shift occurred toward B-Thai (BЈ) genotypes, and the former predominant prototype B has now been taken over by B-Thai variants (15,36). The second epidemic was imported to the same area in the early 1990s, most probably by Indian IDUs carrying subtype C strains (30; C. C. Luo, C. Tian, D. J. Hu, M. Kai, T. Dondero, and X. Zhang, Letter, Lancet 345:1051-1052, 1995).…”

Virus‑like particles as a vaccine delivery system: Myths and facts

“…Although none of the retrovirus derived VLPs are yet at the stage that they are being used in clinical vaccine trials, initial experiments in animal models are promising. 57,58 VLPs for SARS Coronavirus as a basis for vaccination were produced rapidly following the SARS outbreak in 2002-2003. 54,55 However the control of SARS Coronavirus by epidemiological measures, continued lack of re-emergence of the virus, and difficulties working directly with the virus have severely limited the development of SARS VLPs as vaccine.…”