Efficient expansion of HIV-1-specific T cell responses by homologous immunization with recombinant Semliki Forest virus particles

Abstract

Vaccines based on recombinant viruses represent a promising strategy for the development of a prophylactic vaccine against HIV-1. However, despite a proven capacity to stimulate potent HIV-1-specific immune responses, viral systems have limited utility in homologous prime-boost regimens due to the generation of anti-vector immune responses. It is therefore important to develop a diverse set of vaccine candidates that can be combined in different heterologous prime-boost regimens and/or to identify a vaccine candidate that is less sensitive to anti-vector mediated immunity. In this report, we describe the design and pre-clinical immunogenicity of a Semliki Forest virus-based vaccine, VREP-C, encoding Indian origin HIV-1 clade C antigens. We show that a single immunization with VREP-C stimulates HIV-1-specific IFNgamma ELISPOT responses, which were efficiently boosted by a second and a third homologous VREP-C immunization resulting in highly potent cytotoxic T cell responses. These results suggest that VREP-C may be a valuable component of a future prophylactic vaccine against HIV-1.

Viral vector-based prime-boost immunization regimens: a possible involvement of T-cell competition

“…To achieve optimal responses and specifically to induce strong memory CTL responses, at least two immunizations with rSFV are required. [15][16][17] Within a few hours after infection with rSFV, target cells express the viral nonstructural proteins that make up the replicase complex, and start to produce large amounts of recombinant protein. Infected cells subsequently die through apoptosis and peptides derived from the recombinant protein may then be presented by professional antigen-presenting cells (APC) in the context of major histocompatibility complex (MHC) class I and class II molecules in a process of cross-presentation.…”

“…15,16,[18][19][20][21][22][23][24] The strong booster effect of a second or third immunization with rSFV in a homologous prime-boost protocol is remarkable, as immunization with rSFV has been found to induce robust SFV-specific antibody responses. 15,17 In this study, we have investigated the effect of vector-specific immunity, induced by a priming immunization with rSFV, on transgene expression and CTL activation by a subsequent injection of SFV expressing the E6 and E7 antigens from human papillomavirus (HPV) (SFVeE6,7). We furthermore determined which immune mechanisms may be involved in SFV vector-specific immunity by administration of rSFV to mice with passively transferred SFV-specific antibodies or mice pre-immunized with an irrelevant rSFV vector.…”

Comparative Prime-Boost Vaccinations Using Semliki Forest Virus, Adenovirus, and ALVAC Vectors Demonstrate Differences in the Generation of a Protective Central Memory CTL Response against the P815 Tumor

“…Recombinant adenovirus, ALVAC, and Semliki Forest virus (SFV) have been tested in several preclinical studies (10,(37)(38)(39)(40)(41)(42)(43). It has been shown previously that SFV viral particles can be used for multiple immunizations without hampering the additive effect on the immune response, making the SFV viral vector an attractive vector (38,42).…”

“…It has been shown previously that SFV viral particles can be used for multiple immunizations without hampering the additive effect on the immune response, making the SFV viral vector an attractive vector (38,42). Adeno-and SFV viral particles expressing the P1A Ag have been shown previously to induce P1A-specific cytotoxic T cell responses in blood (12) and in spleen (44,45).…”

HIV-189.6 Gag expressed from a replication competent HSV-1 vector elicits persistent cellular immune responses in mice

“…Some of these candidates have not yet been tested in humans but are non-toxic and elicit significant CMI responses in animal models. These include alphaviruses [55][56][57], polioviruses [58], and rhabdoviruses [52]. Candidate vaccine vectors in more advanced stages of development are under evaluation in human clinical trials.…”