Robust Recall and Long-Term Memory T-Cell Responses Induced by Prime-Boost Regimens with Heterologous Live Viral Vectors Expressing Human Immunodeficiency Virus Type 1 Gag and Env Proteins

Abstract

We investigated long-term memory and recall cellular immune responses to human immunodeficiency virus type 1 (HIV-1) Env and Gag proteins elicited by recombinant vesicular stomatitis viruses (VSVs) expressing Env and Gag. More than 7 months after a single vaccination with VSV-Env, ϳ6% of CD8 ؉ splenocytes stained with major histocompatibility complex class I tetramers containing the Env p18-I10 immunodominant peptide and showed a memory phenotype (CD44 Hi ). The level of tetramer-positive cells in memory was about 14% of the peak primary response. Recall responses elicited in these mice 5 days after boosting with a heterologous recombinant vaccinia virus expressing HIV-1 Env showed that 40 to 45% of CD8 ؉ splenocytes were tetramer positive and activated (CD62L Lo ), and these cells produced gamma interferon after stimulation with Env peptide, indicating that they were functional. Five months after the boost, the long-term memory cell population (tetramer positive, CD44 Hi ) constituted 30% of the CD8 ؉ splenocytes. Recall responses to HIV-1 Gag were examined in mice primed with VSV recombinants expressing HIV-1 Gag protein and boosted with a vaccinia virus recombinant expressing Gag. Using this protocol, we found that ϳ40% of CD8 ؉ splenocytes were activated (CD62L Lo ) and specific for a Gag immunodominant peptide (tetramer positive). The high-level Gag recall response elicited by the vaccinia virus-Gag was greater than that obtained by boosting with a VSV-Gag vector with a different VSV glycoprotein. The corresponding levels of CD44 Hi memory cells were also higher long after boosting with vaccinia virus-Gag than after boosting with a glycoprotein exchange VSV-Gag. Our results show that VSV vectors elicit high-level memory CTL responses and that these can be amplified as much as six-to sevenfold using a heterologous boosting vector.

Highly Effective Control of an AIDS Virus Challenge in Macaques by Using Vesicular Stomatitis Virus and Modified Vaccinia Virus Ankara Vaccine Vectors in a Single-Boost Protocol

“…In inbred mice, priming with VSV Gag and boosting with vaccinia virus Gag generated about five times more recall and long-term CD8 ϩ T cells than a VSV Gag prime and VSV Gag (G-exchange) boost (11). In macaques a clear trend in the same direction is evident, but the differences in the immune responses do not reach statistical significance.…”

“…These studies showed that mice immunized with an rVSV expressing HIV-1 Gag and boosted with a completely heterologous vaccinia virus recombinant expressing HIV-1 Gag generated a fivefold increase in peak Gag-specific CD8 ϩ T cells relative to the levels seen in mice immunized with a VSV vector and boosted with a VSV G protein exchange vector expressing Gag (11). The population of Gag-specific T cells persisting long term was also increased fivefold by the heterologous vaccinia boost.…”

The Shiga toxin B‐subunit targets antigen in vivo to dendritic cells and elicits anti‐tumor immunity

“…We found that vaccination with STxB-OVA induced OVA-specific CD8 + T cells detected ex vivo without the need for in vitro restimulation, and this response was long-lasting, as it was still observed at least 3 months after immunization. Such robust and long-lasting memory CD8 + T cell responses have been observed with recombinant viruses [57,58] and ex vivo DC pulsed with antigens [59,60] but with very few carrier proteins [61,62].…”

Naloxone/alum mixture a potent adjuvant for HIV-1 vaccine: induction of cellular and poly-isotypic humoral immune responses

“…infection. 23,25 In this study, the results of CTL activity demonstrated that immunization with vaccine in combination with NLX and alum mixture did not show any significant difference vs. the alum adjuvanted group. However, the study of Molla Hassan et al showed that NLX significantly increased CTL activity for a cancer vaccine in comparison to the un-adjuvanted vaccine.…”