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Showing modest efficacy, the RV144 HIV-1 vaccine clinical trial utilized a non-replicating canarypox viral vector and a soluble gp120 protein boost. Here we built upon the RV144 strategy by developing a novel combination of a replicating, but highly-attenuated Vaccinia virus vector, NYVAC-KC, and plant-produced HIV-1 virus-like particles (VLPs). Both components contained the full-length Gag and a membrane anchored truncated gp41 presenting the membrane proximal external region with its conserved broadly neutralizing epitopes in the pre-fusion conformation. We tested different prime/boost combinations of these components in mice and showed that the group primed with NYVAC-KC and boosted with both the viral vectors and plant-produced VLPs have the most robust Gag-specific CD8 T cell responses, at 12.7% of CD8 T cells expressing IFN-γ in response to stimulation with five Gag epitopes. The same immunization group elicited the best systemic and mucosal antibody responses to Gag and dgp41 with a bias towards IgG1. [ABSTRACT FROM AUTHOR]

Abstract: Correlation of hepatitis C virus (HCV) spontaneous resolution with Th1 and CD8+CTL responses during natural infection implies the potentiality of poly-CTL-epitopic HCV vaccines. We recently reported in silico design and construction of DNA vaccines (pcPOL-plasmids) harboring HCV CTL epitopes. Herein, we provide data of mice immunization by pcPOL, (encoding; core132–142 [C], E2405–414 [E4], E2614–622 [E6] and NS31406–1415 [N] CD8+CTL epitopes as CE4E6N polytope) and its HBsAg-fused counterpart (pcHPOL), compared to the adjuvant-formulated (Montanide+CpG) CE4E6N synthetic-peptide immunization. All vaccinated groups developed different levels of cellular responses, however, only the pcHPOL-immunized mice elicited strong CTLs and IFN-γ-secreting cells that were further augmented towards a Th1 response and partial tumor protection by DNA-prime/peptide-boosting regimen. Priming with HBsAg alone could not afford its augmenting effect indicating the importance of priming by polytope itself. Hence, fusion of immunocarriers like HBsAg conjoined with DNA-prime/peptide-boost immunization regimen seems a strategy to enhance the epitope-specific immune responses towards poly-CTL-epitopic vaccines. [Copyright &y& Elsevier]

Abstract: Previously, replicating adenovirus type 5 host range (Ad5hr)-HIV/SIV recombinant priming in combination with SIV envelope boosting, resulted in significant, durable protection in 39% of rhesus macaques after SIVmac251 challenge. Both Env-specific antibody mediating ADCC, and cellular immunity correlated with protection. Here we evaluate the relative immunogenicities of novel HIV proteins and their contribution to protection in a SHIV89.6P model. All groups were primed with Ad-HIVenv 89.6P , SIVgag 239 , and SIVnef 239 recombinants. One group was not boosted, one received HIV89.6Pgp140ΔCFI protein, and one a novel HIV-1 poly-peptide “peptomer”. The HIV89.6Pgp140ΔCFI protein in adjuvant strongly boosted Env-specific antibody and memory T cell responses in blood and tissue, resulting in significant reductions in acute and set point viremia. Macaques not boosted, showed a significant reduction in set point viremia, a full 32 weeks after the last Ad priming immunization. The HIV peptomer-boosted group showed a trend toward chronic viremia reduction, but was not protected. [Copyright &y& Elsevier]

Abstract: DNA vaccines and recombinant Listeria monocytogenes that express and secrete SIV Gag and Env antigens were combined in a nonhuman primate prime-boost immunogenicity study followed by a challenge with SIV239. We report that recombinant DNA vaccine delivered intramuscularly, and recombinant L. monocytogenes delivered orally each individually have the ability to induce CD8+ and CD4+ T cell immune responses in a nonhuman primate. Four rhesus monkeys were immunized at weeks 0, 4, 8, and 12 with the pCSIVgag and pCSIVenv DNA plasmids and boosted with SIV expressing L. monocytogenes vaccines at weeks 16, 20, and 28. Four rhesus monkeys received only the L. monocytogenes vaccines at weeks 16, 20, and 28. A final group of monkeys served as a control group. Blood samples were taken before vaccination and 2 weeks post each injection and analyzed by ELISPOT for CD4+ and CD8+ T cell responses. Moderate vaccine induced SIV-specific cellular immune responses were observed following immunization with either DNA or L. monocytogenes vectors. However, the SIV antigen-specific immune responses were significantly increased when Rhesus macaques were primed with SIV DNA vaccines and boosted with the SIV expressing L. monocytogenes vectors. In addition, the combined vaccine was able to impact SIV239 viral replication following an intrarectal challenge. This study demonstrates for the first time that oral L. monocytogenes can induce a cellular immune response in a nonhuman primate and is able to enhance the efficacy of a DNA vaccine as well as provide modest protection against SIV239 challenge. [Copyright &y& Elsevier]