Efficacy of DNA and Fowlpox Virus Priming/Boosting Vaccines for Simian/Human Immunodeficiency Virus

Abstract

Further advances are required in understanding protection from AIDS by T-cell immunity. We analyzed a set of multigenic simian/human immunodeficiency virus (SHIV) DNA and fowlpox virus priming and boosting vaccines for immunogenicity and protective efficacy in outbred pigtail macaques. The number of vaccinations required, the effect of DNA vaccination alone, and the effect of cytokine (gamma interferon) coexpression by the fowlpox virus boost was also studied. A coordinated induction of high levels of broadly reactive CD4 and CD8 T-cell immune responses was induced by sequential DNA and fowlpox virus vaccination. The immunogenicity of regimens utilizing fowlpox virus coexpressing gamma interferon, a single DNA priming vaccination, or DNA vaccines alone was inferior. Significant control of a virulent SHIV challenge was observed despite a loss of SHIV-specific proliferating T cells. The outcome of challenge with virulent SHIV mn229 correlated with vaccine immunogenicity except that DNA vaccination alone primed for protection almost as effectively as the DNA/ fowlpox virus regimen despite negligible immunogenicity by standard assays. These studies suggest that priming of immunity with DNA and fowlpox virus vaccines could delay AIDS in humans.

Immune-response profiles induced by human immunodeficiency virus type 1 vaccine DNA, protein or mixed-modality immunization: increased protection from pathogenic simian–human immunodeficiency virus viraemia with protein/DNA combination

“…These results suggest an important role for Nef and Gag cellular immune responses that appear to be driven by virus replication in the early phase of the infection. Similar results have been reported for anamnestic responses against Gag (Dale et al, 2004;Hel et al, 2006). However, for SIV Gag, pre-challenge, vaccineinduced responses were also found to correlate with suppression of virus replication when a DNA prime/ Nef-, SIV mac Nef-and SIV mac Gag-stimulated wells, per million PBMCs measured either 6 weeks after the fourth (last) immunization or 2 weeks after challenge, as well as the individual SIV Nef-and SIV Gag-specific IFN-c ELISpot responses measured 2 weeks after challenge, are plotted against the steadystate plasma virus load, measured 28 weeks after challenge.…”

Comparative Efficacy of Subtype AE Simian-Human Immunodeficiency Virus Priming and Boosting Vaccines in Pigtail Macaques

“…Second, the B subtype SHIV vaccination may have primed a broader response than the subtype AE SHIV vaccination, as discussed above. Third, partial earlier control of the B subtype SHIV challenge virus resulting in less-profound CD4 T-cell depletion may have facilitated a broader recognition of nonvaccine SHIV antigens, although we previously showed this was not related to early neutralizing antibody responses (9). The subtype AE SHIV-vaccinated animals were remarkable for their very poor recognition of non-Gag antigens (Fig.…”

“…To both assist evaluating the efficacy of subtype AE regimens suitable for use in Southeast Asia and assess protection across diverse subtypes, we studied four separate subtype AE SHIV vaccine regimens in groups of six macaques (Table 1). We included arms with (i) higher doses on the FPV boost vaccination (based on earlier work with FPV doses in macaques (12), (ii) DNA vaccination only (based on surprisingly good efficacy despite limited immunogenicity with this arm in the previous subtype-B SHIV trial [9]), and (iii) VV prime/FPV boost (based on our own and previous reports demonstrating strong T-cell immunogenicity with this approach [4,23]). The vaccine regimens are shown in Table 1.…”

“…However, the relative efficacy of SHIV vaccination with one subtype and protection against another subtype has not previously been studied. We recently performed and reported a separate B subtype SHIV DNA prime/fowlpox virus boost vaccine study using the same B subtype SHIV mn229 intrarectal challenge stock as used in this AE subtype SHIV study (9). Two of the vaccine groups in both studies received identical vaccine regimens (the DNA/FPV low-dose and three-DNA groups).…”

“…The circulating recombinant subtype AE is common in many Southeast Asian countries, including Thailand, although no preclinical efficacy studies or clinical trials with subtype AE vaccines have been reported. We previously demonstrated the safety and immunogenicity of subtype AE HIV-1 DNA and FPV vaccines in macaques (12), modeled on our previous macaque and human work with subtype B HIV-1 and SHIV vaccines (8,9,(18)(19)(20). In this study we analyzed a set of subtype AE SHIV vaccines expressing SIV Gag and Pol and HIV-1 subtype AE Env, Tat, and Rev for immunogenicity and efficacy in pigtail macaques.…”