DNA/NYVAC Vaccine Regimen Induces HIV-Specific CD4 and CD8 T-Cell Responses in Intestinal Mucosa

Abstract

In the present study, we have investigated the anatomic distribution in blood and gut mucosal tissues of memory poxvirus-specific CD4 and CD8 T cells in subjects vaccinated with smallpox and compared it with vector (NYVAC)-specific and HIV insert-specific T-cell responses induced by an experimental DNA-C/ NYVAC-C vaccine regimen. Smallpox-specific CD4 T-cell responses were present in the blood of 52% of the subjects studied, while smallpox-specific CD8 T cells were rarely detected (12%). With one exception, smallpoxspecific T cells were not measurable in gut tissues. Interestingly, NYVAC vector-specific and HIV-specific CD4 and CD8 T-cell responses were detected in almost 100% of the subjects immunized with DNA-C/NYVAC-C in blood and gut tissues. The large majority (83%) of NYVAC-specific CD4 T cells expressed ␣4␤7 integrins and the HIV coreceptor CCR5. These results demonstrate that the experimental DNA-C/NYVAC-C HIV vaccine regimen induces the homing of potentially protective HIV-specific CD4 and CD8 T cells in the gut, the port of entry of HIV and one of the major sites for HIV spreading and the depletion of CD4 T cells.

Head-to-Head Comparison of Poxvirus NYVAC and ALVAC Vectors Expressing Identical HIV-1 Clade C Immunogens in Prime-Boost Combination with Env Protein in Nonhuman Primates

“…In particular, recombinant NYVAC vectors expressing HIV-1 Env, Gag, Pol, and Nef antigens from clade B or C elicited strong, broad, and polyfunctional T-cell immune responses in mice, nonhuman primates, and humans, together with varied levels of humoral re-sponses against HIV-1 gp120 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)). An additional feature is that the current NYVAC vectors preferentially trigger CD4 ϩ T-cell responses (13,14,24,25) in both humans and macaques, inferring immunologically the recruitment of stronger B-cell responses than ALVAC-based vectors.…”

Safety and Immunogenicity of DNA Prime and Modified Vaccinia Ankara Virus-HIV Subtype C Vaccine Boost in Healthy Adults

“…Anti-MVA responses do not appear to significantly impair subsequent immune responses, though immune responses tend to plateau after two immunizations (12,14,16,17). To circumvent antivector immunity and prime immune responses, the use of DNA as prime in "prime-boost" regimens with MVA, adenovirus, and other vector-based vaccines as the boost has become a common strategy (18)(19)(20)(21)(22)(23)(24)(25)(26). In these DNA prime, vector boost studies, typically polyfunctional T-cell responses, tier 1 neutralizing and nonneutralizing antibody responses, and even detection of effector T cells in the gut have been demonstrated, though responses are critically dependent on the insert, regimen, and time of sampling.…”

Mucosal Immunity and Vaccines Against Simian Immunodeficiency Virus and Human Immunodeficiency Virus

“…NYVAC, a recombinant replication-defective vaccinia vector, is one vector that is under consideration for advanced testing as a priming regimen, either alone or following HIV-1 plasmid DNA priming as part of the P5 correlates strategy (Figure 1). When tested following DNA HIV clade C prime, the NYVAC clade C HIV-1 vaccine candidate elicited both NYVAC-specific and low-frequency HIV-specific proliferating T cells in blood, rectum, and ileum mucosal tissues in most HIV-uninfected study participants (Perreau et al, 2011). These results suggest that this vaccine regimen could have some immune impact in preventing the spread of HIV-1 following mucosal exposure.…”