The HIV/AIDS Vaccine Candidate MVA-B Administered as a Single Immunogen in Humans Triggers Robust, Polyfunctional, and Selective Effector Memory T Cell Responses to HIV-1 Antigens

Comparable Polyfunctionality of Ectromelia Virus- and Vaccinia Virus-Specific Murine T Cells despite Markedly DifferentIn VivoReplication and Pathogenicity

“…Therefore, by extension, the ability of VACV to induce polyfunctional T cells in humans likely contributes to its ability to stimulate highly effective immune responses against smallpox in immunized individuals. Ultimately, our findings provide further support for the use of VACV as a vaccine platform able to induce durable polyfunctional T cells (23,24,26).…”

Deletion of the Vaccinia Virus N2L Gene Encoding an Inhibitor of IRF3 Improves the Immunogenicity of Modified Vaccinia Virus Ankara Expressing HIV-1 Antigens

“…Recently, it has been demonstrated that VACV N2L encodes a nuclear inhibitor of IRF3 that blocks the IFN I signaling pathway at the intracellular level (59). As part of our effort to find out the immunomodulatory role of the VACV Bcl-2 family of proteins (30), here we deleted the VACV N2L gene from an MVA vector-based HIV/AIDS vaccine candidate termed MVA-B, which expresses HIV-1 Env, Gag, Pol, and Nef antigens from clade B (60) and has been well characterized in vitro (61,65), in mice (42,60,(62)(63)(64), in nonhuman primates (66), and in a phase I clinical trial in humans (12,14), showing that MVA-B is a promising HIV/ AIDS vaccine candidate that is safe, highly immunogenic, and able to induce broad, polyfunctional, and durable CD4 ϩ and CD8 ϩ T cell responses to HIV-1 antigens, together with humoral responses to Env.…”

“…MVA-B has been extensively studied in vitro and in different animal models (42,(60)(61)(62)(63)(64)(65)(66), where it triggers strong and durable immune responses to HIV-1 antigens. Furthermore, MVA-B was safe and highly immunogenic when tested in a phase I clinical trial with healthy human volunteers, inducing humoral responses to Env and HIV-1-specific CD4 ϩ and CD8 ϩ T cell responses that were high, broad, polyfunctional, and long-lasting (12,14). Moreover, a phase I clinical trial of HIV-1-infected patients on highly active antiretroviral therapy with MVA-B as an HIV/AIDS therapeutic vaccine is ongoing.…”

“…Numerous MVA vectors expressing different HIV-1 antigens have been produced and tested in human clinical trials (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25), revealing that MVA vectors are safe and elicit humoral and cellular immune responses to HIV-1 antigens (for reviews, see references 3, 6, and 7), regardless of its limited replication in human and most mammalian cell types. However, MVA still contains several immunomodulatory VACV genes that counteract the host antiviral innate immune response, particularly those genes encoding proteins that inhibit the Toll-like receptor (TLR) signaling pathway (26), an important route that plays a fundamental role in the defense against pathogens through the induction of proinflammatory cytokines and type I interferon (IFN) but also in modeling adaptive immune responses to patho-gens (27)(28)(29).…”

Kinetic and Phenotypic Analysis of CD8 + T Cell Responses after Priming with Alphavirus Replicons and Homologous or Heterologous Booster Immunizations

“…However, live attenuated pathogens are unsuitable vaccine candidates for chronic diseases due to the risk for establishing persistent infections. Alternatively, viral vectors such as replication-deficient adenovirus and poxvirus vectors can be used to elicit strong T cell-mediated immune responses and are therefore attractive candidates for the development of new vaccines (3)(4)(5).…”