Safety and immunogenicity of a modified pox vector-based HIV/AIDS vaccine candidate expressing Env, Gag, Pol and Nef proteins of HIV-1 subtype B (MVA-B) in healthy HIV-1-uninfected volunteers: A phase I clinical trial (RISVAC02)

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.…”

“…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).…”

“…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.…”

Langerin negative dendritic cells promote potent CD8 + T-cell priming by skin delivery of live adenovirus vaccine microneedle arrays

“…Herein, we show that a simple dissolvable microneedle array (MA) delivery system preserves the immunogenicity of vaccines encoded by live recombinant human adenovirus type 5 (rAdHu5 I nfection with HIV, malaria, and tuberculosis represents a global public health challenge. Candidate vaccines based on live recombinant viral vectors such as adenovirus (Ad), CMV, and poxvirus show promise through their ability to induce strong T-cell immunity (1)(2)(3). However, live vaccines are thermolabile, with loss in potency and safety in the absence of continuous cold chain storage and transport.…”

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

“…Modified vaccinia virus Ankara (MVA) has been used as a candidate smallpox vaccine and has had a favorable safety profile in Ͼ100,000 humans (8,10,11). Multiple immunizations with MVA are tolerated, and both T-cell and antibody responses are detected in the majority of volunteers (12)(13)(14)(15)(16). 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).…”