Broad Immunogenicity of a Multigene, Multiclade HIV‐1 DNA Vaccine Boosted with Heterologous HIV‐1 Recombinant Modified Vaccinia Virus Ankara

Abstract

Background A human immunodeficiency virus (HIV) vaccine that limits disease and transmission is urgently needed. This clinical trial evaluated the safety and immunogenicity of an HIV vaccine that combines a plasmid-DNA priming vaccine and a modified vaccinia virus Ankara (MVA) boosting vaccine. Methods Forty healthy volunteers were injected with DNA plasmids containing gp160 of HIV-1 subtypes A, B, and C; rev B; p17/p24 gag A and B, and RTmut B by use of a needle-free injection system. The vaccine was administered intradermally or intramuscularly, with or without recombinant granulocyte macrophage colony-stimulating factor, and boosted with a heterologous MVA containing env, gag, and pol of CRF01A_E. Immune responses were monitored with HIV-specific interferon (IFN)-γ and interleukin (IL)–2 ELISpot and lymphoproliferative assays (LPAs). Results Vaccine-related adverse events were mild and tolerable. After receipt of the DNA priming vaccine, 11 (30%) of 37 vaccinees had HIV-specific IFN-γ responses. After receipt of the MVA boosting vaccine, ELISpot assays showed that 34 (92%) of 37 vaccinees had HIV-specific IFN-γ responses, 32 (86%) to Gag and 24 (65%) to Env. IFN-γ production was detected in both the CD8+ T cell compartment (5 of 9 selected vaccinees) and the CD4+ T cell compartment (9 of 9). ELISpot results showed that 25 (68%) of 37 vaccinees had a positive IL-2 response and 35 (92%) of 38 had a positive LPA response. Of 38 subjects, a total of 37 (97%) were responders. One milligram of HIV-1 DNA administered intradermally was as effective as 4 mg administered intramuscularly in priming for the MVA boosting vaccine. Conclusion This HIV-DNA priming–MVA boosting approach is safe and highly immunogenic. Trials registration International Standard Randomised Controlled Trial number: ISRCTN32604572.

Dendritic cell based vaccines for HIV infection

“…9 Although some preventive vaccines have demonstrated low immunogenicity used alone, they are shown to be effective as a prime-boost strategy. 70,71 Similarly, it has been shown in animal models that heterologous prime-boost immunization with viral vectors (Modified Vaccinia Ankara: MVA) and DC-targeting protein-based vaccines is a promising vaccination approach to optimize humoral and cellular immunity for therapeutic applications against AIDS. 72 These primeboost strategies deserve to be tested in the therapeutic vaccine setting to test whether they improve both HIV specific immune responses and virological responses as compared with one immungen alone.…”

Boosting Functional Avidity of CD8 + T Cells by Vaccinia Virus Vaccination Depends on Intrinsic T-Cell MyD88 Expression but Not the Inflammatory Milieu

“…A regimen of priming with recombinant DNA and boosting with a viral vector has been shown to elicit strong T-cell immune responses (1)(2)(3); thus, it is becoming one of the most prevalent vaccine strategies (4). Several regimens have been widely adopted, including the DNA prime-vaccinia vector vaccine boost and the DNA prime-adenoviral vector vaccine boost (5).…”

Superior Induction of T Cell Responses to Conserved HIV-1 Regions by Electroporated Alphavirus Replicon DNA Compared to That with Conventional Plasmid DNA Vaccine

“…Three veterinary DNA vaccines have been licensed for use in dogs, salmon, and horses, demonstrating that DNA vaccines are capable of inducing protective immunity (8, 48). In humans, plasmid DNA vaccines have been shown to be safe and well tolerated in thousands of volunteers (14,41,48); however, their strong immunogenicity observed in smaller animals does not transfer to primates, including humans. Thus, the potency of DNA vaccines in humans must be significantly improved for the vaccines to become a practical and commercially attractive health care tool.…”