Studies of a prophylactic HIV-1 vaccine candidate based on modified vaccinia virus Ankara (MVA) with and without DNA priming: Effects of dosage and route on safety and immunogenicity

Systemic DNA immunization against ovine lentivirus using particle-mediated epidermal delivery and modified vaccinia Ankara encoding the gag and/or env genes

“…Significant induction has usually required the use of viral boosting vectors, numerous plasmid boosts or high plasmid doses. MVA is often used as a viral vector to provide an efficient protein boost [37] and [38]. However, in our study we could not discern a significant boosting effect of MVA for CTLs.…”

The TNFR family members OX40 and CD27 link viral virulence to protective T cell vaccines in mice

“…Similarly, MVA expressing the GAG protein (consensus of HIV-1 clade A) and several immunodominant CD8 + T cell epitopes resulted in responses detectable in only 17% of individuals (34). A smaller study using the same vaccines at a higher dose showed enhanced immunogenicity (40% response), but the responses induced were exclusively the result of CD4 + T cells (7). As previously shown by Morgan et al (17) and supported by our present data, the virulence of a VACV vector also critically influences the protective efficacy of the recombinant vaccine.…”

“…However, there is considerable literature acknowledging that highly replicative viruses are better at inducing CD8 + T cell responses. Animal and nonhuman primate studies have suggested that multiple dosing, or higher dosing, with replication-incompetent highly attenuated poxviruses is required to achieve T cell responses, and sometimes antibody responses, comparable to those elicited by replicationcompetent or highly virulent poxviruses (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). Although this is logically related to antigen load or the persistence of antigen to stimulate CD8 + T cells, the effect of reduced virulence on immunogenicity becomes a major issue when attempting to derive a truly effective vaccine that incorporates attenuated vectors.…”

“…These include modified VACV Ankara (MVA) (14), a variant of Lister strain LC16m8; ACAM1000/2000, derived from New York City Board of Health strain NYCBOH; the highly deleted Copenhagen VACV strain derivative NYVAC; and attenuated canarypox virus (ALVAC). Although some vectors given by certain routes might result in strong CD8 + T cell responses, the literature also suggests there is variability in the levels of CD8 + T cell immunity, raising the question of what determines induction of optimal CD8 + T cell responses (2,(7)(8)(9)(10)(15)(16)(17). Using several clinically relevant natural and recombinant VACV variants, we show here a quantitative difference in CD8 + T cell immunity elicited depending on the virus and immunization route, with only the most virulent VACVs promoting protective populations of memory CD8 + T cells.…”

Phase I Safety and Immunogenicity Trial of Plasmodium vivax CS Derived Long Synthetic Peptides Adjuvanted with Montanide ISA 720 or Montanide ISA 51

“…These adjuvants were selected because they form stable water-in-oil emulsions and induced high antibody levels that lasted for up to 1 year in mice, rabbits, and monkeys in previous studies using recombinant malaria proteins. 23,[26][27][28][29][30][31][32] More recently, a recombinant P. vivax CS protein produced in Escherichia coli and formulated in Montanide ISA 720 showed to be highly immunogenic in mice. 33 Several phase I clinical trials have been conducted using different malaria vaccine antigens in which these two adjuvants have been able to stimulate both humoral and cellular immune responses.…”