Genetically engineered, live attenuated vaccines for Venezuelan equine encephalitis: testing in animal models

Genetically engineered, live, attenuated vaccines protect nonhuman primates against aerosol challenge with a virulent IE strain of Venezuelan equine encephalitis virus

“…Although all monkeys from the three test groups had antibody responses to both IA/B and IE varieties of VEEV as measured by ELISA, only monkeys inoculated with IE1009 produced significant antibody responses to both varieties as measured by PRNT. V3526 induced an antibody response to IA/B-variety VEEV by both ELISA and PRNT in all eight monkeys, as previously reported [10]. By ELISA, serum IgG titers to VEEV-IE were detectable in all V3526-vaccinated monkeys but were reduced compared to responses to IA/B.…”

“…Peak serum N antibody titers were compared to the signs of disease to determine if these values correlated with protection of the macaques from aerosol challenge with VEEV-IE, as was shown previously for protection against challenge with VEEV-IA/B [10]. We found that serum N antibody titers to VEEV-IE failed to correlate significantly with fever response ( Fig.…”

“…V3526 has been shown to be safe [8] and to protect mice against subcutaneous or aerosol challenge with a virulent VEEV-IA/B [9]. Recently, Pratt et al [10] reported that out of several vaccine candidates examined, V3526 was best able to protect nonhuman primates against aerosol challenge with a virulent VEEV-IA/B.…”

Safety and protective efficacy of INA-inactivated Venezuelan equine encephalitis virus: Implication in vaccine development

“…An attenuated strain, V3526, which has a deletion mutation at the furin cleavage site between the E2 and E3 glycoproteins of the Trinidad donkey strain of VEEV [16] has been extensively evaluated as a VEEV vaccine candidate [17][18][19][20]. V3526 has excellent immunogenic activity, but also causes febrile illness and low level neurotropism in non human primates [17,18,[21][22][23]. In phase I clinical trial, V3526 induced a robust immune response; however, a high frequency of fever and a flu-like syndrome were reported which led to the cessation of the development of V3526 as a live attenuated vaccine [24,25].The residual virulence associated with the vaccine candidates has again focused the attention on the inactivated vaccine preparation.…”

Viral vectors for use in the development of biodefense vaccines

“…Reactogenicity of up to 40% in recipients of TC-83 warrants the development of a new VEEV vaccine [11,38]. A liveattenuated VEEV vaccine, V3526, was developed to replace TC-83 and is currently in scale-up production for eventual use in human clinical trials [39]. VEEV was weaponized and stockpiled by the U.S. before the 1972 BWC and is currently classified by NIAID as a category B pathogen [1].…”