Comparison of the immunological responses and efficacy of gamma-irradiated V3526 vaccine formulations against subcutaneous and aerosol challenge with Venezuelan equine encephalitis virus subtype IAB

Abstract

We recently developed a gamma-irradiation method to inactivate V3526, a live-attenuated Venezuelan equine encephalitis virus (VEEV) vaccine candidate. Dosage and schedule studies were conducted to evaluate the immunogenicity and efficacy of gamma-irradiated V3526 (gV3526). Subcutaneous (SC) and low dosage intramuscular (IM) administration of gV3526 were highly effective in protecting mice against a SC challenge with VEEV IA/B Trinidad Donkey strain, but not against an equivalent aerosol challenge. More robust immune responses and increased protective efficacy were noted when the IM dosage of gV3526 was increased. IM administration of gV3526 formulated with either CpG or CpG plus Alhydrogel further augmented the immune response in mice and resulted in 100% protection against aerosol challenge.

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

“…2). Adjuvants such as CpG and Alhydrogel have been shown to enhance the antibody titers and protection in mice immunized with gamma irradiated V3526 [41]. These results are similar to those demonstrated by others with influenza and Ebola viruses where INA-inactivated viruses induced protective antibody response to respective viruses [32,33].…”

“…To evaluate if additional immunization and use of adjuvant increase the protection efficacy we gave an additional immunization dose and used Alhydrogel and CFA adjuvant in the second study. Alhydrogel is an approved adjuvant for human use and has been shown to increase the protection in gamma irradiated V3526 immunized mice [41]. CFA is also a potent adjuvant and was used to compare the response to Alhydrogel and to determine if use of adjuvant increases the protective efficacy.…”

Current Strategic Thinking for the Development of a Trivalent Alphavirus Vaccine for Human Use

“…However, safety remained a concern, because fever and flu-like symptoms were associated with human use of the vaccine. 27 An inactivated version of TC-83 (C84) is also available in North America but typically only recommended in high-risk areas. As a result, TC-83 continues to be produced in Colombia and Mexico for use in equids.…”

Virus Inactivation Using a High Dose of Gamma-Irradiation: A Possible Approach for Safer Vaccines Against Highly Infectious Agents

“…Interestingly, irradiation of frozen materials (at -80°C) has also been reported previously for inactivation of Venezuelan Equine Encephalitis Virus (VEEV) and Eastern Equine Encephalitis Virus (EEEV) for vaccine purposes using high doses of irradiation. VEEV irradiated with 50 kGy was reported to induce protection against subcutaneous and aerosol challenge with live virus in mice [14]. In addition, EEEV irradiated with 100 kGy was shown to induce both neutralising antibody responses and protection against aerosol challenge [15].…”