Venezuelan Equine Encephalitis Virus V3526 Vaccine RNA-Dependent RNA Polymerase Mutants Increase Vaccine Safety Through Restricted Tissue Tropism in a Murine Model.

Autor:	Haines CA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA., Campos RK; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA., Azar SR; Department of Pathology, University of Texas Medical Branch, Galveston, TX, 77555, USA., Warmbrod KL; Department of Pathology, University of Texas Medical Branch, Galveston, TX, 77555, USA., Kautz TF; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA., Forrester NL; Department of Pathology, University of Texas Medical Branch, Galveston, TX, 77555, USA., Rossi SL; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA.; Department of Pathology, University of Texas Medical Branch, Galveston, TX, 77555, USA.; Institute for Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX, 77555, USA.
Jazyk:	angličtina
Zdroj:	Zoonoses (Burlington, Mass.) [Zoonoses (Burlingt)] 2022; Vol. 2. Date of Electronic Publication: 2022 Jan 13.
DOI:	10.15212/zoonoses-2021-0016
Abstrakt:	Background: Venezuelan equine encephalitis virus (VEEV) is an arbovirus endemic to the Americas. There are no approved vaccines or antivirals. TC-83 and V3526 are the best-characterized vaccine candidates for VEEV. Both are live-attenuated vaccines and have been associated with safety concerns, albeit less so for V3526. A previous attempt to improve the TC-83 vaccine focused on further attenuating the vaccine by adding mutations that altered the error incorporation rate of the RNA-dependent RNA polymerase (RdRp). Methods: The research presented here examines the impact of these RdRp mutations in V3526 by cloning the 3X and 4X strains, assessing vaccine efficacy against challenge in adult female CD-1 mice, examining neutralizing antibody titers, investigating vaccine tissue tropism, and testing the stability of the mutant strains. Results: Our results show that the V3526 RdRp mutants exhibited reduced tissue tropism in the spleen and kidney compared to wild-type V3526, while maintaining vaccine efficacy. Illumina sequencing showed that the RdRp mutations could revert to wild-type V3526. Conclusions: The observed genotypic reversion is likely of limited concern because wild-type V3526 is still an effective vaccine capable of providing protection. Our results indicate that the V3526 RdRp mutants may be a safer vaccine design than the original V3526. Competing Interests: Conflicts of Interest The authors have no Conflicts of Interest to declare.
Databáze:	MEDLINE
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