Browsing by Author "Wang, Tian"

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    Effects of Chikungunya virus immunity on Mayaro virus disease and epidemic potential
    Webb, Emily M.; Azar, Sasha R.; Haller, Sherry L.; Langsjoen, Rose M.; Cuthbert, Candace E.; Ramjag, Anushka T.; Luo, Huanle; Plante, Kenneth; Wang, Tian; Simmons, Graham; Carrington, Christine V. F.; Weaver, Scott C.; Ross, Shannan L.; Auguste, A. Jonathan (Springer Nature, 2019)
    Mayaro virus (MAYV) causes an acute febrile illness similar to that produced by chikungunya virus (CHIKV), an evolutionary relative in the Semliki Forest virus complex of alphaviruses. MAYV emergence is typically sporadic, but recent isolations and outbreaks indicate that the virus remains a public health concern. Given the close phylogenetic and antigenic relationship between CHIKV and MAYV, and widespread distribution of CHIKV, we hypothesized that prior CHIKV immunity may affect MAYV pathogenesis and/or influence its emergence potential. We pre-exposed immunocompetent C57BL/6 and immunocompromised A129 or IFNAR mice to wild-type CHIKV, two CHIKV vaccines, or a live-attenuated MAYV vaccine, and challenged with MAYV. We observed strong cross-protection against MAYV for mice pre-exposed to wild-type CHIKV, and moderately but significantly reduced cross-protection from CHIKV-vaccinated animals. Immunity to other alphavirus or flavivirus controls provided no protection against MAYV disease or viremia. Mechanistic studies suggested that neutralizing antibodies alone can mediate this protection, with T-cells having no significant effect on diminishing disease. Finally, human sera obtained from naturally acquired CHIKV infection cross-neutralized MAYV at high titers in vitro. Altogether, our data suggest that CHIKV infection can confer cross-protective effects against MAYV, and the resultant reduction in viremia may limit the emergence potential of MAYV.
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    Isolation of a novel insect-specific flavivirus with immunomodulatory effects in vertebrate systems
    Auguste, A. Jonathan; Langsjoen, Rose M.; Porier, Danielle L.; Erasmus, Jesse H.; Bergren, Nicholas A.; Bolling, Bethany G.; Luo, Huanle; Singh, Ankita; Guzman, Hilda; Popov, Vsevolod L.; da Rosa, Amelia P. A. Travassos; Wang, Tian; Kang, Lin; Allen, Irving C.; Carrington, Christine V. F.; Tesh, Robert B.; Weaver, Scott C. (2021-10)
    We describe the isolation and characterization of a novel insect-specific flavivirus (ISFV), tentatively named Aripo virus (ARPV), that was isolated from Psorophora albipes mosquitoes collected in Trinidad. The ARPV genome was determined and phylogenetic analyses showed that it is a dual host associated ISFV, and clusters with the main mosquito-borne flaviviruses. ARPV antigen was significantly cross-reactive with Japanese encephalitis virus serogroup antisera, with significant cross-reactivity to Ilheus and West Nile virus (WNV). Results suggest that ARPV replication is limited to mosquitoes, as it did not replicate in the sandfly, culicoides or vertebrate cell lines tested. We also demonstrated that ARPV is endocytosed into vertebrate cells and is highly immunomodulatory, producing a robust innate immune response despite its inability to replicate in vertebrate systems. We show that prior infection or coinfection with ARPV limits WNV-induced disease in mouse models, likely the result of a robust ARPV-induced type I interferon response.
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    Optimized production and immunogenicity of an insect virus-based chikungunya virus candidate vaccine in cell culture and animal models
    Adam, Awadalkareem; Luo, Huanle; Osman, Samantha R.; Wang, Binbin; Roundy, Christopher M.; Auguste, A. Jonathan; Plante, Kenneth S.; Peng, Bi-Hung; Thangamani, Saravanan; Frolova, Elena I.; Frolov, Ilya; Weaver, Scott C.; Wang, Tian (2021-01-01)
    A chimeric Eilat/ Chikungunya virus (EILV/CHIKV) was previously reported to replicate only in mosquito cells but capable of inducing robust adaptive immunity in animals. Here, we initially selected C7/10 cells to optimize the production of the chimeric virus. A two-step procedure produced highly purified virus stocks, which was shown to not cause hypersensitive reactions in a mouse sensitization study. We further optimized the dose and characterized the kinetics of EILV/CHIKV-induced immunity. A single dose of 10(8) PFU was sufficient for induction of high levels of CHIKV-specific IgM and IgG antibodies, memory B cell and CD8(+) T cell responses. Compared to the live-attenuated CHIKV vaccine 181/25, EILV/CHIKV induced similar levels of CHIKV-specific memory B cells, but higher CD8(+) T cell responses at day 28. It also induced stronger CD8(+), but lower CD4(+) T cell responses than another live-attenuated CHIKV strain (CHIKV/IRES) at day 55 post-vaccination. Lastly, the purified EILV/CHIKV triggered antiviral cytokine responses and activation of antigen presenting cell (APC)s in vivo, but did not induce APCs alone upon in vitro exposure. Overall, our results demonstrate that the EILV/CHIKV vaccine candidate is safe, inexpensive to produce and a potent inducer of both innate and adaptive immunity in mice.