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Browsing by Author "Weaver, Scott C."

Now showing 1 - 6 of 6
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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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    Enemy of My Enemy: A Novel Insect-Specific Flavivirus Offers a Promising Platform for a Zika Virus Vaccine
    Porier, Danielle L.; Wilson, Sarah N.; Auguste, Dawn I.; Leber, Andrew; Coutermarsh-Ott, Sheryl; Allen, Irving C.; Caswell, Clayton C.; Budnick, James A.; Bassaganya-Riera, Josep; Hontecillas, Raquel; Weger-Lucarelli, James; Weaver, Scott C.; Auguste, A. Jonathan (MDPI, 2021-10-07)
    Vaccination remains critical for viral disease outbreak prevention and control, but conventional vaccine development typically involves trade-offs between safety and immunogenicity. We used a recently discovered insect-specific flavivirus as a vector in order to develop an exceptionally safe, flavivirus vaccine candidate with single-dose efficacy. To evaluate the safety and efficacy of this platform, we created a chimeric Zika virus (ZIKV) vaccine candidate, designated Aripo/Zika virus (ARPV/ZIKV). ZIKV has caused immense economic and public health impacts throughout the Americas and remains a significant public health threat. ARPV/ZIKV vaccination showed exceptional safety due to ARPV/ZIKV’s inherent vertebrate host-restriction. ARPV/ZIKV showed no evidence of replication or translation in vitro and showed no hematological, histological or pathogenic effects in vivo. A single-dose immunization with ARPV/ZIKV induced rapid and robust neutralizing antibody and cellular responses, which offered complete protection against ZIKV-induced morbidity, mortality and in utero transmission in immune-competent and -compromised murine models. Splenocytes derived from vaccinated mice demonstrated significant CD4+ and CD8+ responses and significant cytokine production post-antigen exposure. Altogether, our results further support that chimeric insect-specific flaviviruses are a promising strategy to restrict flavivirus emergence via vaccine development.
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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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    Large scale complete genome sequencing and phylodynamic analysis of eastern equine encephalitis virus reveal source-sink transmission dynamics in the United States
    Tan, Yi; Lam, Tommy Tsan-Yuk; Heberlein-Larson, Lea A.; Smole, Sandra C.; Auguste, A. Jonathan; Hennigan, Scott; Halpin, Rebecca A.; Fedorova, Nadia; Puri, Vinita; Stockwell, Timothy B.; Shilts, Meghan H.; Andreadis, Theodore G.; Armstrong, Philip M.; Tesh, Robert B.; Weaver, Scott C.; Unnasch, Thomas R.; Ciota, Alexander T.; Kramer, Laura D.; Das, Suman R. (American Society for Microbiology, 2018-04-04)
    Eastern equine encephalitis virus (EEEV) has a high case-fatality rate in horses and humans, and Florida has been hypothesized to be the source of EEEV epidemics for the northeastern United States. To test this hypothesis, we sequenced complete genomes of 433 EEEV strains collected within the United States from 1934 to 2014. Phylogenetic analysis suggested EEEV evolves relatively slowly and that transmission is enzootic in Florida, characterized by higher genetic diversity and long-term local persistence. In contrast, EEEV strains in New York and Massachusetts were characterized by lower genetic diversity, multiple introductions, and shorter local persistence. Our phylogeographic analysis supported a source-sink model in which Florida is the major source of EEEV compared to the other localities sampled. In sum, this study revealed the complex epidemiological dynamics of EEEV in different geographic regions in the United States and provided general insights into the evolution and transmission of other avian mosquito-borne viruses in this region.
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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.
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    Sylvatic Mosquito Diversity in Kenya—Considering Enzootic Ecology of Arboviruses in an Era of Deforestation
    Eastwood, Gillian; Sang, Rosemary C.; Lutomiah, Joel; Tunge, Philip; Weaver, Scott C. (MDPI, 2020-06-03)
    As new and re-emerging vector-borne diseases are occurring across the world, East Africa represents an interesting location, being the origin of several arboviruses with a history of urbanization and global spread. Rapid expansion of urban populations and alteration of natural habitats creates the opportunity for arboviruses to host-switch from wild, sylvatic hosts or vectors into urban transmission affecting human populations. Although mosquito surveillance regularly takes place in urban areas of Kenya, for example identifying vectors of dengue virus or malaria viruses, little work has been carried out to determine the distribution and abundance of sylvatic vectors. Here, we describe the mosquito vector species and diversity collected at twelve forest habitats of rural Kenya. We conducted arbovirus screening of over 14,082 mosquitoes (47 species, 11 genera) as 1520 pools, and detected seven viruses (six bunyaviruses, and one flavivirus-bunyavirus co-infection) isolated from pools of Aedes dentatus, Anopheles funestus, Culex annulioris, and Cx. vansomereni. Awareness of sylvatic vector species and their location is a critical part of understanding the ecological foci and enzootic cycling of pathogens that may be of concern to public, animal or wildlife health. As natural ecosystems come under anthropogenic pressures, such knowledge can inform us of the One Health potential for spillover or spillback leading to outbreaks, and assist in vector control strategies.