Yellow Fever: Role of Heterologous Flavivirus Immunity on Urban Emergence

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dc.contributor.advisorWeaver, Scott (sweaver@utmb.edu)
dc.contributor.committeeMemberPlante, Kenneth (ksplante@utmb.edu)
dc.contributor.committeeMemberVasilakis, Nikos (nivasila@utmb.edu)
dc.contributor.committeeMemberBeasley, David (dwbeasle@utmb.edu)
dc.contributor.committeeMemberDrumond, Betania (betaniadrumond@gmail.com)
dc.contributor.committeeMemberWeiskopf, Daniela (dweiskopf@lji.org)
dc.creatorShinde, Divya Pratik 1993-
dc.date.accessioned2024-07-15T15:08:02Z
dc.date.available2024-07-15T15:08:02Z
dc.date.created2024-08
dc.date.issued2024-08
dc.date.submittedAugust 2024
dc.date.updated2024-07-15T15:08:08Z
dc.description.abstractDuring the recent yellow fever (YF) epidemics in Brazil, human cases were attributed only to spillover infections via sylvatic mosquito transmission. Despite YF virus (YFV) transmission in major urban centers with insufficient vaccination coverage and abundant populations of the domestic vector, Aedes aegypti, there was no evidence of human-amplified transmission. Furthermore, the complete historic absence of YF in Asia, despite abundant Ae. aegypti and a completely immunologically naive human population represents a longstanding epidemiological enigma. We tested the hypothesis that pre-existing, heterologous flavivirus immunity, specifically from dengue (DENV) and Zika (ZIKV) viruses, limits YFV viremia and transmission by Ae. aegypti. We infected cynomolgus macaques with DENV or ZIKV, then challenged them 6-9 months later with YFV. We then measured viremia and disease, and allowed Ae. aegypti mosquitoes to feed during peak macaque viremia. Although prior heterologous immunity had variable effects on disease, DENV and ZIKV immunity consistently suppressed YFV viremia, leading to a significant reduction in Ae. aegypti infection and a lack of transmission potential. Next, we utilized an interferon α/β receptor knock-out mouse model to determine the role of pre-existing DENV-2 and ZIKV immunity in YF virus infection, and to determine mechanisms of cross-protection. We utilized African and Brazilian YF strains and found that DENV-2 and ZIKV immunity significantly suppresses YFV viremia in mice but did not consistently protect against disease outcome. Cross-protection appears to be mediated mainly by humoral immune responses. These studies underscore the importance to re-assess the risk of YF outbreak accounting for prior immunity from flaviviruses that are endemic.
dc.format.mimetypeapplication/pdf
dc.identifier.uri
dc.identifier.urihttps://hdl.handle.net/2152.3/12414
dc.language.isoEnglish
dc.subject.otherYellow Fever
dc.subject.otherDengue
dc.subject.otherZika
dc.subject.otherCross-protection
dc.subject.otherFlavivirus Immunity
dc.titleYellow Fever: Role of Heterologous Flavivirus Immunity on Urban Emergence
dc.typeThesis
dc.type.materialtext
thesis.degree.collegeUTMB Graduate School of Biomedical Sciences
thesis.degree.departmentMicrobiology and Immunology
thesis.degree.grantorThe University of Texas Medical Branch at Galveston
thesis.degree.nameDoctor of Philosophy
thesis.degree.schoolUniversity of Texas Medical Branch

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