Department of Microbiology & Immunology

Phone: (409) 266-6500
Fax: (409) 266-6810
Email: sweaver@utmb.edu

Education: PhD, 1994, University of California, San Diego, La Jolla, CA
MS, 1982, Cornell University, Ithaca, NY
BS, 1979, The College of William and Mary, Williamsburg, VA

Overview: Ecology, epidemiology, evolution, and pathogenesis of arboviral diseases; vaccine development.

Research Interests

Dr. Weaver’s research focuses on the pathogenesis, ecology, and genetics of arthropod-borne viruses, especially alphaviruses and dengue, and on biodefense including vaccine development. His work focuses primarily on the encephalitic alphaviruses, including Venezuelan (VEEV), eastern (EEEV) and western equine encephalitis viruses (WEEV), which are important, naturally emerging pathogens as well as highly developed biological weapons.

1. Venezuelan equine encephalitis virus (VEEV) is responsible for several recent human and equine outbreaks in northern South America and Mexico. We have shown that epidemic VEEV strains evolved very recently from avirulent, enzootic viruses that circulate in sylvatic foci involving rodent hosts and mosquito vectors. We are using ecological studies, laboratory transmission experiments, and reverse genetic approaches to study VEE emergence at the molecular, ecological and geographic levels. The latter approach relies on satellite imagery to map the locations of enzootic VEE viruses with emergence potential. This project involves collaborations with scientists in Venezuela, Colombia and Mexico, and at the USDA.
2. We use similar approaches to those described above for VEEV to study retrospectively the emergence of urban dengue and chikungunya viruses from zoonotic progenitors that use non-human primate reservoir hosts and sylvatic mosquito vectors. Animal models are used to examine the ability of sylvatic strains to replicate in humans, and antigenic characterizations are conducted to determine the ability of these zoonotic cycles to emerge into the human population in the face of natural or vaccine-induced immunity. Human disease surveillance and mosquito vector ecology studies are undertaken in eastern Senegal to determine the extent of human contact by the ancestral, sylvatic strains. This project involves a collaboration with scientists at the Institut Pasteur in Dakar.
3. The efficiency of mosquito infections by arboviruses can be an important determinant of disease emergence. Our recent work has demonstrated that enzootic, sylvatic, rodent-borne, subtype ID VEEV strains periodically adapt for efficient equine replication and high titer viremia induction to generate epidemic strains and amplification cycles that spillover to infect humans. We are characterizing infection of Aedes taeniorhynchus Culex taeniopus by both enzootic and epidemic VEEV strains in order to understand more completely the mechanisms of viral adaptation to this vector. Using a unique set of fluorescent protein- and luciferase-expressing enzootic and epidemic VEEV replicon particles and viruses combined with traditional and molecular genetic methods, we examine infection of the mosquito midgut, believed to be the portal of entry, as well as downstream target tissues and organs including the salivary glands. These viruses and replicon particles are also being used to characterize the "barriers" to infection and dissemination that are overcome by epidemic VEEV strains for efficient transmission, and reverse genetic approaches will identify the determinants of the efficient infection VEEV phenotype.
4. In collaboration with Dr. Ilya Frolov, chimeric alphavirus vaccine candidates are being developed against VEEV, eastern (EEEV), and western equine encephalitis viruses (WEEV), as well as the recently emerged chikungunya virus. The safety and efficacy of these vaccine candidates are being tested in mouse and primate models in collaboration with the Tulane National Primate Research Center. Transmission potential is also being evaluated with experimental infection of mosquito vectors, and novel genetic strategies are being developed to prevent vaccine strain transmission.
5. We are also developing a platform technology capable of rapidly producing virus-like particle vaccines, in a non-mammalian bacterial system, that protect people against infection by emerging or biothreat viruses. This project is exploiting recent advances by the Dow Chemical Company in a high expression, bacterial protein-based technology for the synthesis of foreign antigenic epitopes in cowpea chlorotic mottle virus (CCMV) virus-like particles (VLPs) to develop this platform. We are using Eastern equine encephalitis virus (EEEV), which has received very little antigenic characterization to evaluate the ability of the new platform technology to rapidly produce vaccine candidates against poorly characterized or newly discovered viruses. Envelope protein epitope libraries from EEEV cDNA are expressed in the bacterial VLP system, as a high throughput screening method to identify suitable vaccine candidates that are recognized by antibodies from immune animals. Epitopes found to provide protection will eventually be tested in larger animals prior to moving into a pre-clinical non-human primate test.

Recent Publications

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