In principle, most viral infections can be prevented by effective and timely vaccination. In the past several decades however, the rapid emergence and spread into new geographical areas of viruses such as dengue, West Nile virus, HIV, and the highly pathogenic avian influenzas has outpaced the development of preventative vaccines. The major focus of the research in the Laboratory of Vaccine Vector Immunology is to develop novel vaccines based on recombinant viruses for the prevention of viral diseases and to better characterize the vaccine-induced immune responses that confer long-lasting protection. Current projects in this lab include:
Development of short-acting influenza vaccines based on vesicular stomatitis virus
Our lab has been successful in developing novel influenza vaccines based on vesicular stomatitis virus (VSV). VSV is a highly immunogenic and adaptable vaccine vector, which has been used to generate vaccines against many infectious diseases. We have shown that an rVSV expressing the influenza hemagglutinin is effective both as a prophylactic, and as a short-acting emergency influenza vaccine. Ongoing projects are to develop this as a vaccine against highly pathogenic avian influenza, and to encode conserved structural antigens in the vaccine, with the goal of generating heterologous protection against divergent influenzas.
Development of less reactogenic viral vaccine vectors
We have determined that reactogenic side-effects caused by rVSV immunization are linked to the production of inflammatory cytokines. Ongoing projects will attempt to ameliorate reactogenic side effects by encoding cytokine “traps” or other suppressors in the vaccine vectors, with the goal of locally suppressing the inflammatory response.
Characterization of novel Type I IFNs from pteropid bats
Large bats of the genus Pteropus are the reservoir species for many emerging viruses, including Ebola and Marburg virus, Nipah and Hendra virus, and SARS CoV. These viruses are distinguished from other zoonotic pathogens by their extreme pathogenicity in humans. We hypothesize that the innate immune system of pteropid bats has evolved with the viruses for which they are the reservoir host in such a way as to render the viruses less pathogenic in those animals. Specifically, we predict that pteropid bats have evolved a superior Type I IFN system capable of responding to and containing these viruses. Because bat immunology is a completely new field, we have partnered with Dr. Thomas Kepler (Duke Computational Biology) to identify and characterize novel Type I IFNs from pteropid bats. We have completed our computational analysis, and are now in the process of verifying experimentally the presence and function of the IFN genes.