Poster No. 31
Title:
Detection and Prevention of Viral Infections: Virus Research at Tufts Cummings School of Veterinary
Medicine.
Names of Authors:
John E. Herrmann and David W. Brown
Department:
Department of Biomedical Sciences, Tufts Cummings School of Veterinary Medicine
Abstract:
The virology research program at the Veterinary School is currently focused on two areas, 1) Development
of oral, non-infectious rotavirus vaccines and factors in immunity to these viruses, and 2) new approaches
for detection of enteric viruses in clinical samples.
Oral, non-infectious rotavirus vaccines. The goal of these studies is to develop new approaches to rotavirus
vaccines that will provide the basis for human rotavirus vaccination. Rotaviruses are the major cause of
severe acute diarrhea in children, resulting in an estimated 400,000 to 600,000 deaths per year, and the live,
oral vaccines available to date have not been effective in developing countries where the need is the
greatest. We are studying the use of orally delivered DNA vaccines to provide protective immunity, and
the use of rotavirus genes in Bacillus subtilis spores as a delivery method. In previous studies we showed
that protective immunity in mice was obtained by oral administration of rotavirus DNA vaccines
encapsulated in poly (lactide-co-glycolide) microparticles in mice. DNA vaccines against both neutralizing
and non-neutralizing rotavirus antigens were effective in providing protection (Journal of Virology 72:
5757-5761, 1998; Virology 259:148-153, 1999). These and related studies are ongoing. More recently, we
have started studies in collaboration with Dr. Linc Sonenshein at Tufts Medical School that involves the
use of B. subtilis spores to deliver vaccines against infectious agents, funded by a Gates Grand Challenge
grant. Use of B. subtilis spores as oral vaccine delivery agents takes advantage of the high natural
resistance of spores to heat, dryness and other environmental stresses, thus circumventing the need for a
cold chain and specialized storage facilities. For the rotavirus studies, genes that we used for the rotavirus
DNA vaccines are being utilized in B. subtilis constructs. The need for improved rotavirus vaccines is a
continuing one and immunization with DNA or B. subtilis spore vaccines that express specific rotaviral
proteins offers a new approach to vaccination against rotaviruses.
Detection of enteric viruses. Under NIH funding for food and water borne pathogens, our goal is to create a
comprehensive diagnostic panel for detecting enteric viruses in clinical samples. The panel includes agents
classified as NIAID Biodefense priority category "B" viruses, the human caliciviruses and hepatitis A virus,
and will distinguish these from other enteric viruses, including astroviruses, rotavirus, and enteric
adenoviruses. Human caliciviruses (noroviruses) are well-recognized causes of foodborne and waterborne
Poster No. 31
gastroenteritis; astroviruses have been implicated in major outbreaks of foodborne gastroenteritis, are
similar in physicochemical properties to caliciviruses, and serve as cultivatable models for the noroviruses.
We are developing RT-PCR assays for detection of all known strains of these enteric viruses in clinical
samples and will establish a DNA microarray to characterize products obtained in RT-PCR assays. As a
secondary goal, using reagents and techniques previously developed by us, we are applying monoclonal
antibody enzyme immunoassays in a protein microarray format for detection of these viruses in clinical
samples. This will be a rapid screen to complement the RT-PCR. Successful completion of the research
proposed will afford a comprehensive approach and provide the necessary reagents for specific and rapid
diagnosis of enteric virus infections. This is essential to implement control measures and to identify sources
of an outbreak.