Protective Immunity after DNA Vaccination against Pneumonic Plague Using a Needle-Free Jet Injection Platform 2253077

Abstract

Abstract Introduction Yersinia pestis (Yp), a facultative anaerobic gram-negative bacillus, causes plague, which if untreated has a case-fatality rate approaching 100% in primary pneumonic form. Yp is a known biothreat agent that can be aerosolized to potentially cause pneumonic plague outbreaks, and there is no licensed vaccine. Methods Here we used a pneumonic plague model in which BALB/c mice were exposed to aerosolized Yp strain CO92 to compare DNA vaccines encoding Yp antigens LcrV and F1 with established adjuvanted subunit vaccines based on LcrV and F1 proteins. DNA was delivered using a needle-free PharmaJet Tropis device recently modified for use in small animals, with no additional antigens or adjuvants. Results After two vaccine doses, mice vaccinated with F1 and/or LcrV DNA had cellular immunity comparable to the most effective subunit vaccines, as measured by cytokine secretion and counts of IFN-γ-producing splenocytes after ex vivo restimulation. LcrV DNA vaccination generated high anti-LcrV serum antibody titers, was effective at blocking bacterial replication, and conferred 60% survival in this model where all unvaccinated animals died within 4 days of challenge. The F1 DNA construct was not protective despite inducing T-cell immunity and was redesigned using information from the literature to address this deficiency. Conclusion These results are promising for the needle-free DNA/jet vaccine platform against bacterial pathogens, and studies of LcrV DNA combined with redesigned F1 DNA are in progress. Funding Source DTRA-JSTO Topic Categories Vaccines and Immunotherapy (VAC)