Genetic Vaccines Directed Against Yersinia pestis
- *Abstract
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Invention: Vaccine against Yersinia pestis, delivered via viral vector.
Yersinia pestis is classified by the CDC as a Category A Biothreat; it was the cause of the infamous Black Death (or bubonic plague) that killed a third of Europe's population in the 14th century.
Although antibiotics can be used to treat Y. pestis infection if treated promptly, infection with Y. pestis causes significant morbidity, and it is still fatal for a high proportion of infected individuals. There are no available vaccines to prevent plague infection.
Ronald G. Crystal, M.D., and Julie L. Boyer, Ph.D., are developing strategies for such a vaccine, based on replication-deficient viruses, used to transfer to the individual a gene that will evoke host defenses to prevent Y. pestis infection.
The vaccine (currently named AdsecV), induces both antibodies and cellular immunity against Y. pestis, with protection induced in 1 to 2 weeks after a single administration. The fact that it takes only a single administration is very important, as all other candidate Y. pestis vaccines require at least 2 administrations, 4 weeks apart. The AdsecV vaccine has been tested in mice given a respiratory tract challenge with a fully virulent form of Y. pestis in comparison to 5 other candidate anti-Y. pestis vaccines developed in different laboratories funded by the National Institutes of Health. AdsecV was, by far, the most effective, and the only vaccine to protect 100% of the mice.
Significantly, the DNA for the antigen used in these experiments has been altered to include a sequence encoding a secretion signal. The sorting signal directs the expressed protein to endogenous antigen-presenting pathways, which enhances the ability of the vaccine to evoke a humoral immune response. The sequence has also been codon-optimized with human-preferred codons for optimal expression in humans.
Advantages
Rapid, high level immune response negates need for multiple dosing (shown in mice)
- *Licensing
- Brian J. Kellybjk44@cornell.edu212-746-6186
- 其他
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- (2006) Chiuchiolo MJ, et al. Protective immunity against respiratory tract challenge with Yersinia pestis in mice immunized with an adenovirus-based vaccine vector expressing V antigen. J Infect Dis. 194(9):1249-57.
- (2009) Sofer-Podesta C, et al. Adenovirus-mediated delivery of an anti-V antigen monoclonal antibody protects mice against a lethal Yersinia pestis challenge. Infect Immun. 77(4):1561-8.
- 国家/地区
- 美国
