Genetic Vaccines Directed Against Bacterial Exotoxins
- Others
-
- (2003) Tan, Y., et al. Protective immunity evoked against anthrax lethal toxin after a single intramuscular administration of an adenovirus-based vaccine encoding humanized protective antigen. Hum. Gene Ther. 14:1673-1682.
- (2005) Hashimoto M, et al. Induction of protective immunity to anthrax lethal toxin with a nonhuman primate adenovirus-based vaccine in the presence of preexisting anti-human adenovirus immunity. Infect Immun. 3(10):6885-91
- (2005) Kasuya K, et al. Passive immunotherapy for anthrax toxin mediated by an adenovirus expressing an anti-protective antigen single-chain antibody. Mol Ther. 11(2):237-44.
- (2008) Boot EP, Parren PW. Genetic vaccination: one-shot shopping for immediate and sustained protection. Mol Ther. 2008 Jan;16(1):6-7. Comment on Mol Ther. 2008 Jan;16(1):203-9.
- (2008) De BP, et al. Rapid/sustained anti-anthrax passive immunity mediated by co-administration of Ad/AAV. Mol Ther. 16(1):203-9. (has comment)
- *Abstract
-
Currently available anthrax vaccines are effective, but require a rigorous and long dosing schedule, and have aroused some controversy due to their potential side effects.
Researchers at the Weill Cornell Medical College are developing a DNA vaccine against anthrax that can be used therapeutically in combination with antibiotics, or as a prophylaxis. The vaccine provides a gene transfer vector comprising a nucleic acid sequence that encodes one or more of the three proteins that combine to produce the exotoxins of B. anthracis: protective antigen (PA), lethal factor (LF), and edema factor (EF). Research to date has focused on PA, as it is a component of both exotoxins. PA has been delivered to mice using both recombinant serotype 5 adenovirus vector (Ad5) and - because 35 to 50% of humans have preexisting neutralizing antibodies against Ad5 -- nonhuman primate-derived serotype AdC7, against which humans do not have immunity. Single-dose administrations of PA in either vector produced a strong and lasting immune response, but the AdC7 vector was able to produce a response in mice with immunity to Ad5, whereas Ad5 failed to do so.
Significantly, the DNA for PA used in these experiments has been altered to include coding for a human sorting signal peptide. 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.
Advantages
- Rapid, high level immune response negates need for multiple dosing (shown in mice)
- May have fewer side effects than current vaccines
- *Licensing
- Brian J. Kellybjk44@cornell.edu212-746-6186
- Country/Region
- USA
