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Utilizing the Antigen Capsid-Incorporation Strategy for the Development of Adenovirus Serotype 5-Vectored Vaccine Approaches
Published on: May 6, 2015
Protective immunity against botulism provided by a single dose vaccination with an adenovirus-vectored vaccine
Mingtao Zeng1, Qingfu Xu, Md Elias
1Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Box 672, 601 Elmwood Avenue, Rochester, NY 14642, USA. Mingtao_Zheng@urmc.rochester.edu
Abstract:
Botulinum neurotoxins cause botulism, a neuroparalytic disease in humans and animals. We constructed a replication-incompetent adenovirus encoding a synthesized codon-optimized gene for expression of the heavy chain C-fragment (H(C)50) of botulinum neurotoxin type C (BoNT/C). This recombinant human serotype 5 adenoviral vector (Ad5) was evaluated as a genetic vaccine candidate against botulism caused by BoNT/C in a mouse model. A one-time intramuscular injection with 10(5) to 2 x 10(7)pfu of adenoviral vectors elicited robust serum antibody responses against H(C)50 of BoNT/C as assessed by ELISA. Immune sera showed high potency in neutralizing the active BoNT/C in vitro. After a single dose of 2 x 10(7)pfu adenoviral vectors, the animals were completely protected against intraperitoneal challenge with 100 x MLD(50) of active BoNT/C. The protective immunity appeared to be vaccine dose-dependent. The anti-toxin protective immunity could last for at least 7 months without a booster injection. In addition, we observed that pre-existing immunity to the wild-type Ad5 in the host had no significant influence on the protective efficacy of vaccination. The data suggest that an adenovirus-vectored genetic vaccine is a highly efficient prophylaxis candidate against botulism.
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