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A Replicating Single-Cycle Adenovirus Vaccine Effective against Clostridium difficile
- Source :
- Vaccines, Volume 8, Issue 3, Vaccines, Vol 8, Iss 470, p 470 (2020)
- Publication Year :
- 2020
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2020.
-
Abstract
- Clostridium difficile causes nearly 500,000 infections and nearly 30,000 deaths each year in the U.S., which is estimated to cost $4.8 billion. C. difficile infection (CDI) arises from bacteria colonizing the large intestine and releasing two toxins, toxin A (TcdA) and toxin B (TcdB). Generating humoral immunity against C. difficile&rsquo<br />s toxins provides protection against primary infection and recurrence. Thus, a vaccine may offer the best opportunity for sustained, long-term protection. We developed a novel single-cycle adenovirus (SC-Ad) vaccine against C. difficile expressing the receptor-binding domains from TcdA and TcdB. The single immunization of mice generated sustained toxin-binding antibody responses and protected them from lethal toxin challenge for up to 38 weeks. Immunized Syrian hamsters produced significant toxin-neutralizing antibodies that increased over 36 weeks. Single intramuscular immunization provided complete protection against lethal BI/NAP1/027 spore challenge 45 weeks later. These data suggest that this replicating vaccine may prove useful against CDI in humans.
- Subjects :
- 0301 basic medicine
030106 microbiology
Immunology
Clostridium difficile toxin A
lcsh:Medicine
Clostridium difficile toxin B
03 medical and health sciences
vaccine
Drug Discovery
medicine
Pharmacology (medical)
Pharmacology
biology
business.industry
single-cycle
lcsh:R
adenovirus
Clostridium difficile
biology.organism_classification
Virology
animal models
Adenovirus vaccine
030104 developmental biology
Infectious Diseases
Immunization
Humoral immunity
biology.protein
Antibody
business
Bacteria
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 2076393X
- Database :
- OpenAIRE
- Journal :
- Vaccines
- Accession number :
- edsair.doi.dedup.....815168baf26801e26024afd3061bc1b0
- Full Text :
- https://doi.org/10.3390/vaccines8030470