A Replicating Single-Cycle Adenovirus Vaccine Effective against Clostridium difficile

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 hum...

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Bibliographic Details
Published in:Vaccines (Basel) 2020-08, Vol.8 (3), p.470
Main Authors: Matchett, William E., Anguiano-Zarate, Stephanie, Malewana, Goda Baddage Rakitha, Mudrick, Haley, Weldy, Melissa, Evert, Clayton, Khoruts, Alexander, Sadowsky, Michael, Barry, Michael A.
Format: Article
Language:English
Subjects:
adenovirus
Adenoviruses
Aluminum
animal models
Animal welfare
Antibodies
Antigens
Binding
Clinical trials
Clostridium difficile
Cytotoxicity
Hamsters
Humoral immunity
Immunization
Intestine
Laboratory animals
Large intestine
Proteins
Replication
single-cycle
Toxin A
Toxin B
Toxins
vaccine
Vaccines
Viruses
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Summary: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’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.
ISSN:2076-393X
2076-393X
DOI:10.3390/vaccines8030470