Citations 1
A Replicating Single-Cycle Adenovirus Vaccine Effective against Clostridium difficile
Matchett, William E. , Anguiano-Zarate, Stephanie S., Malewana, Goda Baddage Rakitha , Mudrick, Haley , Weldy, Melissa, Evert, Clayton , Khoruts, Alexander , Sadowsky, Michael J. , Barry, Michael A. , Anguiano-Zarate, Stephanie, Barry, Michael A
Vaccines | August 23, 2020 | Volume: 8 | Issue: 3 | Pages: 470
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.