A replicating single-cycle adenovirus vaccine effective against clostridium difficile

William E. Matchett, Stephanie Anguiano-Zarate, Goda Baddage Rakitha Malewana, Haley Mudrick, Melissa Weldy, Clayton Evert, Alexander Khoruts, Michael Sadowsky, Michael A. Barry

Research output: Contribution to journalArticlepeer-review

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’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.

Original languageEnglish (US)
Article number470
Pages (from-to)1-15
Number of pages15
JournalVaccines
Volume8
Issue number3
DOIs
StatePublished - 2020

Keywords

  • Adenovirus
  • Animal models
  • Clostridium difficile
  • Single-cycle
  • Vaccine

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Drug Discovery
  • Infectious Diseases
  • Pharmacology (medical)

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