Evaluation of Multivalent Enterotoxigenic Escherichia coli Vaccine Candidate MecVax Antigen Dose-Dependent Effect in a Murine Model

Hyesuk Seo, Qiangde Duan, Ipshita Upadhyay, Weiping Zhang

Research output: Contribution to journalArticlepeer-review


There are no licensed vaccines against enterotoxigenic Escherichia coli (ETEC), a leading cause of children’s diarrhea and travelers’ diarrhea. Recently, protein-based vaccine candidate MecVax was demonstrated to induce functional antibodies against both ETEC toxins (heat-stable toxin [STa] and heat-labile toxin [LT]) and seven ETEC adhesins (CFA/I and CS1 to CS6) and to protect against ETEC clinical diarrhea or intestinal colonization preclinically. Those studies used intraperitoneal, intramuscular, and intradermal routes, and a dose range for MecVax protein antigens, toxoid fusion 3xSTaN12S-mnLTR192G/L211A, and adhesin CFA/I/II/IV MEFA has not been investigated. Here, we further characterized MecVax broad immunogenicity, utilizing a subcutaneous route, and examined vaccine dose-dependent antibody response effects and also antibody functional activities against ETEC enterotoxicity and bacterial adherence. Data showed that mice immunized subcutaneously with MecVax developed robust IgG responses to seven ETEC adhesins (CFA/I, as well as CS1 to CS6) and two toxins (STa and LT). At a subcutaneous dose of 25, 20, or 10 mg or at an intramuscular dose of 12, 6, or 3 mg, MecVax induced similar levels IgG responses to the targeted toxins and adhesins, and these antibodies exhibited equivalent functional activities against ETEC toxin enterotoxicity and bacterial adherence. Once the intramuscular dose was decreased to 1 mg, vaccine-induced antibodies were significantly reduced and no longer neutralized STa enterotoxicity. The results indicated that MecVax administered subcutaneously is broadly immunogenic and, at an intramuscular dose of 3 mg, can induce functional antitoxin and anti-adhesin antibodies in mice, providing instructive information for future vaccine dose studies in humans and accelerating MecVax vaccine development.

Original languageEnglish (US)
JournalApplied and environmental microbiology
Issue number17
StatePublished - Sep 2022


  • diarrhea
  • dose-dependent effect
  • dose-dependent study
  • enterotoxigenic Escherichia coli
  • ETEC
  • MecVax
  • vaccine

ASJC Scopus subject areas

  • Biotechnology
  • Food Science
  • Ecology
  • Applied Microbiology and Biotechnology


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