Intramuscularly Administered Enterotoxigenic Escherichia coli (ETEC) Vaccine Candidate MecVax Prevented H10407 Intestinal Colonization in an Adult Rabbit Colonization Model

Abstract

An effective ETEC vaccine would prevent hundreds of millions of diarrhea clinical cases and save nearly 100,000 lives annually. MecVax, a protein-based injectable multivalent ETEC vaccine candidate, has been shown for the first time to induce functional antibodies against both ETEC enterotoxins (STa, LT) produced by all ETEC strains and seven ETEC adhesins (CFA/I, CS1 to CS6) expressed by ETEC strains causing a majority of ETEC diarrhea clinical cases and the moderate-to-severe cases.

A Polyvalent Adhesin–Toxoid Multiepitope-Fusion-Antigen-Induced Functional Antibodies against Five Enterotoxigenic Escherichia coli Adhesins (CS7, CS12, CS14, CS17, and CS21) but Not Enterotoxins (LT and STa)

“…Two weeks after the second booster, all rabbits were orogastrically challenged with ETEC field isolate JF2101 (CS21 and STa) to assess adhesin MEFA-IIb in vivo protection against ETEC intestinal colonization. As we described previously [21,23], rabbits were first administered with famotidine (0.75 mg per kg body weight) given intravenously (IV) at the ear vein 3 h before inoculation. Just before inoculation, rabbits were sedated with dexmedetomidine (0.1 mg per kg body weight) given intramuscularly and then anesthetized with the inhalation of 5% isoflurane, followed by inoculation with 3 mL 5% sodium bicarbonate, 5 × 10 10 CFU ETEC strain JF2101 (in 5 mL), and finally 3 mL 5% sodium bicarbonate.…”

“…If adhesin MEFA-II could be further improved to enhance functional anti-STa immunity and also induce neutralizing antibodies against the other ETEC toxin (LT), this protein antigen can be potentially combined with MEFA CFA/I/II/IV, another polyvalent adhesin antigen previously constructed to target seven different ETEC adhesins, for an ETEC vaccine candidate. CFA/I/II/IV MEFA protein was demonstrated to induce functional antibodies against any of the seven most important ETEC adhesins (CFA/I and CS1-CS6) but also prevented intestinal colonization with ETEC bacteria [18][19][20][21]. Such a vaccine would synergistically protect against twelve ETEC adhesins and both toxins.…”

Mycosynthesis of CuO Nanoparticles Using Aspergillus niger and Their Bioefficiency against Human Pathogens

“…In turn, most E. coli bacterial cells exhibit commensalism in the small intestine, where the live facultative anaerobically. However, they can provoke a wide variety of diseases, such as sepsis, neonatal meningitis, diarrheal illness, central nervous system diseases, enteritis, and urinary tract diseases in healthy individuals [77]. Importantly, E. coli is a common cause of traveler's diarrhea and a prominent cause of pediatric diarrhea in developing countries [78].…”

Feasibility of avian antibodies as prophylaxis against enterotoxigenic escherichia coli colonization

“…The quest for broadly effective anti-ETEC vaccines long focused on identification and antigenicity of the myriad adhesin molecules expressed by various clinically important ETEC strains; however, this approach is vulnerable to antigenic drift and emergence of molecularly distinct CFs and CSs ( 5 ). A broader mechanistic approach has seen the emergence of multivalent protein-based ETEC vaccine candidates that induce antibodies neutralizing both LT and STa toxins as well as antibodies inhibiting adherence of multiple ETEC adhesins, which have been shown to be protective against ETEC toxin-mediated diarrhea in a pig challenge model ( 6 ). Further, such multivalent vaccines reduced colonization by the most virulent ETEC strain, H10407, in a rabbit intestinal colonization model ( 6 ).…”

“…A broader mechanistic approach has seen the emergence of multivalent protein-based ETEC vaccine candidates that induce antibodies neutralizing both LT and STa toxins as well as antibodies inhibiting adherence of multiple ETEC adhesins, which have been shown to be protective against ETEC toxin-mediated diarrhea in a pig challenge model ( 6 ). Further, such multivalent vaccines reduced colonization by the most virulent ETEC strain, H10407, in a rabbit intestinal colonization model ( 6 ). Despite these recent advances, however, no licensed vaccine against ETEC is available, though several are in early-stage clinical trials ( 7 , 8 ).…”