Evidence-Based Approaches for Determining Effective Target Antigens to Develop Vaccines against Post-Weaning Diarrhea Caused by Enterotoxigenic Escherichia coli in Pigs: A Systematic Review and Network Meta-Analysis

SIMPLE SUMMARY: Owing to the levels of mortality and morbidity associated with enterotoxigenic Escherichia coli (ETEC) inflicted diarrhea, as well as the scope of the global disease burden, several initiatives to develop effective vaccines have been launched. We conducted a meta-analysis to assess the efficacy of commercially available and candidate vaccines against ETEC-associated post-weaning diarrhea in pigs. The effectiveness of vaccines was evaluated using three clinical outcomes: mortality, diarrhea, and average daily weight gain. Subsequently, a simultaneous comparison of vaccines was conducted using a Bayesian network meta-analysis approach to generate evidence-based data on the most effective vaccine based on their target antigens. The results indicated that vaccinated pigs had a significantly lower risk of diarrhea and mortality when compared to non-vaccinated pigs. Furthermore, the findings also showed that a multivalent vaccine that targets both fimbriae and enterotoxins should be prioritized to combat post-weaning diarrhea in pigs. ABSTRACT: In this study, we conducted a meta-analysis (MA) and systematic review to evaluate the effectiveness of vaccines against post-weaning diarrhea (PWD), caused by enterotoxigenic Escherichia coli (ETEC), in piglets. A Bayesian network meta-analysis (NMA) was also performed to compare the effects of combining different target antigens on vaccine efficacy. Relevant electronic databases were searched using pre-specified search terms, and 17 studies were selected based on three outcomes: diarrhea, mortality, and average daily weight gain (ADWG). In pairwise MA, the vaccinated group showed a significant decrease in diarrhea (OR = 0.124 [0.056, 0.275]) and mortality (OR = 0.273 [0.165, 0.451]), and a significant increase in ADWG (SMD = 0.699 [0.107, 1.290]) compared with those in controls. Furthermore, NMA results showed that all vaccine groups, except for group D (LT enterotoxin), were effective against PWD. Rank probabilities indicated that the F4 + F18 + LT combination was the best regimen for preventing diarrhea (SUCRA score = 0.92) and mortality (SUCRA score = 0.89). NMA also demonstrated that, among the vaccine groups, those inducing simultaneous anti-adhesion and antitoxin immunity had the highest efficacy. Our results provide evidence-based information on the efficacy of vaccines in reducing PWD incidence in pigs and may serve as guidelines for antigen selection for commercial vaccine development in the future.