Interventions to improve oral vaccine performance in developing countries: a systematic review and meta-analysis

Background: Oral vaccines underperform in developing compared to developed countries. Whether interventions can improve oral vaccine performance remains uncertain. Methods: We did a systematic review and meta-analysis of interventions designed to increase oral vaccine efficacy or immunogenicity. Inclusion criteria for meta-analysis were ≥2 studies per intervention category and available seroconversion data. We conducted random-effects meta-analysis to determine summary relative risk (RR) estimates. The protocol is registered with PROSPERO (CRD42017060608). Findings: Of 2843 studies identified, 87 were eligible for qualitative synthesis and 66 for meta-analysis. Twenty-two different interventions were evaluated for oral poliovirus (OPV), rotavirus (RVV), cholera (OCV) and typhoid vaccines. There was generally high heterogeneity. Seroconversion to RVV was significantly increased by delaying the first RVV dose by four weeks (RR 1·37, 95%CI 1·16-1·62) and OPV seroconversion was increased with monovalent/bivalent-OPV compared to trivalent-OPV (RR 1·51, 95%CI 1·20-1·91). There was some evidence that separating RVV and OPV increased RVV seroconversion (RR 1·21, 95%CI 1·00-1·47) and that higher vaccine inoculum improved OCV seroconversion (RR 1·12, 95%CI 1·00-1·26). There was no evidence of effect for antihelminthics, antibiotics, probiotics, zinc, vitamin A, withholding breastfeeding, extra doses and vaccine buffering. Interpretation: Most strategies did not improve oral vaccine performance. Delaying RVV and reducing OPV valence were the only effective approaches identified and should be considered within immunisation programmes to reduce global enteric disease. New strategies to address the oral vaccine efficacy gap are urgently required. Funding: Wellcome Trust (201293/Z/16/Z and 108065/Z/15/Z); Bill and Melinda Gates Foundation; Medical Research Council; and WHO Polio Research Committee.Wellcome Trust (201293/Z/16/Z and 108065/Z/15/Z); Bill and Melinda Gates Foundation; Medical Research Council; and WHO Polio Research Committee