OBJECTIVES: To evaluate evidence from randomised controlled trials of the efficacy, safety, and immunogenicity of vaccines to prevent bubonic and/or pneumonic plague.
METHODS: A systematic literature review of RCTs was conducted of live or attenuated plague vaccines vs. placebo, no intervention or other plague vaccines. Medline, Embase and the Cochrane Library were searched from inception to 2020. Clinical trial registers, conference proceedings and bibliographies of relevant studies were also searched. Studies were screened by two independent researchers and risk of bias of included studies was assessed using the Cochrane Collaborations tool. Primary outcomes comprised efficacy (number of cases avoided by vaccination), safety (including adverse events) and immunologic outcomes (for example rise in antibody titres).
RESULTS: Of the 73 hits screened for inclusion, only 2 RCTs were identified. In total 300 participants were included across the RCTs, with follow-up times of 3 months and 13 months. Both trials were of reasonable quality. Given the heterogeneity between the trials in design, interventions and timepoints no quantitative synthesis for outcome data could be conducted. No data was available on the efficacy of either plague vaccine. The limited evidence for safety showed both vaccines were well tolerated with only mild to moderate adverse events. Similarly, both vaccines reported inducing immune responses.
CONCLUSIONS: Given the limited trials found in this systematic review, we are unable to conclude as to the efficacy, safety, and immunogenicity of vaccines to prevent plague. More trials of plague vaccines are needed with further evidence of their long-term effects.
