Efficacy of whole-cell pneumococcal vaccine in mice: A systematic review and meta-analysis.

BACKGROUND: Despite the fact that pneumococcal conjugate vaccines (PCVs) have significantly reduced the rate of invasive pneumococcal diseases through the use of vaccine serotypes, infection with Streptococcus pneumoniae remains a major public health hazard. Serotype-independent vaccines that are economically viable species of common protein antigens such as whole-cell vaccines (WCVs) are needed. Considering the ongoing debate about the effectiveness of WCVs, a systematic literature review and meta-analysis was carried out to determine the efficacy of WCVs against colonization in mice.

MATERIAL AND METHODS: A systematic review was undertaken of published studies on the protection (colonized/uncolonized) of whole cell pneumococcal vaccine in mice. The search terms used were "whole cell vaccine" and "Streptococcus pneumoniae" in PubMed, Google Scholar, Embase, Web of Science and Scopus engines. Data was extracted from original publications and a meta-analysis was performed on studies divided into sub-groups by the number of inoculations, type of sample, type of adjuvant, time of sampling, design of study and quality of study.

RESULTS: Ten eligible articles published from 2000 to 2016 were included in this review. The meta-analysis was performed on eight out of 10 studies and demonstrated that the estimated pooled risk ratios (RRs) for comparison of colonization between the vaccinated and unvaccinated mice for outcomes 1 and 2 were 0.18 and 0.24, respectively. Lower RRs were observed in sub-groups that were inoculated with vaccines three times, those using cholera toxin (CT) adjuvants and those obtained as tracheal specimens from the mice.

CONCLUSIONS: The best protocol for use of a WCV is its application with CT adjuvant administered intranasally in three inoculations at doses of 10⁸ CFU. Further studies performed under similar conditions to obtain accurate results on the effectiveness of this vaccine are recommended.