Do Rotavirus Strains Affect Vaccine Effectiveness? A Systematic Review and Meta-analysis

Abstract

Background: Rotavirus causes 215,000 deaths from severe childhood diarrhea annually. Concerns exist that a monovalent vaccine (RV1) and a pentavalent vaccine (RV5) may be less effective against rotavirus strains not contained in the vaccines. We estimated the vaccine effectiveness (VE) of RV1 and RV5 against severe rotavirus gastroenteritis caused by vaccine (homotypic) and nonvaccine (partially and fully heterotypic) strains.

Methods: After conducting a systematic review, we meta-analyzed 31 case-control studies (N = 27,293) conducted between 2006 and 2020 using a random-effects regression model.

Results: In high-income countries, RV1 VE was 10% lower against partially heterotypic (P = 0.04) and fully heterotypic (P = 0.10) compared with homotypic strains (homotypic VE: 90% [95% confidence intervals (CI): 82-94]; partially heterotypic VE: 79% [95% CI: 71-85]; fully heterotypic VE: 80% [95% CI: 65-88]). In middle-income countries, RV1 VE was 14-16% lower against partially heterotypic (P = 0.06) and fully heterotypic (P = 0.04) compared with homotypic strains (homotypic VE: 81% [95% CI: 69-88]; partially heterotypic VE: 67% [95% CI: 54-76]; fully heterotypic VE: 65% [95% CI: 51-75]). Strain-specific RV5 VE differences were less pronounced, and primarily derived from high-income countries. Limited data were available from low-income countries.

Conclusions: Vaccine effectiveness of RV1 and RV5 was somewhat lower against nonvaccine than vaccine strains. Ongoing surveillance is important to continue long-term monitoring for strain replacement, particularly in low-income settings where data are limited.

FIGURE 1.

Study selection.

FIGURE 2.

A: Vaccine effectiveness by country income level and strain type for RV1. The 95% confidence intervals may differ slightly from original publications due to small differences in back-calculation of odds ratios from abstracted vaccine effectiveness estimates or truncation of lower limits at 0 (REF Ali 2016). B: Vaccine effectiveness by country income level and strain type for RV5. NS indicates not specified, i.e., raw numbers not specified in the paper.