Factors influencing rabies vaccines immunogenicity during post-exposure prophylaxis: a systematic literature search...

Rabies post-exposure prophylaxis (PEP) requires timely appropriate wound management and vaccination (including concomitant rabies immunoglobulin [RIG], depending on vaccination history and wound severity) to ensure rapid increases in rabies virus neutralizing antibody (RVNA) titers, a surrogate marker of protection. In this systematic review and meta-analysis, we assessed factors influencing the immunogenicity of rabies vaccines administered as PEP.

PubMed, Embase, and The Cochrane Library were systematically searched for randomized controlled trials published in English, French, Spanish, or Portuguese from January 1, 1983 to March 28, 2022 reporting the immunogenicity of rabies vaccines, specifically rabies human diploid cell vaccine (Imovax Rabies), purified Vero cell rabies vaccine (Verorab), and purified chick embryo cell rabies vaccine (RabAvert/Rabipur), as part of PEP in healthy individuals. Pooled RVNA geometric mean titers (GMTs) and seroconversion rates at Day 14 (D14) post-vaccination, determined by rapid fluorescent focus inhibition test, were estimated using random effects meta-analyses.

We identified 1040 studies, of which 67 (9689 participants across 140 intervention groups) were included. The pooled RVNA GMT across all vaccines at D14 post-vaccination was 8.19 (95% CI: 6.73-9.98) and did not differ significantly by vaccine, administration route, or RIG use; however, there were significant interlaboratory differences. Meta-regression analysis, including titration year, demonstrated a negative association with log-transformed RVNA GMTs, equating to a 4.18% reduction (95% CI: -5.89 to -2.44) in log-transformed GMTs per year during the period assessed. Across all vaccines assessed, the pooled seroconversion rate by D14 post-vaccination was 98% (95% CI: 97-98; n = 7023; I² = 64%) and was not impacted by vaccine, administration route, RIG use, test laboratory, or titration year.

Although RVNA GMTs appear to have decreased by titration year, there was no clinically meaningful impact on immunogenicity, and the three licensed rabies vaccines assessed are expected to provide similar protection.