Immunogenicity after pre- and post-exposure rabies vaccination: A systematic review and dose-response meta-analysis

Background: There are a myriad of vaccine schedules for rabies pre- (PrEP) and post-exposure prophylaxis (PEP) that differ in the number and time doses, number of visits, length of schedule, and route of administration. The objective of this study was to systematically review the evidence and investigate how the differences in schedules influence titres over time.

Methods: Four databases were searched from inception to January 2020 for rabies PrEP and PEP studies. A dose–response meta-analysis was utilised to pool geometric mean titres (GMT) over time. Subgroup analyses by route of administration, age group, and schedule were conducted.

Results: 80 studies met the inclusion criteria and contributed with 191 datasets and 12,413 participants. Both intradermal (ID) and intramuscular (IM) PrEP/PEP produce adequate GMTs. Significantly lower GMT levels were achieved in older (>50yrs) compared to younger (<50yrs) participants. Short 1-week schedules were as effective as longer schedules that can take between 3 and 12 weeks to complete.

Conclusions: Several effective ID and IM schedules were identified, the selection of a schedule should take into account the patient’s needs, costs, availability to return for subsequent doses, and the time required to complete the schedule. Older individuals warrant special attention as they develop lower antibody response.