Factors influencing the immune response after a single-dose 3-visit pre-exposure rabies intradermal vaccination schedule: a retrospective multivariate analysis

Background: The World Health Organization (WHO) recommends intradermal (ID) rabies vaccination as a safe and immunogenic alternative to intramuscular administration. The aim of this study is to determine which factors influence the levels of rabies virus neutralizing antibodies (RVNA) after a 3-visit ID rabies vaccination.

Methods: This is a retrospective secondary data analysis study based on electronic health record vaccination data of Belgian military subjects who received ID rabies Pre-exposure prophylaxis (PrEP) with a single-dose 3-visit regimen during the period 2014-2017. Logistic regression was performed to identify predictive factors of RVNA level >= 3.0 IU/mL and >10 IU/mL.

Results: The second analysis performed on the 2025 subjects (100% seroconverted with a RVNA >= 0.5 IU/mL) shows a significantly better immune response in subjects younger than 30 years compared to all other age-groups, a gender-difference to predict RVNA >= 3.0 IU/mL (OR 2.30 [1.26-4.22] comparing "female" to "male") and the influence of the vaccination schedule (OR 2.28 [1.15-4.53] comparing "late - very variable" to "correct" schedule) to predict > 10 IU/ml. Multivariate analysis also demonstrates that a postponed serology control significantly influences the Rapid Fluorescent Focus Inhibition Test (RFFIT).

Conclusion: Gender and age significantly influence the response to ID rabies vaccine. Timing of RVNA determination is important to correctly assess the response to vaccination. A single-dose 3-visit ID rabies PrEP schedule is a dose-sparing effective alternative to the double-dose 2-visit ID schedule. When the minimum time interval between doses is respected, RVNA determination is not necessary.