Factors influencing the immune response after a double-dose 2-visit pre-exposure rabies intradermal vaccination schedule: A retrospective study

Background: Double-dose 2-visit intradermal rabies schedules (2²ID) have recently been accepted by the World Health Organization (WHO) as Pre-Exposure Prophylaxis (PrEP). The aim of this study is to determine which factors influence the levels of rabies virus neutralizing antibodies (RVNA) after a 2²ID rabies vaccination schedule. Methods: This is a retrospective study based on electronic health record vaccination data of subjects from the Belgian Armed Forces who received the 2²ID rabies PrEP. An antibody titer ≥0.5 IU/mL, measured by rapid fluorescent focus inhibition test, is defined by the WHO as an adequate immune response after PrEP. Logistic regression was performed in order to identify predictive factors of RVNA level ≥3.0 IU/ml and >10 IU/ml. Results: 301 subjects were included. 297 (98,6%) seroconverted with a RVNA ≥ 0.5 IU/ml. Multivariate analysis shows a significant better immune response in the subjects where the second dose was administered later on than on day 7 (RVNA >10 IU/ml (OR: 3.01 [1.36–6.67])). Postponing the timing of the serology control also influenced significantly the rapid fluorescent focus inhibition test (RVNA ≥ 3.0 IU/ml (OR: 0.12 [0.06–0.24]) and RVNA > 10 IU/ml (OR: 0.14 [0.06–0.29])). Conclusion: A 2²ID rabies PrEP vaccination schedule is highly effective and provides an adequate immune response in most subjects in a real live setting. Timing of the second vaccine dose significantly influences the response to ID rabies vaccine. Timing of RVNA determination is important in order to correctly assess the response to vaccination.