Comparative Long-Term Immunogenicity and Boosting of 3-Session Versus 4-Session Intradermal Rabies Post-Exposure Prophylaxis Regimens in Cambodia and Madagascar: The RESIST-3 Study

BACKGROUND: The abridged Institut Pasteur du Cambodge (IPC) 3-session intradermal (ID) rabies post-exposure prophylaxis (PEP) regimen has been shown to be as safe and immunogenic as the 4-session regimen previously recommended by WHO. This regimen reduces time, cost, improves adherence and access to PEP for underserved people. Our study aimed to compare long-term and anamnestic immune response after a rabies vaccine booster dose in people previously vaccinated with a 3 or 4-session ID PEP. METHODS: In this prospective, multi-site, comparative immunogenicity study, we measured rabies virus neutralizing antibody in 181 persons that had previously received 3- or 4-session ID PEP, 2, 5, or 10 years earlier in Cambodia or Madagascar, at day 0 and at day 7 after a booster. In addition, RABV-specific T cell response was evaluated in a sub-group of 35 Cambodian participants. RESULTS: All participants had rabies virus neutralizing antibody titers considered adequate (≥ 0.5 IU/mL) on day 7 after the booster dose. The overall geometric mean titer (GMT) of rabies antibody on day 0 and day 7 did not differ significantly between the 2 groups. Furthermore, RABV-specific T cell response was similar regardless of the ID PEP regimen initially received in a sub-group of 35 participants. CONCLUSIONS: In this multisite, real-world study, we showed that the 3-session ID PEP regimen provides robust long-term immunogenicity up to 10 years after initial PEP and ensures the induction of an adequate anamnestic response within 7 days after an additional booster in all participants.