BACKGROUND: In a randomized controlled study (NCT01622062) a 1-week, 4-site intradermal (ID, 4-4-4-0-0) post-exposure prophylaxis (PEP) rabies vaccination regimen with purified Vero cell rabies vaccine (PVRV, Verorab®, Sanofi Pasteur), either without (Group 1) or with (Group 2) purified equine rabies immunoglobulin (ERIG), patients in the Philippines achieved seroconversion rates at Day 14 that were non-inferior to that of the updated Thai Red Cross (TRC) 28-day, 2-site (2-2-2-0-2) ID regimen with ERIG (Group 3). Presented here are the annual immunogenicity data up to five years after the last primary dose, and the immunogenicity and safety data following simulated PEP with single-visit, 4-site ID regimen. METHODS:Rabies virus neutralizing antibodies (RVNA) were determined by rapid fluorescent focus inhibition test (RFFIT). Participants (n = 397) received simulated PEP vaccination ID at Year 5 and RVNAs were assessed at Day 11 post-vaccination. RESULTS:Seroconversion rates (RVNA titres ≥ 0.5 IU/mL) during annual follow-up remained >95% in Group 1 and were relatively stable at 80-90% in Group 2, but decreased from 80% to 64% in Group 3. RVNAgeometric mean titres (GMTs) in Group 1 were consistently higher than in the other two groups, and those in Group 3 were generally lower than in the other two groups. There was a clear anamnestic response to vaccination in all groups, with all participants achieving RVNA titres ≥ 0.5 IU/mL at Day 11 post-simulated PEP booster vaccination. There were no safety concerns raised during annual follow-up and with simulated post-exposure vaccination with PVRV. CONCLUSION: The shortened, 1-week, 4-site ID regimen with PVRV achieved persistently higher RVNA titres than the updated 2-site TRC regimen, and more participants remained seroprotected up to five years after the last dose of primary immunization. Simulated post-exposure with 4-site ID rapidly induced an anamnestic response indicative of robust protection.
RCT Entities:
BACKGROUND: In a randomized controlled study (NCT01622062) a 1-week, 4-site intradermal (ID, 4-4-4-0-0) post-exposure prophylaxis (PEP) rabies vaccination regimen with purified Vero cell rabies vaccine (PVRV, Verorab®, Sanofi Pasteur), either without (Group 1) or with (Group 2) purified equine rabies immunoglobulin (ERIG), patients in the Philippines achieved seroconversion rates at Day 14 that were non-inferior to that of the updated Thai Red Cross (TRC) 28-day, 2-site (2-2-2-0-2) ID regimen with ERIG (Group 3). Presented here are the annual immunogenicity data up to five years after the last primary dose, and the immunogenicity and safety data following simulated PEP with single-visit, 4-site ID regimen. METHODS: Rabies virus neutralizing antibodies (RVNA) were determined by rapid fluorescent focus inhibition test (RFFIT). Participants (n = 397) received simulated PEP vaccination ID at Year 5 and RVNAs were assessed at Day 11 post-vaccination. RESULTS: Seroconversion rates (RVNA titres ≥ 0.5 IU/mL) during annual follow-up remained >95% in Group 1 and were relatively stable at 80-90% in Group 2, but decreased from 80% to 64% in Group 3. RVNA geometric mean titres (GMTs) in Group 1 were consistently higher than in the other two groups, and those in Group 3 were generally lower than in the other two groups. There was a clear anamnestic response to vaccination in all groups, with all participants achieving RVNA titres ≥ 0.5 IU/mL at Day 11 post-simulated PEP booster vaccination. There were no safety concerns raised during annual follow-up and with simulated post-exposure vaccination with PVRV. CONCLUSION: The shortened, 1-week, 4-site ID regimen with PVRV achieved persistently higher RVNA titres than the updated 2-site TRC regimen, and more participants remained seroprotected up to five years after the last dose of primary immunization. Simulated post-exposure with 4-site ID rapidly induced an anamnestic response indicative of robust protection.
Authors: Patrick Soentjens; Nicole Berens-Riha; Yven Van Herrewege; Pierre Van Damme; Emmanuel Bottieau; Raffaella Ravinetto Journal: BMJ Glob Health Date: 2021-02