SAFETY AND IMMUNOGENICITY OF A NEXT GENERATION PURIFIED VERO RABIES VACCINE AS A SIMULATED INTRADERMAL POST-EXPOSURE PROPHYLAXIS IN ADULTS AND CHILDREN IN THAILAND: A PHASE 3, RANDOMIZED STUDY

Abstract

The aim of this Phase 3, randomized study was to assess the immunogenicity and safety of a purified Vero cell rabies vaccine, PVRV-NG2, compared with the current rabies standard of care vaccine (PVRV), using a simulated post-exposure prophylaxis regimen with intradermal (ID) vaccination on day (D) 0, D3, D7, and D28 in healthy pediatric (≥1 to <18 years of age) and adult (≥18 years of age) participants, with concomitant administration of rabies immunoglobulin [RIG]).  Rabies virus neutralizing antibody (RVNA) titers were determined on D0, D14, D42, and D90.  Enrolled participants (n = 402) consisted of pediatrics (n = 168) divided into two groups, Group 1 receiving PVRV-NG2 (n = 112) and Group 2 receiving PVRV (n = 56), and of adults (n = 234) divided into 4 groups, Group 3 receiving PVRV-NG2+equine RIG (ERIG, n = 26), Group 4 receiving PVRV+ERIG (n = 14), Group 5 receiving PVRV-NG2+human RIG (HRIG, n = 129), and Group 6 receiving PVRV+HRIG (n = 65).  By D14, nearly all pediatric participants achieved RVNA titer ≥0.5 IU/ml, while only 52-75% of adults achieved this titer when both vaccines were co-administered with RIGs.  By D42, 96 and 100% of adults who received PVRV-NG2 and PVRV respectively, had RVNA titers ≥0.5 IU/ml.  By D90, all, except two, pediatric participants had RVNA titers that persisted at ≥0.5 IU/ml, while 75 and 78% of adults who received PVRV-NG2 and PVRV respectively, had maintained this titer.  No safety concerns were identified, and safety profiles were similar across groups.  Overall, the immunogenicity and safety profiles of PVRV-NG2 when administered alone or co-administered with HRIG were comparable with those of PVRV, supporting the application of intradermal administration for post-exposure vaccination using the updated Thai Red Cross vaccination schedule (Clinicaltrials.gov no: NCT04478084).