Rabies immunoglobulin human 500unit solution for injection vials

BackgroundRabies post-exposure prophylaxis (PEP) requires timely appropriate wound management and vaccination (including concomitant rabies immunoglobulin [RIG], depending on vaccination history and wound severity) to ensure rapid increases in rabies virus neutralizing antibody (RVNA) titers, a surrogate marker of protection. In this systematic review and meta-analysis, we assessed factors influencing the immunogenicity of rabies vaccines administered as PEP.MethodsPubMed, Embase, and The Cochrane Library were systematically searched for randomized controlled trials published in English, French, Spanish, or Portuguese from January 1, 1983 to March 28, 2022 reporting the immunogenicity of rabies vaccines, specifically rabies human diploid cell vaccine (Imovax Rabies), purified Vero cell rabies vaccine (Verorab), and purified chick embryo cell rabies vaccine (RabAvert/Rabipur), as part of PEP in healthy individuals. Pooled RVNA geometric mean titers (GMTs) and seroconversion rates at Day 14 (D14) post-vaccination, determined by rapid fluorescent focus inhibition test, were estimated using random effects meta-analyses.ResultsWe identified 1040 studies, of which 67 (9689 participants across 140 intervention groups) were included. The pooled RVNA GMT across all vaccines at D14 post-vaccination was 8.19 (95% CI: 6.73-9.98) and did not differ significantly by vaccine, administration route, or RIG use; however, there were significant interlaboratory differences. Meta-regression analysis, including titration year, demonstrated a negative association with log-transformed RVNA GMTs, equating to a 4.18% reduction (95% CI: -5.89 to -2.44) in log-transformed GMTs per year during the period assessed. Across all vaccines assessed, the pooled seroconversion rate by D14 post-vaccination was 98% (95% CI: 97-98; n = 7023; I2 = 64%) and was not impacted by vaccine, administration route, RIG use, test laboratory, or titration year.ConclusionsAlthough RVNA GMTs appear to have decreased by titration year, there was no clinically meaningful impact on immunogenicity, and the three licensed rabies vaccines assessed are expected to provide similar protection.

Abstract licence: CC BY

Abstract Background A serum-free, highly purified Vero rabies vaccine–next generation (PVRV-NG2) is under development. We conducted a phase III trial to describe the safety and immunogenicity profile of PVRV-NG2 compared with those of licensed purified Vero rabies vaccine (PVRV) in a simulated rabies postexposure prophylaxis (PEP) Zagreb regimen in Thailand. Methods Healthy adults aged ≥18 years (n = 201) were randomized in a 2:1 ratio to receive PVRV-NG2 or PVRV in a rabies PEP Zagreb (days 0, 7, 21 [2-1-1]) regimen, with concomitant human rabies immunoglobulin (HRIG) at day 0. Immunogenicity end points included the proportion of participants with rabies virus–neutralizing antibody (RVNA) titers ≥0.5 IU/mL at days 0, 14, and 35. Safety outcomes were also assessed. Results A total of 199 participants completed the study (PVRV-NG2 n = 133, PVRV n = 66). In the PVRV-NG2 group and PVRV group, respectively, 91.0% (95% CI, 84.1%–95.6%) and 94.6% (95% CI, 85.1%–98.9%) had RVNA titers ≥0.5 IU/mL at day 14, increasing to 100% (95% CI, 96.8%–100%) and 100% (95% CI, 93.5%–100%) by day 35. The vaccines had similar safety profiles, and there were no safety concerns. Conclusions PVRV-NG2 showed acceptable safety and immunogenicity profiles when co-administered with HRIG in a simulated PEP Zagreb regimen in healthy adults in Thailand.

Abstract licence: CC BY 4.0

What is already known about this topic?Anti-rabies monoclonal antibodies in combination with rabies vaccines have demonstrated safety and immunogenicity as alternatives to rabies immunoglobulins for category III post-exposure prophylaxis in adults.What is added by this report?This randomized, double-blind, active-control phase III trial demonstrates the immunogenicity and safety of an anti-rabies monoclonal antibodies in individuals aged What are the implications for public health practice?These findings support the use of recombinant human monoclonal antibodies in pediatric populations and their potential role as alternative passive immunization options for category III rabies post-exposure prophylaxis in individuals aged <18 years.

Abstract licence: CC BY