Safety and operational feasibility of single versus cocktail rabies monoclonal antibodies for post-exposure prophylaxis in a resource-limited setting

BACKGROUND: Rabies is almost universally fatal once symptoms develop but is preventable through timely post-exposure prophylaxis (PEP). Global shortages of human and equine rabies immunoglobulin (RIG) have led the World Health Organization to recommend human monoclonal antibodies (mAbs) as acceptable alternatives. Comparative real-world data on single-antibody versus two-antibody cocktail mAbs are limited, particularly from endemic, resource-limited settings. METHODS: A comparative observational study was conducted in a high-volume rabies PEP clinic in India between October 2021 and December 2022. Consecutive patients with category III animal exposures received either a single human anti-rabies mAb (Rabishield; n = 159) or a two-mAb cocktail (Twinrab; n = 159) in combination with WHO-recommended vaccine. Primary outcomes included safety, ease of administration, and operational feasibility. Data were analysed using independent t-tests and chi-square or Fisher's exact tests, with p < 0.05 considered significant. RESULTS: Mean age was 29.7 ± 19.4 years in the Rabishield group and 32.8 ± 20.4 years in the Twinrab group. Ease of infiltration was rated "easy" in 66.7% versus 62.9% of patients (p = 0.63). Local adverse events were uncommon, with pain reported in 2.5% versus 7.5% (p = 0.07) and erythema in ≤ 1.3% of participants. No serious systemic adverse events occurred. Rabishield required more vials per patient (2.28 ± 0.84 vs 2.00 ± 0.69; p = 0.001) and had a higher mean infiltration volume (4.7 ± 1.9 mL vs 4.0 ± 1.6 mL; p < 0.001), while wastage was similar between groups (1.03 ± 0.72 mL vs 1.03 ± 0.69 mL; p = 0.95). CONCLUSIONS: Both single and cocktail human anti-rabies mAbs were safe, well tolerated, and operationally feasible in a programmatic setting. The slightly higher volume and vial requirement for Rabishield may have cost and logistics implications. These findings support broader mAb adoption to address RIG shortages in rabies-endemic, resource-limited settings.