Protective efficacy of combined monoclonal antibody docaravimab and miromavimab preparation against classical rabies virus: A preclinical study in BALB/c mice

INTRODUCTION. Medicinal products based on monoclonal antibodies (mAbs) is one of the promising options for post-exposure rabies prophylaxis. Since Russian pharmaceutical market does not offer anti-rabies mAbs, a combined docaravimab and miromavimab preparation requires a preclinical study of its protective properties against street strains of the rabies virus circulating in the Russian Federation. In this regard, the need to conduct experimental studies is urgent in order to substantiate the efficacy of such products.

AIM. This study aimed to investigate protective efficacy of the combined anti-rabies mAb preparation of docaravimab and miromavimab against the classical rabies virus in BALB/c mice.

MATERIALS AND METHODS. A combination of anti-rabies mAbs, docaravimab and miroma-­vimab, was used as a test drug, while anti-rabies immunoglobulin Rebinolin served as a comparator drug. Street rabies virus strains were used: 777-M, Russia/Samara/2018, RABV/Russia/SP48SolMak/2020, and fixed CVS strain. In the efficacy study, 960 BALB/c mice (480 females, 480 males) were used, forming 23 groups of 20 animals each (10 males and 10 females). Mice groups 3–18 were intramuscularly infected with the rabies virus, and after 6 or 24 hours, either docaravimab and miromavimab combination or a comparator drug (Rebinolin) was administered intramuscularly. Mice from group 1 and 2 were injected with 0.9% sodium chloride solution (placebo). Mice from groups 19–22 served as a dose control for the virus; group 23 served as an intact control. To assess protective properties, mice were weighed; incubation and clinical period, average life span, and protection from clinical manifestations and death was determined. Virus infectivity was evaluated on BALB/c mice after their intracerebral infection. The specific cause of animal death was confirmed using real-time reverse transcriptase polymerase chain reaction.

RESULTS. A combined preparation based on anti-rabies mAbs docaravimab and miromavimab resulted in a significantly increased body weight, average life span, and protection from clinical rabies manifestations in infected mice compared with rabies virus dose control groups. The combined preparation demonstrated high protective efficacy against rabies virus strains, not inferior to that of the comparator. Administration of the combined preparation to mice 6 hours after infection (strains 777-M, Russia/Samara/2018, RABV/Russia/SP48SolMak/2020, CVS) showed 90–100% protection of male and female mice against death; after 24 hours — 90–100% of male and 96–100% of female mice.

CONCLUSIONS. An experiment in mice shows high protective efficacy of a combined docaravimab and miromavimab preparation against street strains of the classic rabies virus relevant to the Russian Federation. Protective efficacy of the combined preparation is not inferior to the comparator, thus warranting further preclinical and clinical studies.

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