IMPORTANCE OF BIOIMAGING IN ASSESSING THE PRECLINICAL SAFETY AND IN VIVO BIODISTRIBUTION OF COVIFAB, AN RBD-SPECIFIC F(AB′)2 FRAGMENT DERIVED FROM EQUINE POLYCLONAL ANTIBODIES.

SALINAS, FACUNDO J.; MARELLI, BELKIS; SANGUINETI, SANTIAGO; GOLDBAUM, FERNANDO; MUÑOZ, LUCIANA; ETCHEVERS, LUCAS; SILVESTRINI, PAULA; NOTARO, ULISES; SALVETTI, NATALIA R.; ZYLBERMAN, VANESA; ORTEGA, HUGO H.

Mar del Plata

Congreso; LXVII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2022

REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022

The urgency of COVID-19 treatments precluded traditional drug discovery pathways, given their long times, highlighting the need for suitable tools to accelerate the process. In this study, preclinical biodistribution and safety of an antibody-based treatment were assessed under good laboratory practices with the aim of validating an in vivo bioimaging approach as a tool for improve drug studies.CoviFab (INM005), F(ab′)2 fragment derived from equine polyclonal antibodies labeled with IRDye® 800CW, was administered intravenously at a dose of 4 mg/kg in male BALB/cCmedc mice, 6-7 weeks old, 21+/-1.5 g at 0 and 48h. Mice were imaged in vivo at different times after injections with the Pearl® Trilogy Imager LICOR imaging system in the near infrared (NIR). At 96 and 144h, mice (n=6) were sacrificed for ex vivo imaging and hematological, serum, pathological and histopathological analyses.CoviFab was rapidly localized in vivo in all regions analyzed. In liver and ears (metabolization and distribution, respectively), fluorescence was higher than basal throughout the study. In kidney and bladder, it was clearly visualized 24h after each injection. No toxicological or macroscopic changes were observed in the animals. Relative organ weights were similar in treated and control animals. The ex vivo study supports the in vivo biodistribution data, confirming that CoviFab remains in circulation for more than 144h after the first administration (96h after the second), consistent with that described for others mono and polyclonal antibodies. Therefore, fluorescence in the lungs demonstrates the arrival of the drug at the target organ of the virus.CoviFab was considered safe, with no observable adverse effects and in vivo and ex vivo results demonstrate its localization and permanence in organs of interest for COVID-19. In agreement with previous studies, these results reaffirm that in vivo bioimaging studies could be strong predictors of biodistribution during the drug development.