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, F. (*IGUAL CONTRIBUCIÓN); B. MARELLI (*IGUAL CONTRIBUCIÓN); GOLDBAUM F; MUÑOZ L; ETCHEVERS L; SILVESTRINI P; NOTARO U.S; SALVETTI, N; ZYLBERMAN V; ORTEGA H

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias 2022, LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2022

The urgency of COVID-19 treatments precluded traditionaldrug discovery pathways, given their long times,highlighting the need for suitable tools to accelerate theprocess. In this study, preclinical biodistribution and safetyof an antibody-based treatment were assessed undergood laboratory practices with the aim of validating anin vivo bioimaging approach as a tool for improve drugstudies. CoviFab (INM005), F(ab′)2 fragment derivedfrom equine polyclonal antibodies labeled with IRDye®800CW, was administered intravenously at a dose of 4mg/kg in male BALB/cCmedc mice, 6-7 weeks old, 21+/-1.5 g at 0 and 48h. Mice were imaged in vivo at differenttimes after injections with the Pearl® Trilogy ImagerLICOR imaging system in the near infrared (NIR). At 96and 144h, mice (n=6) were sacrificed for ex vivo imagingand hematological, serum, pathological and histopathologicalanalyses. CoviFab was rapidly localized in vivoin all regions analyzed. In liver and ears (metabolizationand distribution, respectively), fluorescence was higherthan basal throughout the study. In kidney and bladder, itwas clearly visualized 24h after each injection. No toxicologicalor macroscopic changes were observed in the animals.Relative organ weights were similar in treated andcontrol animals. The ex vivo study supports the in vivobiodistribution data, confirming that CoviFab remains incirculation for more than 144h after the first administration(96h after the second), consistent with that describedfor others mono and polyclonal antibodies. Therefore,fluorescence in the lungs demonstrates the arrival ofthe drug at the target organ of the virus. CoviFab wasconsidered safe, with no observable adverse effects andin vivo and ex vivo results demonstrate its localizationand permanence in organs of interest for COVID-19. Inagreement with previous studies, these results reaffirmthat in vivo bioimaging studies could be strong predictorsof biodistribution during the drug development.