Repeat-dose and local tolerance toxicity of SARS-CoV-2 FINLAY-FR-02 vaccine candidate in Sprague Dawley rats

Reynaldo Oliva-Hernández; Mildrey Fariñas-Medina; Tamara Hernández-Salazar; Ambar Oyarzabal-Vera; Juan F Infante-Bourzac; Sandra Rodríguez-Salgueiro; Laura M Rodríguez-Noda; Yisabel Arranguren-Masorra; Yanet Climent-Ruíz; Sonsire Fernández-Castillo; Daniel G-Rivera; Darielys Santana-Mederos; Belinda Sánchez-Ramírez; Dagmar García-Rivera; Yury Valdés-Barbín; Vicente Vérez-Bencomo

doi:10.1016/j.tox.2022.153161

Repeat-dose and local tolerance toxicity of SARS-CoV-2 FINLAY-FR-02 vaccine candidate in Sprague Dawley rats

Toxicology. 2022 Apr 15:471:153161. doi: 10.1016/j.tox.2022.153161. Epub 2022 Mar 29.

Authors

Reynaldo Oliva-Hernández¹, Mildrey Fariñas-Medina², Tamara Hernández-Salazar³, Ambar Oyarzabal-Vera⁴, Juan F Infante-Bourzac⁵, Sandra Rodríguez-Salgueiro⁶, Laura M Rodríguez-Noda⁷, Yisabel Arranguren-Masorra⁸, Yanet Climent-Ruíz⁹, Sonsire Fernández-Castillo¹⁰, Daniel G-Rivera¹¹, Darielys Santana-Mederos¹², Belinda Sánchez-Ramírez¹³, Dagmar García-Rivera¹⁴, Yury Valdés-Barbín¹⁵, Vicente Vérez-Bencomo¹⁶

Affiliations

¹ Finlay Institute of Vaccine, 198 and 17th Street, Havana 11600, Cuba. Electronic address: roh@finlay.edu.cu.
² Finlay Institute of Vaccine, 198 and 17th Street, Havana 11600, Cuba. Electronic address: mfarinas@finlay.edu.cu.
³ Finlay Institute of Vaccine, 198 and 17th Street, Havana 11600, Cuba. Electronic address: thernandez@finlay.edu.cu.
⁴ Natural Products Center, 198 e/ 19th and 21th Street, Havana 11600, Cuba. Electronic address: ambar.oyarzabal@cnic.cu.
⁵ Finlay Institute of Vaccine, 198 and 17th Street, Havana 11600, Cuba. Electronic address: jinfante@finlay.edu.cu.
⁶ Natural Products Center, 198 e/ 19th and 21th Street, Havana 11600, Cuba. Electronic address: sandra.rodriguez@cnic.cu.
⁷ Finlay Institute of Vaccine, 198 and 17th Street, Havana 11600, Cuba. Electronic address: lmrodriguez@finlay.edu.cu.
⁸ Finlay Institute of Vaccine, 198 and 17th Street, Havana 11600, Cuba. Electronic address: yaranguren@finlay.edu.cu.
⁹ Finlay Institute of Vaccine, 198 and 17th Street, Havana 11600, Cuba. Electronic address: ycliment@finlay.edu.cu.
¹⁰ Finlay Institute of Vaccine, 198 and 17th Street, Havana 11600, Cuba. Electronic address: sfernandez@finlay.edu.cu.
¹¹ Laboratory of Synthetic and Biomolecular Chemistry, Faculty of Chemistry, University of Havana, Zapata & G, Havana 10400, Cuba. Electronic address: dgrivera78@gmail.com.
¹² Finlay Institute of Vaccine, 198 and 17th Street, Havana 11600, Cuba. Electronic address: dsantana@finlay.edu.cu.
¹³ Center of Molecular Immunology, P.O. Box 16040, 216 street and 15th Avenue, Havana, Cuba. Electronic address: belinda@cim.sld.cu.
¹⁴ Finlay Institute of Vaccine, 198 and 17th Street, Havana 11600, Cuba. Electronic address: dagarcia@finlay.edu.cu.
¹⁵ Finlay Institute of Vaccine, 198 and 17th Street, Havana 11600, Cuba. Electronic address: yvaldes@finlay.edu.cu.
¹⁶ Finlay Institute of Vaccine, 198 and 17th Street, Havana 11600, Cuba. Electronic address: vicente.verez@finlay.edu.cu.

Abstract

This study evaluates safety of FINLAY-FR-02, a vaccine candidate against SARS-CoV-2 based on the recombinant receptor binding domain conjugated to tetanus toxoid, in a preclinical, repeat-dose toxicity and local tolerance study. Sprague Dawley rats were randomly allocated to three experimental groups: control (receiving physiological saline solution); placebo (receiving all vaccine components except antigens) and vaccine group (receiving three doses of the vaccine candidate, 37.5 µg of RBD) administered intramuscularly in hind limbs at 24 h intervals during three days. We evaluated physiological condition, pain, food and water consumption, body temperature, dermal irritability, injection site temperature and inﬂammation, immunological response, blood chemistry, relative organ weight, histopathology and immunotoxicology. The product was well tolerated; no clinically relevant changes, pain, local effects or adverse systemic toxicological changes or deaths were observed. These preliminary results permitted the Cuban regulatory authorities to authorize clinical trials in humans.

Keywords: COVID-19 vaccine; Conjugate vaccine; Cuba; Local tolerance; RBD; Repeat-dose toxicity; SARS-CoV-2; Sprague Dawley rats; Tetanus toxoid.