Gamma-irradiated SARS-CoV-2 vaccine candidate, OZG-38.61.3, confers protection from SARS-CoV-2 challenge in human ACEII-transgenic mice

Turan, R. D.; Tastan, C.; Dilek Kancagi, D.; Yurtsever, B.; Sir Karakus, G.; Ozer, S.; Abanuz, S.; Cakirsoy, D.; Tumentemur, G.; Demir, S.; Seyis, U.; Kuzay, R.; Elek, M.; Ertop, G.; Arbak, S.; Acikel Elmas, M.; Hemsinlioglu, C.; Hatirnaz Ng, O.; Akyoney, S.; Sahin, I.; Kayhan, C. K.; Tokat, F.; Akpinar, G.; Kasap, M.; Kocagoz, A. S.; Ozbek, U.; Telci, D.; Sahin, F.; Yalcin, K.; Ratip, S.; Ince, U.; Suyen, G.; Ovali, E.

doi:10.1101/2020.10.28.356667

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bioRxiv · 10.1101/2020.10.28.356667

Gamma-irradiated SARS-CoV-2 vaccine candidate, OZG-38.61.3, confers protection from SARS-CoV-2 challenge in human ACEII-transgenic mice

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Abstract

The SARS-CoV-2 virus caused the most severe pandemic around the world, and vaccine development for urgent use became a crucial issue. Inactivated virus formulated vaccines such as Hepatitis A, oral polio vaccine, and smallpox proved to be reliable approaches for immunization for prolonged periods. During the pandemic, we produced an inactivated SARS-CoV-2 vaccine candidate, having the advantages of being manufactured rapidly and tested easily in comparison with recombinant vaccines. In this study, an inactivated virus vaccine that includes a gamma irradiation process for the inactivation as an alternative to classical chemical inactivation methods so that there is no extra purification required has been optimized. The vaccine candidate (OZG-38.61.3) was then applied in mice by employing the intradermal route, which decreased the requirement of a higher concentration of inactivated virus for proper immunization, unlike most of the classical inactivated vaccine treatments. Hence, the novelty of our vaccine candidate (OZG-38.61.3) is that it is a non-adjuvant added, gamma-irradiated, and intradermally applied inactive viral vaccine. Efficiency and safety dose (either 1013 or 1014 viral copy per dose) of OZG-38.61.3 was initially determined in Balb/c mice. This was followed by testing the immunogenicity and protective efficacy of OZG-38.61.3. Human ACE2-encoding transgenic mice were immunized and then infected with a dose of infective SARS-CoV-2 virus for the challenge test. Findings of this study show that vaccinated mice have lower SARS-CoV-2 viral copy number in oropharyngeal specimens along with humoral and cellular immune responses against the SARS-CoV-2, including the neutralizing antibodies similar to those shown in Balb/c mice without substantial toxicity. Subsequently, plans are being made for the commencement of Phase 1 clinical trial of the OZG-38.61.3 vaccine for the COVID-19 pandemic.

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Turan, R. D., Tastan, C., Dilek Kancagi, D., Yurtsever, B., Sir Karakus, G., Ozer, S., Abanuz, S., Cakirsoy, D., Tumentemur, G., Demir, S., Seyis, U., Kuzay, R., Elek, M., Ertop, G., Arbak, S., Acikel Elmas, M., Hemsinlioglu, C., Hatirnaz Ng, O., Akyoney, S., Sahin, I., Kayhan, C. K., Tokat, F., Akpinar, G., Kasap, M., Kocagoz, A. S., Ozbek, U., Telci, D., Sahin, F., Yalcin, K., Ratip, S., Ince, U., Suyen, G., Ovali, E.. 2020-10-28. Gamma-irradiated SARS-CoV-2 vaccine candidate, OZG-38.61.3, confers protection from SARS-CoV-2 challenge in human ACEII-transgenic mice. https://doi.org/10.1101/2020.10.28.356667

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