Immunization with SARS-CoV-2 nucleocapsid protein triggers a pulmonary immune response in rats

Silva, E. K. V. B.; Bomfim, C. G.; Barbosa, A. P.; Noda, P.; Noronha, I. L.; Fernandes, B. H. V.; Machado, R. R. G.; Durigon, E. L.; Catanozi, S.; Rodrigues, L. G.; Pieroni, F.; Lima, S.; Queiroz, Z. A. J.; Charlie-Silva, I.; Silveira, L. K. R.; Teodoro, W. T.; Capelozzi, V. L.; Guzzo, C. R.; Fanelli, C.

doi:10.1101/2021.08.24.457520

bioRxiv · 10.1101/2021.08.24.457520

Immunization with SARS-CoV-2 nucleocapsid protein triggers a pulmonary immune response in rats

Silva, E. K. V. B.·Bomfim, C. G.·Barbosa, A. P.·Noda, P.·Noronha, I. L.·Fernandes, B. H. V.·Machado, R. R. G.·Durigon, E. L.·Catanozi, S.·Rodrigues, L. G.·Pieroni, F.·Lima, S.·Queiroz, Z. A. J.·Charlie-Silva, I.·Silveira, L. K. R.·Teodoro, W. T.·Capelozzi, V. L.·Guzzo, C. R.·Fanelli, C.

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Abstract

The SARS-CoV-2 pandemic have been affecting millions of people worldwide, since the beginning of 2020. COVID-19 can cause a wide range of clinical symptoms, which varies from asymptomatic presentation to severe respiratory insufficiency, exacerbation of immune response, disseminated microthrombosis and multiple organ failure, which may lead to dead. Due to the rapid spread of SARS-CoV-2, the development of vaccines to minimize COVID-19 severity in the world population is imperious. One of the employed techniques to produce vaccines against emerging viruses is the synthesis of recombinant proteins, which can be used as immunizing agents. Based on the exposed, the aim of the present study was to verify the systemic and immunological effects of IM administration of recombinant Nucleocapsid protein (NP), derived from SARS-CoV-2 and produced by this research group, in 2 different strains of rats (Rattus norvegicus); Wistar and Lewis. For this purpose, experimental animals received 4 injections of NP, once a week, and were submitted to biochemical and histological analysis. Our results showed that NP inoculations were safe for the animals, which presented no clinical symptoms of worrying side effects, nor laboratorial alterations in the main biochemical and histological parameters, suggesting the absence of toxicity induced by NP. Moreover, NP injections successfully triggered the production of specific anti-SARS-CoV-2 IgG antibodies by both Wistar and Lewis rats, showing the sensitization to have been well sufficient for the immunization of these strains of rats. Additionally, we observed the local lung activation of the Bronchus-Associated Lymphoid Tissue (BALT) of rats in the NP groups, suggesting that NP elicits specific lung immune response. Although pre-clinical and clinical studies are still required, our data support the recombinant NP produced by this research group as a potential immunizing agent for massive vaccination, and may represent advantages upon other recombinant proteins, since it seems to induce specific pulmonary protection.

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Silva, E. K. V. B., Bomfim, C. G., Barbosa, A. P., Noda, P., Noronha, I. L., Fernandes, B. H. V., Machado, R. R. G., Durigon, E. L., Catanozi, S., Rodrigues, L. G., Pieroni, F., Lima, S., Queiroz, Z. A. J., Charlie-Silva, I., Silveira, L. K. R., Teodoro, W. T., Capelozzi, V. L., Guzzo, C. R., Fanelli, C.. 2021-08-24. Immunization with SARS-CoV-2 nucleocapsid protein triggers a pulmonary immune response in rats. https://doi.org/10.1101/2021.08.24.457520

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