Recombinant Bacillus Calmette–Guérin Expressing SARS-CoV-2 Chimeric Protein Protects K18-hACE2 Mice against Viral Challenge

Autor: Fábio Mambelli, Fábio V. Marinho, Juvana M. Andrade, Ana C. V. S. C. de Araujo, Rodrigo P. F. Abuna, Victor M. R. Fabri, Bruno P. O. Santos, João S. da Silva, Mariana T. Q. de Magalhães, E. Jane Homan, Luciana C. C. Leite, Greicy B. M. Dias, Nicoli Heck, Daniel A. G. B. Mendes, Daniel S. Mansur, André Báfica, Sergio C. Oliveira
Rok vydání: 2023
Předmět:
Zdroj: The Journal of Immunology.
ISSN: 1550-6606
0022-1767
Popis: COVID-19 has accounted for more than 6 million deaths worldwide. Bacillus Calmette–Guérin (BCG), the existing tuberculosis vaccine, is known to induce heterologous effects over other infections due to trained immunity and has been proposed to be a potential strategy against SARS-CoV-2 infection. In this report, we constructed a recombinant BCG (rBCG) expressing domains of the SARS-CoV-2 nucleocapsid and spike proteins (termed rBCG-ChD6), recognized as major candidates for vaccine development. We investigated whether rBCG-ChD6 immunization followed by a boost with the recombinant nucleocapsid and spike chimera (rChimera), together with alum, provided protection against SARS-CoV-2 infection in K18-hACE2 mice. A single dose of rBCG-ChD6 boosted with rChimera associated with alum elicited the highest anti-Chimera total IgG and IgG2c Ab titers with neutralizing activity against SARS-CoV-2 Wuhan strain when compared with control groups. Importantly, following SARS-CoV-2 challenge, this vaccination regimen induced IFN-γ and IL-6 production in spleen cells and reduced viral load in the lungs. In addition, no viable virus was detected in mice immunized with rBCG-ChD6 boosted with rChimera, which was associated with decreased lung pathology when compared with BCG WT-rChimera/alum or rChimera/alum control groups. Overall, our study demonstrates the potential of a prime-boost immunization system based on an rBCG expressing a chimeric protein derived from SARS-CoV-2 to protect mice against viral challenge.
Databáze: OpenAIRE
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