Recombinant bacillus calmette–guérin expressing SARS-CoV-2 chimeric protein protects K18-hACE2 mice against viral challenge
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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.
Mambelli F, Marinho FV., Andrade JM., Leite LCC. Recombinant bacillus calmette–guérin expressing SARS-CoV-2 chimeric protein protects K18-hACE2 mice against viral challenge. J Immunol. 2023 Apr; 210(12):1925–1937. doi:10.4049/jimmunol.2200731.
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(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico ; (CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior ; (FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo ; Howard Hughes Medical Institute ; (FAPEMIG) Fundação de Amparo à Pesquisa do Estado de Minas Gerais
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