biostudies-literatureMambelli FFundação de Amparo à Pesquisa do Estado de Minas GeraisConselho Nacional de Desenvolvimento Científico e TecnológicoHoward Hughes Medical InstituteCoordenação de Aperfeiçoamento de Pessoal de Nível SuperiorNIAID NIH HHSFundação de Amparo à Pesquisa do Estado de São PauloUSP | Pro-Reitoria de Pesquisa, Universidade de São Paulo1925-1937https://www.ebi.ac.uk/biostudies/studies/S-EPMC10247535biostudies-literatureUnknown210(12)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.Journal of immunology (Baltimore, Md. : 1950)Recombinant Bacillus Calmette-Guerin Expressing SARS-CoV-2 Chimeric Protein Protects K18-hACE2 Mice against Viral Challenge.PMC10247535R01 AI1164535500741288887.504421/2020-00465229/2014-0303044/2020-988887.506612/2020-002023/02577-52017/24832-6REDE-00140-16401209/2020-2Dias GBMAndrade JMHoman EJSantos BPOAbuna RPFHeck NLeite LCCMendes DAGBde Araujo ACVSCMansur DSBafica AFabri VMROliveira SCda Silva JSMambelli Fde Magalhaes MTQMarinho FVfalseRecombinant Bacillus Calmette-Guerin Expressing SARS-CoV-2 Chimeric Protein Protects K18-hACE2 Mice against Viral Challenge.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.2023-01-01T00:00:00Z2023 Jun2026-06-02T06:40:04.092Z2026-05-25T03:07:32.102ZS-EPMC102475353709889010.4049/jimmunol.2200731