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

Author(s):Show less -

Mambelli, Fabio ; Marinho, Fabio V. ; Andrade, Juvana M. ; de Araujo, Ana C. V. S. C. ; Abuna, Rodrigo P. F. ; Fabri, Victor M. R. ; Santos, Bruno P. O. ; da Silva, Joao S. ; de Magalhaes, Mariana T. Q. ; Homan, E. Jane ; Leite, Luciana C. C. ; Dias, Greicy B. M. ; Heck, Nicoli ; Mendes, Daniel A. G. B. ; Mansur, Daniel S. ; Bafica, Andre ; Oliveira, Sergio C.

• Document type: Journal article
• Source: JOURNAL OF IMMUNOLOGY; v. 210, n. 12, p. 13-pg., 2023-06-15.

Abstract

COVID-19 has accounted for more than 6 million deaths worldwide. Bacillus Calmette-Guerin (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-gamma 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. (AU)

• FAPESP's process: 23/02577-5 - Study of the mechanisms responsible for trained immunity induced by Bacillus Calmette-Guérin (BCG) in infectious diseases and Cancer
• Grantee: Sergio Costa Oliveira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/24832-6 - Development of vaccines based on recombinant BCG: Tuberculosis, Pertussis, Pneumococcus and Schistosoma
• Grantee: Luciana Cezar de Cerqueira Leite
• Support Opportunities: Research Projects - Thematic Grants