BCG-Based Vaccines Elicit Antigen-Specific Adaptive and Trained Immunity against SARS-CoV-2 and Andes orthohantavirus

• Published in: Vaccines (Basel) 2022-05, Vol.10 (5), p.721
• Main Authors: Soto, Jorge A, Díaz, Fabián E, Retamal-Díaz, Angello, Gálvez, Nicolás M S, Melo-González, Felipe, Piña-Iturbe, Alejandro, Ramírez, Mario A, Bohmwald, Karen, González, Pablo A, Bueno, Susan M, Kalergis, Alexis M
• Format: Article
• Language: English
• Subjects: Andes orthohantavirus; Antibodies; Antigens; CD4 antigen; CD8 antigen; Cell activation; Cloning; Coronaviruses; COVID-19; Cytokines; Disease transmission; Fever; Genes; Genomes; Humoral immunity; Immune response; Immune response (cell-mediated); Immune response (humoral); Immune system; Immunity; Immunization; Immunogenicity; Infections; Interleukin 2; Interleukin 6; Lymphocytes; Lymphocytes T; Neonates; Parameters; Pathogens; Proteins; recombinant BCG; RNA polymerase; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Statistical analysis; trained immunity; Tuberculosis; Vaccines; Viral diseases; Viral infections; Viruses; γ-Interferon
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines10050721

Bacillus Calmette-Guérin (BCG) is a live attenuated vaccine mainly administered to newborns and used for over 100 years to prevent the disease caused by ( ). This vaccine can induce immune response polarization towards a Th1 profile, which is desired for counteracting , other mycobacteria, and unrelated intracellular pathogens. The vaccine BCG has been used as a vector to express recombinant proteins and has been shown to protect against several diseases, particularly respiratory viruses. BCG was used to develop recombinant vaccines expressing either the Nucleoprotein from SARS-CoV-2 or . Mice were immunized with these vaccines with the aim of evaluating the safety and immunogenicity parameters. Immunization with two doses of 1 × 10 CFU or one dose of 1 × 10 CFU of these BCGs was safe in mice. A statistically significant cellular immune response was induced by both formulations, characterized as the activation of CD4 and CD8 T cells. Stimulation with unrelated antigens resulted in increased expression of activation markers by T cells and secretion of IL-2 and IFN-γ, while increased secretion of IL-6 was found for both recombinant vaccines; all of these parameters related to a trained immunity profile. The humoral immune response elicited by both vaccines was modest, but further exposure to antigens could increase this response. The BCG vaccine is a promising platform for developing vaccines against different pathogens, inducing a marked antigen-specific immune response.