Recombinant BCG Vaccines Reduce Pneumovirus-Caused Airway Pathology by Inducing Protective Humoral Immunity

• Published in: Frontiers in immunology Vol. 9; p. 2875
• Main Authors: Soto, Jorge A, Gálvez, Nicolás M S, Rivera, Claudia A, Palavecino, Christian E, Céspedes, Pablo F, Rey-Jurado, Emma, Bueno, Susan M, Kalergis, Alexis M
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 06.12.2018
• Subjects: Animals; antibodies; BCG Vaccine - administration & dosage; BCG Vaccine - immunology; Cell Line, Tumor; Disease Models, Animal; hMPV; hRSV; Humans; humoral immune response; Immunity, Humoral; Immunology; Metapneumovirus - genetics; Metapneumovirus - immunology; Mice; Mice, Inbred BALB C; Mycobacterium bovis - immunology; Nucleoproteins - administration & dosage; Nucleoproteins - genetics; Nucleoproteins - immunology; Recombinant Proteins - administration & dosage; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Respiratory Syncytial Virus, Human - genetics; Respiratory Syncytial Virus, Human - immunology; Respiratory Tract Infections - immunology; Respiratory Tract Infections - prevention & control; Respiratory Tract Infections - virology; respiratory virus; Th1 Cells - immunology; Th1 Cells - metabolism; Vaccination - methods; vaccine; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - immunology; Viral Proteins - administration & dosage; Viral Proteins - genetics; Viral Proteins - immunology; Virus Replication - immunology; vaccine; respiratory virus; BCG; antibodies; hMPV; humoral immune response; hRSV
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.02875

The Human Respiratory Syncytial Virus (hRSV) and the Human Metapneumovirus (hMPV) are two pneumoviruses that are leading agents causing acute lower respiratory tract infections (ALRTIs) affecting young infants, the elderly, and immunocompromised patients worldwide. Since these pathogens were first discovered, many approaches for the licensing of safe and effective vaccines have been explored being unsuccessful to date. We have previously described that immunization with recombinant strains of Bacillus Calmette-Guérin (rBCG) expressing the hRSV nucleoprotein (rBCG-N) or the hMPV phosphoprotein (rBCG-P) induced immune protection against each respective virus. These vaccines efficiently promoted viral clearance without significant lung damage, mainly through the induction of a T helper 1 cellular immunity. Here we show that upon viral challenge, rBCG-immunized mice developed a protective humoral immunity, characterized by production of antibodies specific for most hRSV and hMPV proteins. Further, isotype switching from IgG1 to IgG2a was observed in mice immunized with rBCG vaccines and correlated with an increased viral clearance, as compared to unimmunized animals. Finally, sera obtained from animals immunized with rBCG vaccines and infected with their respective viruses exhibited virus neutralizing capacity and protected mice from viral replication and pulmonary disease. These results support the notion that the use of rBCG strains could be considered as an effective vaccination approach against other respiratory viruses with similar biology as hRSV and hMPV.