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

Abstract

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 Mycobacterium bovis 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 naïve 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.

Could BCG Vaccination Induce Protective Trained Immunity for SARS-CoV-2?

“…The Netherlands and Germany show a significant increase in their confirmed cases per million inhabitants, suggesting that the contagion curve will increase similar to the Italian, Spanish, and American ones. A common feature of these countries is that they do not include BCG in their national vaccination programs, so we speculate that this vaccine may have a protective role in the immune defense against respiratory diseases (36)(37)(38)(39)(40)(41). Utilizing the WHO immunization monitoring data (9), we elaborated the graphs shown in Figures 2B-D comparing the contagion and mortality rates due to COVID-19 between countries with or without administration of BCG in their national vaccination programs.…”

New disease old vaccine: Is recombinant BCG vaccine an answer for COVID-19?

“…In a recent study, rBCG- N -hRSV which expresses the nucleoprotein (N) of the human respiratory syncytial virus (hRSV), protected mice from hRSV challenge by induction of hRSV specific neutralizing antibodies and reduced the clinical pathology of the lung [57] .…”

Current Insights in the Development of Efficacious Vaccines Against RSV

“…A similar induction of serum neutralizing antibodies was observed with a cold-passage/stabilized RSV containing several attenuating point mutations as well as deletion of the small hydrophobic (SH) protein (RSVcps2) ( 21 ). Finally, preclinical studies of a recombinant BCG vaccine expressing the RSV nucleoprotein (N) demonstrated an effective cellular and humoral immune response in mice ( 22 – 25 ).…”

“…One of the most common viral targets for antibodies is the RSV fusion (F) protein ( 38 , 39 ). Vaccine formulations containing the N protein also induce long-lasting neutralizing antibodies and could serve as a novel antiviral target ( 22 , 25 ). The RSV G protein is involved in the initiation of the virus life cycle and has a potent effect on the regulation of the immune response ( 36 ).…”