Induction of Protective Immunity by a Single Low Dose of a Master Cell Bank cGMP-rBCG-P Vaccine Against the Human Metapneumovirus in Mice

Jorge A. Soto, Nicolás M.S. Gálvez, Gaspar A. Pacheco, Gisela Canedo-Marroquín, Susan M. Bueno, Alexis M. Kalergis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Human metapneumovirus (hMPV) is an emergent virus, which mainly infects the upper and lower respiratory tract epithelium. This pathogen is responsible for a significant portion of hospitalizations due to bronchitis and pneumonia in infants and the elderly worldwide. hMPV infection induces a pro-inflammatory immune response upon infection of the host, which is not adequate for the clearance of this pathogen. The lack of knowledge regarding the different molecular mechanisms of infection of this virus has delayed the licensing of effective treatments or vaccines. As part of this work, we evaluated whether a single and low dose of a recombinant Mycobacterium bovis Bacillus Calmette-Guérin (BCG) expressing the phosphoprotein of hMPV (rBCG-P) can induce a protective immune response in mice. Immunization with the rBCG-P significantly decreased neutrophil counts and viral loads in the lungs of infected mice at different time points. This immune response was also associated with a modulated infiltration of innate cells into the lungs, such as interstitial macrophages (IM) and alveolar macrophages (AM), activated CD4+ and CD8+ T cells, and changes in the population of differentiated subsets of B cells, such as marginal zone B cells and plasma cells. The humoral immune response induced by the rBCG-P led to an early and robust IgA response and a late and constant IgG response. Finally, we determined that the transfer of cells or sera from immunized and infected mice to naïve mice promoted an efficient viral clearance. Therefore, a single and low dose of rBCG-P can protect mice from the disease caused by hMPV, and this vaccine could be a promising candidate for future clinical trials.

Original languageEnglish
Article number662714
JournalFrontiers in Cellular and Infection Microbiology
Volume11
DOIs
StatePublished - 29 Jun 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© Copyright © 2021 Soto, Gálvez, Pacheco, Canedo-Marroquín, Bueno and Kalergis.

Keywords

  • adaptive immunity
  • hMPV
  • human metapneumovirus
  • innate immunity
  • master cell bank cGMP
  • recombinant BCG
  • vaccine

Fingerprint

Dive into the research topics of 'Induction of Protective Immunity by a Single Low Dose of a Master Cell Bank cGMP-rBCG-P Vaccine Against the Human Metapneumovirus in Mice'. Together they form a unique fingerprint.

Cite this