A recombinant bovine adenoviral mucosal vaccine expressing mycobacterial antigen-85B generates robust protection against tuberculosis in mice

Arshad Khan, Ekramy E. Sayedahmed, Vipul K. Singh, Abhishek Mishra, Stephanie Dorta-Estremera, Sita Nookala, David H. Canaday, Min Chen, Jin Wang, K. Jagannadha Sastry, Suresh K. Mittal, Chinnaswamy Jagannath

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Although the BCG vaccine offers partial protection, tuberculosis remains a leading cause of infectious disease death, killing ∼1.5 million people annually. We developed mucosal vaccines expressing the autophagy-inducing peptide C5 and mycobacterial Ag85B-p25 epitope using replication-defective human adenovirus (HAdv85C5) and bovine adenovirus (BAdv85C5) vectors. BAdv85C5-infected dendritic cells (DCs) expressed a robust transcriptome of genes regulating antigen processing compared to HAdv85C5-infected DCs. BAdv85C5-infected DCs showed enhanced galectin-3/8 and autophagy-dependent in vitro Ag85B-p25 epitope presentation to CD4 T cells. BCG-vaccinated mice were intranasally boosted using HAdv85C5 or BAdv85C5 followed by infection using aerosolized Mycobacterium tuberculosis (Mtb). BAdv85C5 protected mice against tuberculosis both as a booster after BCG vaccine (>1.4-log10 reduction in Mtb lung burden) and as a single intranasal dose (>0.5-log10 reduction). Protection was associated with robust CD4 and CD8 effector (TEM), central memory (TCM), and CD103+/CD69+ lung-resident memory (TRM) T cell expansion, revealing BAdv85C5 as a promising mucosal vaccine for tuberculosis.

Original languageEnglish (US)
Article number100372
Pages (from-to)100372
JournalCell Reports Medicine
Volume2
Issue number8
DOIs
StatePublished - Aug 17 2021

Keywords

  • antigen presentation
  • autophagy
  • BAdv
  • BCG vaccine
  • bovine adenovirus
  • C57BL/6 mice
  • dendritic cells
  • galectin-3/8
  • HAdv
  • human adenovirus
  • mucosal vaccine
  • Mycobacterium tuberculosis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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