A recombinant bovine adenoviral mucosal vaccine expressing mycobacterial antigen-85B generates robust protection against tuberculosis in mice.
Cell Rep Med
; 2(8): 100372, 2021 08 17.
Article
em En
| MEDLINE
| ID: mdl-34467249
ABSTRACT
Although the BCG vaccine offers partial protection, tuberculosis remains a leading cause of infectious disease death, killing â¼1.5 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vacinas Sintéticas
/
Adenoviridae
/
Vacinas contra a Tuberculose
/
Mucosa
/
Mycobacterium tuberculosis
/
Antígenos de Bactérias
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article