A recombinant bovine adenoviral mucosal vaccine expressing mycobacterial antigen-85B generates robust protection against tuberculosis in mice.
A recombinant bovine adenoviral mucosal vaccine expressing mycobacterial antigen-85B generates robust protection against tuberculosis in mice.
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DOI：
10.1016/j.xcrm.2021.100372
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发表时间：
2021-08-17
期刊：
影响因子：
--
通讯作者：
Jagannath C
中科院分区：
文献类型：
--
作者：
Khan A;Sayedahmed EE;Singh VK;Mishra A;Dorta-Estremera S;Nookala S;Canaday DH;Chen M;Wang J;Sastry KJ;Mittal SK;Jagannath C
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. BCG-vaccinated infants need a booster for better protection against tuberculosis The BAdv85C5 vaccine increased protection in BCG-vaccinated mice against tuberculosis The BAdv85C5 vaccine increased antigen presentation and memory T cells responses Mucosal vaccination strengthens lung defense against tuberculosis Khan et al. describe a bovine-adenovirus-based BAdv85C5 mucosal vaccine, which induced a galectin 3/8-dependent autophagy increasing antigen presentation in dendritic cells ex vivo. BAdv85C5 nasal booster in BCG-vaccinated mice enhanced the protection against tuberculosis and increased antigen-specific CD4 T cells and memory T cells.
影响因子：
7.3
作者：
Münz C
通讯作者：
Münz C
影响因子：
3
作者：
Lee JA;Sinkovits RS;Mock D;Rab EL;Cai J;Yang P;Saunders B;Hsueh RC;Choi S;Subramaniam S;Scheuermann RH;Alliance for Cellular Signaling
通讯作者：
Alliance for Cellular Signaling