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

doi:10.1016/j.xcrm.2021.100372

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 journal › Article › peer-review

20 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 (HAdv^85C5) and bovine adenovirus (BAdv^85C5) vectors. BAdv^85C5-infected dendritic cells (DCs) expressed a robust transcriptome of genes regulating antigen processing compared to HAdv^85C5-infected DCs. BAdv^85C5-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 HAdv^85C5 or BAdv^85C5 followed by infection using aerosolized Mycobacterium tuberculosis (Mtb). BAdv^85C5 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 (T_EM), central memory (T_CM), and CD103⁺/CD69⁺ lung-resident memory (T_RM) T cell expansion, revealing BAdv^85C5 as a promising mucosal vaccine for tuberculosis.

Original language	English (US)
Article number	100372
Pages (from-to)	100372
Journal	Cell Reports Medicine
Volume	2
Issue number	8
DOIs	https://doi.org/10.1016/j.xcrm.2021.100372
State	Published - Aug 17 2021

Keywords

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

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.xcrm.2021.100372

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Khan, A., Sayedahmed, E. E., Singh, V. K., Mishra, A., Dorta-Estremera, S., Nookala, S., Canaday, D. H., Chen, M., Wang, J., Sastry, K. J., Mittal, S. K., & Jagannath, C. (2021). A recombinant bovine adenoviral mucosal vaccine expressing mycobacterial antigen-85B generates robust protection against tuberculosis in mice. Cell Reports Medicine, 2(8), 100372. Article 100372. https://doi.org/10.1016/j.xcrm.2021.100372

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 2021, 'A recombinant bovine adenoviral mucosal vaccine expressing mycobacterial antigen-85B generates robust protection against tuberculosis in mice', Cell Reports Medicine, vol. 2, no. 8, 100372, pp. 100372. https://doi.org/10.1016/j.xcrm.2021.100372

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

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.",

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

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

note = "Funding Information: This work was supported in part by NIH grant AI122070 (principal investigator, C.J.) and supporting funds from the Houston Methodist Academy of Medicine . This work was partially supported by the Hatch funds (principal investigator, S.K.M.). We thank Ahmed Hassan for generating some of the Adv vectors. We are grateful to Drs. Pejerrey and McConnell for editing the manuscript. Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = aug,

day = "17",

doi = "10.1016/j.xcrm.2021.100372",

language = "English (US)",

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pages = "100372",

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T1 - A recombinant bovine adenoviral mucosal vaccine expressing mycobacterial antigen-85B generates robust protection against tuberculosis in mice

AU - Khan, Arshad

AU - Sayedahmed, Ekramy E.

AU - Singh, Vipul K.

AU - Mishra, Abhishek

AU - Dorta-Estremera, Stephanie

AU - Nookala, Sita

AU - Canaday, David H.

AU - Chen, Min

AU - Wang, Jin

AU - Sastry, K. Jagannadha

AU - Mittal, Suresh K.

AU - Jagannath, Chinnaswamy

N1 - Funding Information: This work was supported in part by NIH grant AI122070 (principal investigator, C.J.) and supporting funds from the Houston Methodist Academy of Medicine . This work was partially supported by the Hatch funds (principal investigator, S.K.M.). We thank Ahmed Hassan for generating some of the Adv vectors. We are grateful to Drs. Pejerrey and McConnell for editing the manuscript. Publisher Copyright: © 2021 The Authors

PY - 2021/8/17

Y1 - 2021/8/17

N2 - 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.

AB - 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.

KW - BAdv

KW - BCG vaccine

KW - C57BL/6 mice

KW - HAdv

KW - Mycobacterium tuberculosis

KW - antigen presentation

KW - autophagy

KW - bovine adenovirus

KW - dendritic cells

KW - galectin-3/8

KW - human adenovirus

KW - mucosal vaccine

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DO - 10.1016/j.xcrm.2021.100372

M3 - Article

C2 - 34467249

AN - SCOPUS:85111620883

SN - 2666-3791

VL - 2

SP - 100372

JO - Cell Reports Medicine

JF - Cell Reports Medicine

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ER -

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

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