Sendai Virus Mucosal Vaccination Establishes Lung-Resident Memory CD8 T Cell Immunity and Boosts BCG-Primed Protection against TB in Mice.
Accumulating evidence has shown the protective role of CD8+T cells in vaccine-induced immunity against Mycobacterium tuberculosis (Mtb) despite controversy over their role in natural immunity. However, the current vaccine BCG is unable to induce sufficient CD8+T cell responses, especially in the lung. Sendai virus, a respiratory RNA virus, is here engineered firstly as a novel recombinant anti-TB vaccine (SeV85AB) that encodes Mtb immuno-dominant antigens, Ag85A and Ag85B. A single mucosal vaccination elicited potent antigen-specific T cell responses and a degree of protection against Mtb challenge similar to the effect of BCG in mice. Depletion of CD8+T cells abrogated the protective immunity afforded by SeV85AB vaccination. Interestingly, only SeV85AB vaccination induced high levels of lung-resident memory CD8+T (TRM) cells, and this led to a rapid and strong recall of antigen-specific CD8+T cell responses against Mtb challenge infection. Furthermore, when used in a BCG prime-SeV85AB boost strategy, SeV85AB vaccine significantly enhanced protection above that seen after BCG vaccination alone. Our findings suggest that CD8+TRMcells that arise in lungs responding to this mucosal vaccination might help to protect against TB, and SeV85AB holds notable promise to improve BCG's protective efficacy in a prime-boost immunization regimen.
Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, 2901 Caolang Road, Shanghai 201508, China; TB Center, Shanghai Emerging and Re-emerging Infectious Disease Institute, Shanghai 201508, China.
Zhidong
Z
Hu
Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, 2901 Caolang Road, Shanghai 201508, China; TB Center, Shanghai Emerging and Re-emerging Infectious Disease Institute, Shanghai 201508, China.
Ka-Wing
KW
Wong
Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, 2901 Caolang Road, Shanghai 201508, China.
Hui-Min
HM
Zhao
School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China.
Han-Li
HL
Wen
Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, 2901 Caolang Road, Shanghai 201508, China.
Ping
P
Ji
Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, 2901 Caolang Road, Shanghai 201508, China.
Hui
H
Ma
Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, 2901 Caolang Road, Shanghai 201508, China.
Kang
K
Wu
Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, 2901 Caolang Road, Shanghai 201508, China; TB Center, Shanghai Emerging and Re-emerging Infectious Disease Institute, Shanghai 201508, China.
Shui-Hua
SH
Lu
Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, 2901 Caolang Road, Shanghai 201508, China.
Feng
F
Li
Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, 2901 Caolang Road, Shanghai 201508, China.
Zhong-Ming
ZM
Li
ID Pharma, Ibaraki 300-2611, Japan.
Tsugumine
T
Shu
Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, 2901 Caolang Road, Shanghai 201508, China; TB Center, Shanghai Emerging and Re-emerging Infectious Disease Institute, Shanghai 201508, China.
Jian-Qing
JQ
Xu
Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, 2901 Caolang Road, Shanghai 201508, China; TB Center, Shanghai Emerging and Re-emerging Infectious Disease Institute, Shanghai 201508, China.
Douglas B
DB
Lowrie
Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, 2901 Caolang Road, Shanghai 201508, China; School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325035, China; TB Center, Shanghai Emerging and Re-emerging Infectious Disease Institute, Shanghai 201508, China. Electronic address: xyfan008@fudan.edu.cn.
Xiao-Yong
XY
Fan
D000217:Acyltransferases / Q000235:genetics / Q000276:immunology; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage*; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D005818:Genetic Engineering; D018928:Immunity, Mucosal; D007117:Immunization, Secondary / Q000379:methods*; D000071497:Immunogenicity, Vaccine; D007156:Immunologic Memory; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity; D020545:Respiratory Mucosa / Q000276:immunology / Q000382:microbiology; D029082:Sendai virus / Q000235:genetics* / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D014611:Vaccination / Q000379:methods*
D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis; C121433:antigen 85B, Mycobacterium tuberculosis
CD8(+) T cell responses; Mycobacterium tuberculosis; Sendai virus; TB vaccine; mucosal immunity; prime boost; resident memory T cells