gB co-immunization with GP96 enhances pulmonary-resident CD8 T cells and exerts a long-term defence against MCMV pneumonitis

被引:2
作者
Guo, Bingnan [1 ,2 ]
Xu, Peifeng [3 ]
Chai, Dafei [4 ]
Cao, Lei [1 ,2 ]
Liu, Lin [1 ,2 ]
Song, Tengfei [5 ]
Hu, Shuqun [1 ,2 ]
Chen, Yuling [3 ]
Yan, Xianliang [1 ,2 ]
Xu, Tie [1 ,2 ,6 ]
机构
[1] Xuzhou Med Univ, Jiangsu Inst Hlth Emergency, Xuzhou 221000, Jiangsu, Peoples R China
[2] Xuzhou Med Univ, Emergency Ctr, Affiliated Hosp, Xuzhou 221000, Jiangsu, Peoples R China
[3] Xuzhou Med Univ, Dept Resp Med, Affiliated Hosp, Xuzhou, Jiangsu, Peoples R China
[4] Xuzhou Med Univ, Canc Inst, Xuzhou, Jiangsu, Peoples R China
[5] Feinstein Inst Med Res, New York, NY USA
[6] Nanjing Jiangning Hosp, Dept Emergency, Nanjing 210000, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
cytomegalovirus; DNA vaccine; GP96; pneumonitis; pulmonary‐ resident CD8 T cell; MURINE CYTOMEGALOVIRUS; DNA VACCINE; MUCOSAL IMMUNIZATION; VIRAL REPLICATION; CMV INFECTION; PROTECTION; TISSUE; IMMUNITY; RESPONSES; ADJUVANT;
D O I
10.1111/jcmm.16065
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Human cytomegalovirus (HCMV) infection in the respiratory tract leads to pneumonitis in immunocompromised hosts without available vaccine. Considering cytomegalovirus (CMV) mainly invades through the respiratory tract, CMV-specific pulmonary mucosal vaccine development that provides a long-lasting protection against CMV challenge gains our attention. In this study, N-terminal domain of GP96 (GP96-NT) was used as a mucosal adjuvant to enhance the induction of pulmonary-resident CD8 T cells elicited by MCMV glycoprotein B (gB) vaccine. Mice were intranasally co-immunized with 50 mu g pgB and equal amount of pGP96-NT vaccine 4 times at 2-week intervals, and then i.n. challenged with MCMV at 16 weeks after the last immunization. Compared with pgB immunization alone, co-immunization with pgB/pGP96-NT enhanced a long-lasting protection against MCMV pneumonitis by significantly improved pneumonitis pathology, enhanced bodyweight, reduced viral burdens and increased survival rate. Moreover, the increased CD8 T cells were observed in lung but not spleen from pgB/pGP96-NT co-immunized mice. The increments of pulmonary CD8 T cells might be mainly due to non-circulating pulmonary-resident CD8 T-cell subset expansion but not circulating CD8 T-cell populations that home to inflammation site upon MCMV challenge. Finally, the deterioration of MCMV pneumonitis by depletion of pulmonary site-specific CD8 T cells in mice that were pgB/pGP96-NT co-immunization might be a clue to interpret the non-circulating pulmonary-resident CD8 T subset expansion. These data might uncover a promising long-lasting prophylactic vaccine strategy against MCMV-induced pneumonitis.
引用
收藏
页码:14426 / 14440
页数:15
相关论文
共 60 条
[1]   The Potential Harm of Cytomegalovirus Infection in Immunocompetent Critically Ill Children [J].
Alyazidi, Raidan ;
Murthy, Srinivas ;
Slyker, Jennifer A. ;
Gantt, Soren .
FRONTIERS IN PEDIATRICS, 2018, 6
[2]   Cytomegalovirus Vaccines: Current Status and Future Prospects [J].
Anderholm, K. M. ;
Bierle, C. J. ;
Schleiss, M. R. .
DRUGS, 2016, 76 (17) :1625-1645
[3]   Intravascular staining for discrimination of vascular and tissue leukocytes [J].
Anderson, Kristin G. ;
Mayer-Barber, Katrin ;
Sung, Heungsup ;
Beura, Lalit ;
James, Britnie R. ;
Taylor, Justin J. ;
Qunaj, Lindor ;
Griffith, Thomas S. ;
Vezys, Vaiva ;
Barber, Daniel L. ;
Masopust, David .
NATURE PROTOCOLS, 2014, 9 (01) :209-222
[4]   A non-pathogenic Leishmania tarentolae vector based- HCV polytope DNA vaccine elicits potent and long lasting Th1 and CTL responses in BALB/c mice model [J].
Ansari, Nastaran ;
Rafati, Sima ;
Taheri, Tahereh ;
Roohvand, Farzin ;
Farahmand, Mohammad ;
Hajikhezri, Zamaneh ;
Keshavarz, Abolfazl ;
Samimi-Rad, Katayoun .
MOLECULAR IMMUNOLOGY, 2019, 111 :152-161
[5]   Leukocyte compartments in the mouse lung: Distinguishing between marginated, interstitial, and alveolar cells in response to injury [J].
Barletta, Kathryn E. ;
Cagnina, R. Elaine ;
Wallace, Kori L. ;
Ramos, Susan I. ;
Mehrad, Borna ;
Linden, Joel .
JOURNAL OF IMMUNOLOGICAL METHODS, 2012, 375 (1-2) :100-110
[6]   Pulmonary DNA vaccination: Concepts, possibilities and perspectives [J].
Bivas-Benita, M ;
Ottenhoff, THM ;
Junginger, HE ;
Borchard, G .
JOURNAL OF CONTROLLED RELEASE, 2005, 107 (01) :1-29
[7]   Cytomegalovirus (CMV) Pneumonitis: Cell Tropism, Inflammation, and Immunity [J].
Brito, Luis Fonseca ;
Brune, Wolfram ;
Stahl, Felix R. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2019, 20 (16)
[8]   Replication-defective lymphocytic choriomeningitis virus vectors expressing guinea pig cytomegalovirus gB and pp65 homologs are protective against congenital guinea pig cytomegalovirus infection [J].
Cardin, Rhonda D. ;
Bravo, Fernando J. ;
Pullum, Derek A. ;
Orlinger, Klaus ;
Watson, Elizabeth M. ;
Aspoeck, Andreas ;
Fuhrmann, Gerhard ;
Guirakhoo, Farshad ;
Monath, Thomas ;
Bernstein, David I. .
VACCINE, 2016, 34 (17) :1993-1999
[9]   A Novel Non-Replication-Competent Cytomegalovirus Capsid Mutant Vaccine Strategy Is Effective in Reducing Congenital Infection [J].
Choi, K. Yeon ;
Root, Matthew ;
McGregor, Alistair .
JOURNAL OF VIROLOGY, 2016, 90 (17) :7902-7919
[10]   Life-long control of cytomegalovirus (CMV) by T resident memory cells in the adipose tissue results in inflammation and hyperglycemia [J].
Contreras, Nico A. ;
Sitnik, Katarzyna M. ;
Jeftic, Ilija ;
Coplen, Christopher Patrick ;
Cicin-Sain, Luka ;
Nikolich-Zugich, Janko .
PLOS PATHOGENS, 2019, 15 (06)