TY - JOUR
T1 - Identification and Evaluation of Recombinant Outer Membrane Proteins as Vaccine Candidates Against Klebsiella pneumoniae
AU - Zhang, Bao Zhong
AU - Hu, Danyu
AU - Dou, Ying
AU - Xiong, Lifeng
AU - Wang, Xiaolei
AU - Hu, Jingchu
AU - Xing, Shao Zhen
AU - Li, Wenjun
AU - Cai, Jian Piao
AU - Jin, Meiling
AU - Zhang, Mengya
AU - Lin, Qiubin
AU - Li, Min
AU - Yuen, Kwok Yung
AU - Huang, Jian Dong
N1 - Funding Information:
This work was supported by the National Key Research and Development Program (2018YFA0903000), the Shenzhen Peacock project (KQTD2015033117210153), and Health and Medical Research Fund (HMRF, HKM-15-M09).
Publisher Copyright:
Copyright © 2021 Zhang, Hu, Dou, Xiong, Wang, Hu, Xing, Li, Cai, Jin, Zhang, Lin, Li, Yuen and Huang.
PY - 2021/10/20
Y1 - 2021/10/20
N2 - Klebsiella pneumoniae found in the normal flora of the human oral and intestinal tract mainly causes hospital-acquired infections but can also cause community-acquired infections. To date, most clinical trials of vaccines against K. pneumoniae have ended in failure. Furthermore, no single conserved protein has been identified as an antigen candidate to accelerate vaccine development. In this study, we identified five outer membrane proteins of K. pneumoniae, namely, Kpn_Omp001, Kpn_Omp002, Kpn_Omp003, Kpn_Omp004, and Kpn_Omp005, by using reliable second-generation proteomics and bioinformatics. Mice vaccinated with these five KOMPs elicited significantly higher antigen-specific IgG, IgG1, and IgG2a. However, only Kpn_Omp001, Kpn_Omp002, and Kpn_Omp005 were able to induce a protective immune response with two K. pneumoniae infection models. These protective effects were accompanied by the involvement of different immune responses induced by KOMPs, which included KOMPs-specific IFN-γ-, IL4-, and IL17A-mediated immune responses. These findings indicate that Kpn_Omp001, Kpn_Omp002, and Kpn_Omp005 are three potential Th1, Th2, and Th17 candidate antigens, which could be developed into multivalent and serotype-independent vaccines against K. pneumoniae infection.
AB - Klebsiella pneumoniae found in the normal flora of the human oral and intestinal tract mainly causes hospital-acquired infections but can also cause community-acquired infections. To date, most clinical trials of vaccines against K. pneumoniae have ended in failure. Furthermore, no single conserved protein has been identified as an antigen candidate to accelerate vaccine development. In this study, we identified five outer membrane proteins of K. pneumoniae, namely, Kpn_Omp001, Kpn_Omp002, Kpn_Omp003, Kpn_Omp004, and Kpn_Omp005, by using reliable second-generation proteomics and bioinformatics. Mice vaccinated with these five KOMPs elicited significantly higher antigen-specific IgG, IgG1, and IgG2a. However, only Kpn_Omp001, Kpn_Omp002, and Kpn_Omp005 were able to induce a protective immune response with two K. pneumoniae infection models. These protective effects were accompanied by the involvement of different immune responses induced by KOMPs, which included KOMPs-specific IFN-γ-, IL4-, and IL17A-mediated immune responses. These findings indicate that Kpn_Omp001, Kpn_Omp002, and Kpn_Omp005 are three potential Th1, Th2, and Th17 candidate antigens, which could be developed into multivalent and serotype-independent vaccines against K. pneumoniae infection.
KW - Klebsiella pneumoniae
KW - outer membrane proteins
KW - proteomics and bioinformatics
KW - serotype-independent vaccines
KW - vaccine
UR - http://www.scopus.com/inward/record.url?scp=85118657045&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2021.730116
DO - 10.3389/fimmu.2021.730116
M3 - Journal article
C2 - 34745099
AN - SCOPUS:85118657045
SN - 1664-3224
VL - 12
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 730116
ER -
