Mucosal immunization with caseinolytic protease X elicited cross-protective immunity against pneumococcal infection in mice.
Streptococcus pneumoniae resides on the mucosal surface of the upper respiratory tract and is ready to spread and trigger clinical diseases. Hence the vaccine that can eliminate the nasopharyngeal colonization was thought to be an ideal protective strategy against pneumococcal invasive diseases. Caseinolytic protease X (ClpX), a pneumococcal caseinolytic protease ATPase subunit, was shown to be a non-transmembrane protein by bioinformatics analysis. Consistent with the in silico prediction, the secretory expression of ClpX, instead of surface exposure, was further confirmed by flow cytometry and Western blot. Furthermore, ClpX was highly conserved in nine different serotypes of S. pneumoniae at both gene and protein concentrations. In addition, the anti-ClpX IgG antibody levels in human serum samples were much higher in healthy children, compared with pediatric patients, and displayed an age-related increase. Finally, ClpX protein antigen was introduced to BALB/c mice through a mucosal route, and protection against nasopharyngeal colonization and lethal infection caused by different S. pneumoniae serotypes was successfully elicited. Our findings suggest that ClpX is a potential candidate antigen that could be incorporated in pneumococcal protein vaccines.
Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, People's Republic of China.
Wen
W
Zhong
Wenchun
W
Xu
Hong
H
Wang
Yuanshuai
Y
Huang
Ju
J
Cao
Yi
Y
Gong
Xiuyu
X
Xu
Xun
X
Min
Yanqing
Y
Zhang
Jie
J
Dong
Yibing
Y
Yin
Xuemei
X
Zhang
D000281:Administration, Intranasal; D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000097:blood; D002364:Caseins / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D056738:Cross Protection / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D051379:Mice; D008807:Mice, Inbred BALB C; D010447:Peptide Hydrolases / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D011008:Pneumococcal Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D020545:Respiratory Mucosa / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000378:metabolism
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D002364:Caseins; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; D010447:Peptide Hydrolases