FbaA- and M protein-based multi-epitope vaccine elicits strong protective immune responses against group A streptococcus in mouse model.
We report the construction of a recombinant multivalent vaccine against group A streptococcus (GAS), designated F7M5. It contains seven predominant epitopes of FbaA identified by phage display technology, five non-tissue cross-reactive M protein fragments expressed on four selected serotypes prevalent in China, a Trojan antigen (TA) and a poly-alanine DR epitope (PADRE). BALB/c mice were immunized subcutaneously with F7M5 formulated with Freund's adjuvant, using recombinant FbaA and M protein in parallel as control. Using enzyme-linked immunosorbent assay (ELISA), mouse immune sera were assayed for IgG titers, IgG subclasses, and binding of F7M5 with M1GAS. Results indicated that the multivalent vaccine was highly immunogenic and elicited a balanced IgG1/IgG2a response. We also tested the reactivity of F7M5 to antistreptolysin O (ASO) antibodies in sera of GAS-infected patients and found a 95.8% positive rate, indicating that the epitopes of the vaccine were widely expressed in the prevalent serotypes of GAS. More importantly, the F7M5 vaccine elicited strong protective immune responses against lethal-dose challenge with a survival rate of 90%, but induced no cross-reactions or pathological lesions in mouse model, suggesting that F7M5 can be further developed as an effective and safe anti-GAS vaccine.
Department of Immunology, Basic Medical College, Hebei Medical University, Shijiazhuang 050017, China.
Cuiqing
C
Ma
Department of Immunology, Basic Medical College, Hebei Medical University, Shijiazhuang 050017, China.
Zheng
Z
Liu
Department of Immunology, Basic Medical College, Hebei Medical University, Shijiazhuang 050017, China.
Wenjian
W
Li
Department of Immunology, Basic Medical College, Hebei Medical University, Shijiazhuang 050017, China.
Xuesong
X
Qian
Third Hospital of Hebei Medical University, Shijiazhuang 050000, China.
Song
S
Zhang
Department of Immunology, Basic Medical College, Hebei Medical University, Shijiazhuang 050017, China.
Xue
X
Gao
Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China. Electronic address: shibojiang@fudan.edu.cn.
Shibo
S
Jiang
Department of Immunology, Basic Medical College, Hebei Medical University, Shijiazhuang 050017, China. Electronic address: weilin501@163.com.
Lin
L
Wei
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D002681:China; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D008297:Male; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013290:Streptococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D000939:Epitopes; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D022541:Streptococcal Vaccines; D014614:Vaccines, Synthetic
Epitope; FbaA; Group A streptococcus (GAS); M protein; Vaccine