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Prompt and Robust Humoral Immunity Elicited by a Conjugated Chimeric Malaria Antigen with a Truncated Flagellin
Guo, Fangxia1,2; Liu, Yongdong1; Zhang, Chun1; Wang, Qi1,2; Wang, Lianyan1; Gao, Yuhui3; Bi, Jingxiu4; Wang, Heng3; Su, Zhiguo1
AbstractAs one of the pathogen-associated molecular patterns (PAMPs), flagellin is recently utilized as a potent adjuvant for many subunit vaccines. In this study, a truncated flagellin (tFL) with deletion of the hypervariable regions was adopted as a carrier-adjuvant by chemical conjugation with a chimeric malaria antigen M.RCAg-1 (M312) via a heterobifunctional polyethylene glycol (PEG) linker. After booster immunization in mice without any extra adjuvants, the M312-PEG-tFL conjugates elicited M312-specific antibody titers 100-1000 times higher than M312 and 10-100 times higher than the physical mixture of M312 and tFL. The elicited specific antibodies could recognize the native parasites, and the immunofluorescence assay (IFA) titer was 2100 for M312-P5k-tFL, which was about 7 times higher than M312. Furthermore, the IFA titers of the conjugates were comparable to the positive control of complete Freund's adjuvant (CFA). Compared to M312, the M312-PEG-tFL conjugates enhanced the proliferation index, lymphocyte activation, and memory T-cell generation. IgG subclasses of sera and cytokines analysis of splenocytes showed that conjugation with tFL could slightly trigger the Th1 polarization, while the antigen alone predominantly induced a Th2-biased immune response. Furthermore, a more-efficient innate immune response was provoked by the M312-PEG-tFL conjugates, as determined by the detection of antigen-specific TNF-alpha secretion by splenocytes. Our results indicated that tFL mainly retained the function as an agonist of TLR5. Conjugation of antigen to tFL could induce strong humoral and moderate cellular immune responses. Thus, conjugation of antigen to tFL as a potent carrier-adjuvant is an effective strategy for developing a promising protein-based vaccine.
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine ; Physical Sciences
Indexed BySCI
WOS Research AreaBiochemistry & Molecular Biology ; Chemistry
WOS SubjectBiochemical Research Methods ; Biochemistry & Molecular Biology ; Chemistry, Multidisciplinary ; Chemistry, Organic
Funding OrganizationNational Science and Technology Major Project of "National Key Program on Drug Innovation"(2013ZX09102-043) ; National Natural Science Foundation of China(21576267) ; Beijing National Science Foundation(2162041) ; Major State Basic Research Development Program of China(2013CB733604)
WOS IDWOS:000428356300019
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Document Type期刊论文
Affiliation1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Chinese Acad Med Sci, Inst Basic Med Sci, Peking Union Med Coll, Mol Parasitol Lab, Beijing 100005, Peoples R China
4.Univ Adelaide, Sch Chem Engn, Adelaide, SA 5005, Australia
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Guo, Fangxia,Liu, Yongdong,Zhang, Chun,et al. Prompt and Robust Humoral Immunity Elicited by a Conjugated Chimeric Malaria Antigen with a Truncated Flagellin[J]. BIOCONJUGATE CHEMISTRY,2018,29(3):761-770.
APA Guo, Fangxia.,Liu, Yongdong.,Zhang, Chun.,Wang, Qi.,Wang, Lianyan.,...&Su, Zhiguo.(2018).Prompt and Robust Humoral Immunity Elicited by a Conjugated Chimeric Malaria Antigen with a Truncated Flagellin.BIOCONJUGATE CHEMISTRY,29(3),761-770.
MLA Guo, Fangxia,et al."Prompt and Robust Humoral Immunity Elicited by a Conjugated Chimeric Malaria Antigen with a Truncated Flagellin".BIOCONJUGATE CHEMISTRY 29.3(2018):761-770.
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