Unknown

Dataset Information

0

The Immunodominance Change and Protection of CD4+ T-Cell Responses Elicited by an Envelope Protein Domain III-Based Tetravalent Dengue Vaccine in Mice.


ABSTRACT: Dengue is the leading cause of mosquito-borne viral infections and no vaccine is available now. Envelope protein domain III (ED3) is the major target for the binding of dengue virus neutralizing antibodies; however, the ED3-specifc T-cell response is less well understood. To investigate the T-cell responses to four serotypes of dengue virus (DENV-1 to 4), we immunized mice using either a tetravalent ED3-based DNA or protein vaccine, or combined both as a DNA prime-protein boost strategy (prime-boost). A significant serotype-dependent IFN-? or IL-4 response was observed in mice immunized with either the DNA or protein vaccine. The IFN-? response was dominant to DENV-1 to 3, whereas the IL-4 response was dominant to DENV-4. Although the similar IgG titers for the four serotypes were observed in mice immunized with the tetravalent vaccines, the neutralizing antibody titers varied and followed the order of 2 = 3>1>4. Interestingly, the lower IFN-? response to DENV-4 is attributable to the immunodominance change between two CD4+ T-cell epitopes; one T-cell epitope located at E349-363 of DENV-1 to 3 was more immunogenic than the DENV-4 epitope E313-327. Despite DENV-4 specific IFN-? responses were suppressed by immunodominance change, either DENV-4-specific IFN-? or neutralizing antibody responses were still recalled after DENV-4 challenge and contributed to virus clearance. Immunization with the prime-boost elicited both IFN-? and neutralizing antibody responses and provided better protection than either DNA or protein immunization. Our findings shed light on how ED3-based tetravalent dengue vaccines sharpen host CD4 T-cell responses and contribute to protection against dengue virus.

SUBMITTER: Chen HW 

PROVIDER: S-EPMC4695087 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

altmetric image

Publications

The Immunodominance Change and Protection of CD4+ T-Cell Responses Elicited by an Envelope Protein Domain III-Based Tetravalent Dengue Vaccine in Mice.

Chen Hsin-Wei HW   Hu Hui-Mei HM   Wu Szu-Hsien SH   Chiang Chen-Yi CY   Hsiao Yu-Ju YJ   Wu Chia-Kai CK   Hsieh Chun-Hsiang CH   Chung Han-Hsuan HH   Chong Pele P   Leng Chih-Hsiang CH   Pan Chien-Hsiung CH  

PloS one 20151229 12


Dengue is the leading cause of mosquito-borne viral infections and no vaccine is available now. Envelope protein domain III (ED3) is the major target for the binding of dengue virus neutralizing antibodies; however, the ED3-specifc T-cell response is less well understood. To investigate the T-cell responses to four serotypes of dengue virus (DENV-1 to 4), we immunized mice using either a tetravalent ED3-based DNA or protein vaccine, or combined both as a DNA prime-protein boost strategy (prime-b  ...[more]

Similar Datasets

| S-EPMC5686733 | biostudies-literature
| S-EPMC6295631 | biostudies-literature
| S-EPMC8413300 | biostudies-literature
| S-EPMC6576073 | biostudies-literature
| S-EPMC6956717 | biostudies-literature
| S-EPMC7325620 | biostudies-literature
| S-EPMC5584992 | biostudies-literature
| S-EPMC5805027 | biostudies-literature
| S-EPMC5774828 | biostudies-literature
| S-EPMC4965760 | biostudies-literature