Intranasal Immunization with Zika Virus Envelope Domain III-Flagellin Fusion Protein Elicits Systemic and Mucosal Immune Responses and Protection against Subcutaneous and Intravaginal Virus Challenges

被引：10

作者：

Chen, Chi-Hsun ^{[1
]}

Chen, Chung-Chu ^{[2
,3
]}

Wang, Wei-Bo ^{[1
]}

Lionel, Vania ^{[1
]}

Liu, Chia-Chyi ^{[4
]}

Huang, Li-Min ^{[5
]}

Wu, Suh-Chin ^{[1
,6
,7
]}

机构：

[1] Natl Tsing Hua Univ, Inst Biotechnol, Hsinchu 30013, Taiwan

[2] MacKay Mem Hosp, Dept Internal Med, Hsinchu 30071, Taiwan

[3] Minghsin Univ Sci & Technol, Teaching Ctr Nat Sci, Hsinchu 30401, Taiwan

[4] Natl Hlth Res Inst, Natl Inst Infect Dis & Vaccinol, Zhunan 35053, Taiwan

[5] Natl Taiwan Univ Hosp, Dept Pediat, Taipei 10041, Taiwan

[6] Natl Tsing Hua Univ, Dept Med Sci, Hsinchu 30013, Taiwan

[7] Adimmune Corp, Taichung 42723, Taiwan

来源：

PHARMACEUTICS | 2022年 / 14卷 / 05期

关键词：

intranasal immunization; Zika virus; domain III; mucosal vaccine; BACTERIAL FLAGELLIN; SEXUAL TRANSMISSION; STRUCTURAL BASIS; DENDRITIC CELLS; MOUSE MODEL; INNATE; RECOGNITION; DENGUE; IL-17;

D O I：

10.3390/pharmaceutics14051014

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Zika virus (ZIKV) infections in humans are mainly transmitted by the mosquito vectors, but human-to-human sexual transmission is also another important route. Developing a ZIKV mucosal vaccine that can elicit both systemic and mucosal immune responses is of particular interest. In this study, we constructed a recombinant ZIKV envelope DIII (ZDIII) protein genetically fused with Salmonella typhimurium flagellin (FliC-ZDIII) as a novel mucosal antigen for intranasal immunization. The results indicated that the FliC-ZDIII fusion proteins formulated with E. coli heat-labile enterotoxin B subunit (LTIIb-B5) adjuvant greatly increased the ZDIII-specific IgG, IgA, and neutralizing titers in sera, and the ZDIII-specific IgA titers in bronchoalveolar lavage and vaginal fluids. Protective immunity was further assessed by subcutaneous and intravaginal ZIKV challenges. The second-generation FliC Delta D3-2ZDIII was shown to result in a reduced titer of anti-FliC IgG antibodies in sera and still retained the same levels of serum IgG, IgA, and neutralizing antibodies and mucosal IgA antibodies without compromising the vaccine antigenicity. Therefore, intranasal immunization with FliC Delta D3-2ZDIII fusion proteins formulated with LTIIb-B5 adjuvant elicited the greatest protective immunity against subcutaneous and intravaginal ZIKV challenges. Our findings indicated that the combination of FliC Delta D3-2ZDIII fusion proteins and LTIIb-B5 adjuvant for intranasal immunization can be used for developing ZIKV mucosal vaccines.

引用

页数：18