In vivo electroporation in DNA-VLP prime-boost preferentially enhances HIV-1 envelope-specific IgG2a, neutralizing antibody and CD8 T cell

doi:10.1016/j.vaccine.2017.03.006

	In vivo electroporation in DNA-VLP prime-boost preferentially enhances HIV-1 envelope-specific IgG2a, neutralizing antibody and CD8 T cell
	Huang, Xun 1; Zhu, Qianqian1,2 ; Huang, Xiaoxing 3; Yang, Lifei 1,4; Song, Yufeng 1; Zhu, Ping 3; Zhou, Paul1,2
	2017-04-11
发表期刊	VACCINE (IF:4.5[JCR-2023],3.7[5-Year])
ISSN	0264-410X
卷号	35 期号:16 页码:2042-2051
发表状态	已发表
DOI	10.1016/j.vaccine.2017.03.006
摘要	Although in vivo electroporation (EP) has been utilized to improve immunogenicity in DNA vaccines alone or in prime-boost regimens with both proteins and viral-vectors, no studies on in vivo EP in DNA-VLP prime-boost regimens against HIV-1 have been reported. Previously we developed stably transfected Drosophila S2 clones to produce HIV-1 virus-like particles (VLP) and demonstrated that priming mice twice with DNA plasmids encoding HIV-1 gp120 and gag and boosting twice with HIV-1 VLP (i.e. DDVV immunization) elicited both envelope-specific antibody and envelope and gag-specific CD8 T cell responses. However, the potency and the breadth of immunogenicity still need to be improved. In this study we tested the effect of in vivo EP during DNA priming on immunogenicity of this DNA-VLP prime-boost regimen. Here we report that although both DDVV and DDVV + EP elicited gp120-specific ELISA-binding antibody responses, average EC50 values of gp120-specific ELISA-binding total IgG, IgG2a, but not IgG1, antibody responses were significantly higher in DDVV + EP than in DDVV. Moreover, while DDVV elicited neutralizing antibody responses against autologous, but not other five, strains tested, DDVV + EP not only elicited significantly higher anti-autologous neutralizing antibody responses, but also cross-neutralizes four of five other HIV-1 strains tested, including two tier 2 strains. Finally, although CD4 and CD8 T cells from both DDVV and DDVV + EP immunizations secreted IFN-gamma, IL-2, TNF-alpha upon HIV-1 envelope peptide stimulation, average HIV-1 envelope-specific CD8 T cells that secreted IFN-gamma, IL-2 and/or TNF-alpha were significantly higher in DDVV + EP than in DDVV. Thus we conclude that DDVV + EP immunization preferentially increases HIV-1 envelope-specific T(H)1 cytoldne-mediated IgG2a responses and significantly enhances the potency and the breadth of neutralizing antibody responses including tier 2 viruses. Further study on this heterologous regimen in large animals is warranted. (C) 2017 Elsevier Ltd. All rights reserved.
关键词	Heterologous prime-boost vaccination In vivo electroporation HIV-1 IgG subclasses Neutralizing antibody T cell responses
收录类别	SCI
语种	英语
资助项目	National Laboratory of Biomacromolecules[2016KF02]
WOS研究方向	Immunology ; Research & Experimental Medicine
WOS类目	Immunology ; Medicine, Research & Experimental
WOS记录号	WOS:000399858900008
出版者	ELSEVIER SCI LTD
WOS关键词	IMMUNODEFICIENCY-VIRUS TYPE-1 ; HIGHLY PATHOGENIC SIV ; IMMUNE-RESPONSES ; IMPROVES PROTECTION ; CO-IMMUNIZATION ; RHESUS MACAQUES ; VACCINE ; PROTEIN ; ENV ; IMMUNOGENICITY
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1416
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_周保罗组生命科学与技术学院_硕士生
通讯作者	Zhou, Paul
作者单位	1.Chinese Acad Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Unit Antiviral Immun & Genet Therapy, Shanghai, Peoples R China 2.Shanghai Tech Univ, Shanghai, Peoples R China 3.Chinese Acad Sci, Inst Biophys, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing, Peoples R China 4.Univ Washington, Dept Pharmaceut, 3000 Western Ave, Seattle, WA 98121 USA
通讯作者单位	上海科技大学
推荐引用方式 GB/T 7714	Huang, Xun,Zhu, Qianqian,Huang, Xiaoxing,et al. In vivo electroporation in DNA-VLP prime-boost preferentially enhances HIV-1 envelope-specific IgG2a, neutralizing antibody and CD8 T cell[J]. VACCINE,2017,35(16):2042-2051.
APA	Huang, Xun.,Zhu, Qianqian.,Huang, Xiaoxing.,Yang, Lifei.,Song, Yufeng.,...&Zhou, Paul.(2017).In vivo electroporation in DNA-VLP prime-boost preferentially enhances HIV-1 envelope-specific IgG2a, neutralizing antibody and CD8 T cell.VACCINE,35(16),2042-2051.
MLA	Huang, Xun,et al."In vivo electroporation in DNA-VLP prime-boost preferentially enhances HIV-1 envelope-specific IgG2a, neutralizing antibody and CD8 T cell".VACCINE 35.16(2017):2042-2051.