Advanced in Research Dengue Virus 3'UTRΔ30 Series Vaccines

doi:10.13523/j.cb.20190312

China Biotechnology

2019, Vol. 39

Issue (3): 97-104 DOI: 10.13523/j.cb.20190312

Advanced in Research Dengue Virus 3'UTRΔ30 Series Vaccines

Jia-yue XU,Zi-qian LI,Ge ZHANG(

)

School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou 510006, China

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Abstract

Diseases such as dengue fever caused by denugue virus lead to considerable economic, medical and social burdens every year, which seriously threaten the health of human life. Among the various dengue virus vaccines currently under study, the 3'UTRΔ30 series of live attenuated vaccines prepared by reverse genetics have shown good protection in clinical trials because of their good immunogenicity, high titer and low cost. As a consequence, research on this kind of vaccine advances fast. The 3'UTRΔ30 quadruple vaccine, one of the most promising dengue attenuated inactivated vaccines today, which can produce balanced immune protection against the four serotypes of dengue virus, is in phase III clinical trials, showing strong efficacy and few adverse reactions. It is expected to be on the market after the end of the follow-up period. In order to gain a deeper understanding of the 3'UTRΔ30 series vaccines, the origin, preparation methods and clinical research are mainly focused on.

Key words： Dengue virus 3'UTRΔ30 vaccine Preparation Clinical research

Received: 20 September 2018 Published: 12 April 2019

ZTFLH:

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Corresponding Authors: Ge ZHANG E-mail: zhangge@mail.sysu.edu.cn

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Cite this article:

Jia-yue XU,Zi-qian LI,Ge ZHANG. Advanced in Research Dengue Virus 3'UTRΔ30 Series Vaccines. China Biotechnology, 2019, 39(3): 97-104.

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https://manu60.magtech.com.cn/biotech/10.13523/j.cb.20190312 OR https://manu60.magtech.com.cn/biotech/Y2019/V39/I3/97

Fig.1 The gene structure of DENV^[1]

Fig.2 The partial structure of rDENV4Δ30 and rDENV1Δ30^[9]

试验疫苗	时间	试验分期	试验地点	试验对象	接种方式&剂量	参考文献
rDENV4Δ30	1996	临床前	美国 NIAID	恒河猴	单次免疫;s.c.¹); 剂量(1×10⁵ PFU)	[11]
	2001	临床I期	美国 CIR	健康志愿者20人	单次免疫;s.c.;剂量(1×10⁵ PFU/0.5ml)	[12][14]
	2005	临床II期	美国 NIAID	健康志愿者5人	单次免疫;s.c.;剂量递减(1×10³ PFU,1×102 PFU,10 PFU)	[13]
rDENV4Δ30-200,201	2008	临床I期	美国 NIAID	健康志愿者20人	单次免疫;s.c.;剂量(1×10⁵ PFU/0.5ml)	[15]
rDENV4Δ30-4995	2009	临床I期	美国 NIAID	健康志愿者20人	单次免疫;s.c.;剂量(1×10⁵ PFU/0.5ml)	[16]
rDENV1Δ30	2003	临床前	美国 NIAID	恒河猴	单次免疫;s.c.;剂量(1×10⁵ PFU/0.5ml)	[17]
	2006	临床I期	美国 NIAID	健康志愿者28人	单次免疫;s.c.;剂量(1×10³ PFU/0.5ml)	[18]
rDENV2/4Δ30	2003	临床前	美国 NIAID	小鼠,恒河猴等	单次免疫;s.c.;剂量(小鼠1×104 PFU,猴1×10⁵ PFU)	[19]
	2006	临床I期	美国 NIAID	健康志愿者20人	单次免疫;s.c.;剂量(1×10³ PFU/0.5ml)	[21]
rDENV3/4Δ30	2004	临床前	美国 NIAID	小鼠,恒河猴等	单次免疫;s.c.;剂量(小鼠1×10⁴ PFU,猴1×10⁵ PFU)	[20]
rDENV3Δ30/31	2011	临床I期	美国 NIAID	健康志愿者20人	单次免疫;s.c.;剂量(1×10³ PFU)	[22]
rDENV3-3'D4Δ30	2011	临床I期	美国 NIAID	健康志愿者20人	单次免疫;s.c.;剂量(1×10³ PFU)	[22]
TV001TV004	2013	临床I期	美国 NIAID	每种疫苗健康志愿者28人,共112人	单次免疫;s.c.;剂量(1×10³ PFU/0.5ml)	[23]
TV003、TV005	2015	临床I期	美国 NIAID	健康志愿者共168人	6个月后加强免疫;s.c.;剂量(1×10³ PFU)	[24]
TV003	2016	临床I期	美国 NIAID	健康志愿者48人	12个月后加强免疫;s.c.;剂量(1×10³ PFU)	[25]
	2016	临床II期	美国 NIAID	健康志愿者48人	单次免疫;s.c.;剂量(1×10³ PFU)	[26]
	2016 -	临床II期	泰国, 孟加拉国		单剂量	[25],[28]
	2016年 2月 -	临床III期	巴西		单剂量,五年随访	[25], [27], [28]

Table 1 The research status of Dengue Virus Vaccine: 3'UTRΔ30

Fig.3 The preparation process of rDENV2/4△30^[19]

Table 2 The composition of 3'UTRΔ30 quadruple vaccine TV001TV004

Table 3 The comparison between TV003 and CYD-TDV^TM


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