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本文引用的文献

1
rDEN4delta30, a live attenuated dengue virus type 4 vaccine candidate, is safe, immunogenic, and highly infectious in healthy adult volunteers.rDEN4delta30是一种4型登革热减毒活疫苗候选株，在健康成年志愿者中安全、具有免疫原性且传染性很强。
J Infect Dis. 2005 Mar 1;191(5):710-8. doi: 10.1086/427780. Epub 2005 Jan 27.
2
Genetically modified, live attenuated dengue virus type 3 vaccine candidates.基因改造的3型登革热病毒减毒活疫苗候选株。
Am J Trop Med Hyg. 2004 Dec;71(6):811-21.
3
Vaccine candidates derived from a novel infectious cDNA clone of an American genotype dengue virus type 2.源自美国基因型2型登革病毒新型感染性cDNA克隆的候选疫苗。
BMC Infect Dis. 2004 Oct 4;4:39. doi: 10.1186/1471-2334-4-39.
4
Introduction of mutations into the non-structural genes or 3' untranslated region of an attenuated dengue virus type 4 vaccine candidate further decreases replication in rhesus monkeys while retaining protective immunity.将突变引入减毒登革4型候选疫苗的非结构基因或3'非翻译区，可进一步降低其在恒河猴体内的复制，同时保留保护性免疫。
Vaccine. 2004 Sep 3;22(25-26):3440-8. doi: 10.1016/j.vaccine.2004.02.031.
5
Arguments for live flavivirus vaccines.
Lancet. 2004;364(9433):499-500. doi: 10.1016/S0140-6736(04)16801-3.
6
Safety and efficacy of chimeric yellow Fever-dengue virus tetravalent vaccine formulations in nonhuman primates.嵌合黄热病-登革热病毒四价疫苗制剂在非人灵长类动物中的安全性和有效性。
J Virol. 2004 May;78(9):4761-75. doi: 10.1128/jvi.78.9.4761-4775.2004.
7
Research on dengue during World War II.第二次世界大战期间关于登革热的研究。
Am J Trop Med Hyg. 1952 Jan;1(1):30-50. doi: 10.4269/ajtmh.1952.1.30.
8
Safety and immunogenicity of a three dose regimen of two tetravalent live-attenuated dengue vaccines in five- to twelve-year-old Thai children.两种四价减毒活登革热疫苗三剂次接种方案在5至12岁泰国儿童中的安全性和免疫原性
Pediatr Infect Dis J. 2004 Feb;23(2):99-109. doi: 10.1097/01.inf.0000109289.55856.27.
9
Phase I trial of 16 formulations of a tetravalent live-attenuated dengue vaccine.四价减毒活登革热疫苗16种配方的I期试验。
Am J Trop Med Hyg. 2003 Dec;69(6 Suppl):48-60. doi: 10.4269/ajtmh.2003.69.48.
10
Vaccination of human volunteers with monovalent and tetravalent live-attenuated dengue vaccine candidates.用单价和四价减毒活登革热候选疫苗对人类志愿者进行接种。
Am J Trop Med Hyg. 2003 Dec;69(6 Suppl):24-31. doi: 10.4269/ajtmh.2003.69.6_suppl.0690024.

重组减毒活四价登革病毒疫苗制剂可在恒河猴体内诱导针对四种血清型中每一种的平衡、广泛且具有保护性的中和抗体反应。

Recombinant, live-attenuated tetravalent dengue virus vaccine formulations induce a balanced, broad, and protective neutralizing antibody response against each of the four serotypes in rhesus monkeys.

作者信息

Blaney Joseph E, Matro Jennifer M, Murphy Brian R, Whitehead Stephen S

机构信息

Laboratory of Infectious Diseases, NIH, NIAID, LID Twinbrook III, Room 3W-13, 12735 Twinbrook Parkway, MSC 8133, Bethesda, MD 20892-8133, USA.

出版信息

J Virol. 2005 May;79(9):5516-28. doi: 10.1128/JVI.79.9.5516-5528.2005.

DOI:10.1128/JVI.79.9.5516-5528.2005
PMID:15827166
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1082773/
Abstract

Three tetravalent vaccine (TV) formulations of previously described monovalent dengue (DEN) virus vaccine candidates were compared to a tetravalent formulation of wild-type DEN viruses (T-wt) for replication in SCID mice transplanted with human liver cells (SCID-HuH-7) or for replication and immunogenicity in rhesus monkeys. TV-1 consists of recombinant DEN1, -2, -3, and -4, each with a 30-nucleotide deletion in the 3' untranslated region (Delta30). TV-2 consists of rDEN1Delta30, rDEN4Delta30, and two antigenic chimeric viruses, rDEN2/4Delta30 and rDEN3/4Delta30, both also bearing the Delta30 mutation. TV-3 consists of rDEN1Delta30, rDEN2Delta30, rDEN4Delta30, and a 10-fold higher dose of rDEN3/4Delta30. TV-1 and TV-2 were attenuated in SCID-HuH-7 mice with minimal interference in replication among the virus components. TV-1, -2, and -3 were attenuated in rhesus monkeys as measured by duration and peak of viremia. Each monkey immunized with TV-1 and TV-3 seroconverted to the four DEN components by day 28 with neutralization titers ranging from 1:52 to 1:273 and 1:59 to 1:144 for TV-1 and TV-3, respectively. TV-2 induced low antibody titers to DEN2 and DEN3, but a booster immunization after 4 months increased the neutralizing antibody titers to greater than 1:100 against each serotype and elicited broad neutralizing activity against 19 of 20 DEN subtypes. A single dose of TV-2 induced protection against wild-type DEN1, DEN3, and DEN4 challenge, but not DEN2. However, two doses of TV-2 or TV-3 induced protection against DEN2 challenge. Two tetravalent formulations, TV-2 and TV-3, possess properties of a successful DEN vaccine and can be considered for evaluation in clinical trials.

摘要

将之前描述的单价登革热（DEN）病毒候选疫苗的三种四价疫苗（TV）配方与野生型DEN病毒的四价配方（T-wt）进行比较，以研究它们在移植了人肝细胞的SCID小鼠（SCID-HuH-7）中的复制情况，以及在恒河猴中的复制和免疫原性。TV-1由重组DEN1、-2、-3和-4组成，每种在3'非翻译区均有30个核苷酸的缺失（Delta30）。TV-2由rDEN1Delta30、rDEN4Delta30以及两种抗原嵌合病毒rDEN2/4Delta30和rDEN3/4Delta30组成，这两种嵌合病毒也都带有Delta30突变。TV-3由rDEN1Delta30、rDEN2Delta30、rDEN4Delta30以及剂量高10倍的rDEN3/4Delta30组成。TV-1和TV-2在SCID-HuH-7小鼠中减毒，病毒成分之间的复制干扰最小。通过病毒血症的持续时间和峰值测量，TV-1、-2和-3在恒河猴中均减毒。用TV-1和TV-3免疫的每只猴子在第28天时均对四种DEN成分产生血清转化，TV-1和TV-3的中和效价分别为1:52至1:273和1:59至1:144。TV-2诱导的针对DEN2和DEN3的抗体效价较低，但4个月后的加强免疫使针对每种血清型的中和抗体效价提高到大于1:100，并引发了针对20种DEN亚型中19种的广泛中和活性。单剂量的TV-2可诱导对野生型DEN1、DEN3和DEN4攻击的保护作用，但对DEN2无效。然而，两剂量的TV-2或TV-3可诱导对DEN2攻击的保护作用。两种四价配方TV-2和TV-3具有成功的DEN疫苗的特性，可考虑用于临床试验评估。