当前位置： SCI文献检索 > VACCINE期刊下所有文献 > 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.

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.

Abstract：

:A dengue virus vaccine candidate, rDEN4Delta30, has been previously reported to be safe and immunogenic in humans, but a subset of vaccinees developed asymptomatic rash, elevation of liver enzymes and/or mild neutropenia. In the current study, mutations that had previously been shown to reduce replication of DEN4 virus in suckling mice and/or in SCID mice engrafted with human liver cells (SCID-HuH-7 mice) were introduced into rDEN4Delta30 in an attempt to further attenuate this virus. Three of the five resulting modified rDEN4Delta30 viruses showed decreased replication in SCID-HuH-7 mice relative to rDEN4Delta30. Moreover, in rhesus monkeys, two of the modified rDEN4Delta30 viruses showed a decrease in replication relative to rDEN4Delta30 while generating levels of neutralizing antibody similar to rDEN4Delta30 virus. All of the modified rDEN4Delta30 viruses completely protected immunized rhesus monkeys from challenge with wild-type DEN4 virus. Based on their attenuation for both human liver cells and rhesus monkeys, two of the modified rDEN4Delta30 vaccine candidates are currently being prepared for use in clinical trials. The application of these attenuating mutations to flavivirus vaccine development is discussed.

journal_name

Vaccine

journal_title

Vaccine

authors

Hanley KA,Manlucu LR,Manipon GG,Hanson CT,Whitehead SS,Murphy BR,Blaney JE Jr

doi

10.1016/j.vaccine.2004.02.031

subject

Has Abstract

pub_date

2004-09-03 00:00:00

pages

3440-8

issue

25-26

eissn

0264-410X

issn

1873-2518

pii

S0264410X04001975

journal_volume

22

pub_type

杂志文章

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