Tetravalent neutralizing antibody response against four dengue serotypes by a single chimeric dengue envelope antigen

被引：54

作者：

Apt, D

Raviprakash, K

Brinkman, A

Semyonov, A

Yang, SM

Skinner, C

Diehl, L

Lyons, R

Porter, K

Punnonen, J

机构：

[1] Maxygen Inc, Human Therapeut, Redwood City, CA 94063 USA

[2] USN, Med Res Ctr, Viral Dis Dept, Silver Spring, MD 20910 USA

[3] Univ New Mexico, Hlth Sci Ctr, Dept Internal Med, Albuquerque, NM 87131 USA

来源：

VACCINE | 2006年 / 24卷 / 03期

关键词：

dengue virus; antigen; tetravalent; multivalent antigen; DNA shuffling; cross-neutralizing antibodies;

D O I：

10.1016/j.vaccine.2005.07.100

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

We employed DNA shuffling and screening technologies to develop a single recombinant dengue envelope (E) antigen capable of inducing neutralizing antibodies against all four antigenically distinct dengue serotypes. By DNA shuffling of codon-optimized dengue 1-4 E genes, we created a panel of novel chimeric clones expressing C-terminal truncated E antigens that combined epitopes from all four dengue serotypes. DNA vaccines encoding these novel chimeras induced multivalent T cell and neutralizing antibody responses against all four dengue serotypes in mice. By contrast, a mixture of four unshuffled, parental DNA vaccines failed to produce tetravalent neutralizing antibodies in mice. length neutralizing antibody titers for some of these antigens could be further improved by extending the sequences to express full membrane and envelope proteins. The chimeric antigens also protected mice against a lethal dengue-2 virus challenge. These data demonstrate that DNA shuffling and associated screening can lead to the selection of multi-epitope antigens against closely related dengue virus serotypes and suggest a broad utility for these technologies in optimizing vaccine antigens. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：335 / 344

页数：10

共 38 条

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