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

Doris Apt*, Kanakatte Raviprakash, Alice Brinkman, Andrey Semyonov, Shumin Yang, Craig Skinner, Lori Diehl, Richard Lyons, Kevin Porter, Juha Punnonen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

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. The neutralizing antibody titers for some of these antigens could be further improved by extending the sequences to express full-length pre-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.

Original languageEnglish
Pages (from-to)335-344
Number of pages10
JournalVaccine
Volume24
Issue number3
DOIs
StatePublished - 16 Jan 2006
Externally publishedYes

Keywords

  • Antigen
  • Cross-neutralizing antibodies
  • DNA shuffling
  • Dengue virus
  • Multivalent antigen
  • Tetravalent

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