Enhancement of anti-DIII antibodies by the C3d derivative P28 results in lower viral titers and augments protection in mice

Matthew D. Dunn, Shannan Rossi, Donald M. Carter, Matthew R. Vogt, Erin Mehlhop, Michael S. Diamond, Ted M. Ross

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Antibodies generated against West Nile virus (WNV) during infection are essential for controlling dissemination. Recent studies have demonstrated that epitopes in all three domains of the flavivirus envelope protein (E) are targets for neutralizing antibodies, with determinants in domain III (DIII) eliciting antibodies with strong inhibitory properties. In order to increase the magnitude and quality of the antibody response against the WNV E protein, DNA vaccines with derivatives of the WNV E gene (full length E, truncated E, or DIII region, some in the context of the pre-membrane [prM] gene) were conjugated to the molecular adjuvant P28. The P28 region of the complement protein C3d is the minimum CR2-binding domain necessary for the adjuvant activity of C3d. Delivery of DNA-based vaccines by gene gun and intramuscular routes stimulated production of IgG antibodies against the WNV DIII region of the E protein. With the exception of the vaccine expressing prM/E given intramuscularly, only mice that received DNA vaccines by gene gun produced protective neutralizing antibody titers (FRNT 80titer >1/40). Correspondingly, mice vaccinated by the gene gun route were protected to a greater level from lethal WNV challenge. In general, mice vaccinated with P28-adjuvated vaccines produced higher IgG titers than mice vaccinated with non-adjuvanted vaccines.

Original languageEnglish (US)
Article number95
JournalVirology Journal
Volume7
DOIs
StatePublished - 2010
Externally publishedYes

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West Nile virus
DNA Vaccines
Firearms
Antibodies
Vaccines
Genes
Neutralizing Antibodies
Antibody Formation
Complement C3d
Immunoglobulin G
Membranes
Virus Diseases
Epitopes
Complement System Proteins
Proteins

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Enhancement of anti-DIII antibodies by the C3d derivative P28 results in lower viral titers and augments protection in mice. / Dunn, Matthew D.; Rossi, Shannan; Carter, Donald M.; Vogt, Matthew R.; Mehlhop, Erin; Diamond, Michael S.; Ross, Ted M.

In: Virology Journal, Vol. 7, 95, 2010.

Research output: Contribution to journalArticle

Dunn, Matthew D. ; Rossi, Shannan ; Carter, Donald M. ; Vogt, Matthew R. ; Mehlhop, Erin ; Diamond, Michael S. ; Ross, Ted M. / Enhancement of anti-DIII antibodies by the C3d derivative P28 results in lower viral titers and augments protection in mice. In: Virology Journal. 2010 ; Vol. 7.
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