Use of Vaxfectin adjuvant with DNA vaccine encoding the measles virus hemagglutinin and fusion proteins protects juvenile and infant rhesus macaques against measles virus

Clin Vaccine Immunol. 2008 Aug;15(8):1214-21. doi: 10.1128/CVI.00120-08. Epub 2008 Jun 4.

Abstract

A measles virus vaccine for infants under 6 months of age would help control measles. DNA vaccines hold promise, but none has provided full protection from challenge. Codon-optimized plasmid DNAs encoding the measles virus hemagglutinin and fusion glycoproteins were formulated with the cationic lipid-based adjuvant Vaxfectin. In mice, antibody and gamma interferon (IFN-gamma) production were increased by two- to threefold. In macaques, juveniles vaccinated at 0 and 28 days with 500 microg of DNA intradermally or with 1 mg intramuscularly developed sustained neutralizing antibody and H- and F-specific IFN-gamma responses. Infant monkeys developed sustained neutralizing antibody and T cells secreting IFN-gamma and interleukin-4. Twelve to 15 months after vaccination, vaccinated monkeys were protected from an intratracheal challenge: viremia was undetectable by cocultivation and rashes did not appear, while two naïve monkeys developed viremia and rashes. The use of Vaxfectin-formulated DNA is a promising approach to the development of a measles vaccine for young infants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Antibodies, Viral / blood
  • Female
  • Hemagglutinins, Viral / genetics
  • Hemagglutinins, Viral / immunology*
  • Humans
  • Interferon-gamma / metabolism
  • Macaca mulatta
  • Measles / immunology
  • Measles / prevention & control*
  • Measles Vaccine / administration & dosage*
  • Measles Vaccine / genetics
  • Measles Vaccine / immunology
  • Measles virus / immunology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Neutralization Tests
  • Phosphatidylethanolamines / administration & dosage*
  • Phosphatidylethanolamines / immunology
  • Sequence Analysis, DNA
  • T-Lymphocytes / immunology
  • Vaccination
  • Vaccines, DNA / administration & dosage*
  • Vaccines, DNA / immunology
  • Viral Fusion Proteins / genetics
  • Viral Fusion Proteins / immunology*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Hemagglutinins, Viral
  • Measles Vaccine
  • Phosphatidylethanolamines
  • Vaccines, DNA
  • Viral Fusion Proteins
  • hemagglutinin protein G, measles virus
  • vaxfectin
  • Interferon-gamma

Associated data

  • GENBANK/EU723762
  • GENBANK/EU723763