Use of Vaxfectin adjuvant with DNA vaccine encoding the measles virus hemagglutinin and fusion proteins protects juvenile and infant rhesus macaques against measles virus.
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.
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205, USA.
Chien-Hsiung
CH
Pan
Gretchen S
GS
Jimenez
Nitya
N
Nair
Qun
Q
Wei
Robert J
RJ
Adams
Fernando P
FP
Polack
Alain
A
Rolland
Adrián
A
Vilalta
Diane E
DE
Griffin
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008253:Macaca mulatta; D008457:Measles / Q000276:immunology / Q000517:prevention & control*; D008458:Measles Vaccine / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D008459:Measles virus / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010714:Phosphatidylethanolamines / Q000008:administration & dosage* / Q000276:immunology; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; D008458:Measles Vaccine; D010714:Phosphatidylethanolamines; D019444:Vaccines, DNA; D014760:Viral Fusion Proteins; C032397:hemagglutinin protein G, measles virus; C460866:vaxfectin; D007371:Interferon-gamma