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Clinical and Vaccine Immunology, August 2008, p. 1214-1221, Vol. 15, No. 8
1071-412X/08/$08.00+0     doi:10.1128/CVI.00120-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Use of Vaxfectin Adjuvant with DNA Vaccine Encoding the Measles Virus Hemagglutinin and Fusion Proteins Protects Juvenile and Infant Rhesus Macaques against Measles Virus{triangledown}

Chien-Hsiung Pan,1 Gretchen S. Jimenez,4 Nitya Nair,1 Qun Wei,4 Robert J. Adams,2 Fernando P. Polack,1,3 Alain Rolland,4 Adrián Vilalta,4 and Diane E. Griffin1*

W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205,1 Departments of Molecular and Comparative Pathology,2 Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21218,3 Vical Incorporated, San Diego, California 921214

Received 4 April 2008/ Returned for modification 6 May 2008/ Accepted 21 May 2008

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 µg 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.

* Corresponding author. Mailing address: W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Baltimore, MD 21205. Phone: (410) 955-3459. Fax: (410) 955-0105. E-mail: dgriffin{at}jhsph.edu

{triangledown} Published ahead of print on 4 June 2008.

Clinical and Vaccine Immunology, August 2008, p. 1214-1221, Vol. 15, No. 8
1071-412X/08/$08.00+0     doi:10.1128/CVI.00120-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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