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Journal of Virology, August 2005, p. 9854-9861, Vol. 79, No. 15
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.15.9854-9861.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Characterization of Immune Responses Induced by Intramuscular Vaccination with DNA Vaccines Encoding Measles Virus Hemagglutinin and/or Fusion Proteins

Man Ki Song,1,3 Christofer J. Vindurampulle,1 Alejandra V. E. Capozzo,1 Jeffrey Ulmer,2 John M. Polo,2 Marcela F. Pasetti,1 Eileen M. Barry,1 and Myron M. Levine1*

Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland,1 Chiron Vaccines, Emeryville, California,2 International Vaccine Institute, Seoul, Korea3

Received 22 December 2004/ Accepted 18 April 2005

Measles virus (MV) hemagglutinin (MV-H) and fusion (MV-F) proteins induce plaque reduction neutralizing (PRN) antibodies and cell-mediated immune responses that protect against clinical measles. DNA vaccines that encode MV-H and MV-F are being investigated as a new generation of measles vaccine to protect infants too young to receive currently licensed attenuated measles vaccines. However, it is unclear whether DNA vaccines encoding both MV-H and MV-F act synergistically to induce stronger immunity than immunization with plasmids encoding MV-H or MV-F alone. To address this question, we generated Sindbis virus-based pSINCP DNA vaccines that encode either MV-H or MV-F alone or bicistronic or fusion system vectors that encode both MV-H and MV-F (to mimic MV infection where both MV-H and MV-F proteins are expressed by the same mammalian cell). Mice immunized with DNA vaccine encoding MV-H alone developed significantly greater PRN titers than mice immunized with bicistronic constructs. Interestingly, the presence of MV-F in the bicistronic constructs stimulated serum MV-specific immunoglobulin G of reduced avidity. By contrast, mice immunized with bicistronic constructs induced equivalent or higher levels of MV-specific gamma interferon responses than mice immunized with DNA vaccine encoding MV-H alone. These data will help guide the design of DNA-based MV vaccines to be used early in life in a heterologous prime-boost strategy.


* Corresponding author. Mailing address: Center for Vaccine Development, University of Maryland School of Medicine, 685 W. Baltimore St., Rm. 480, Baltimore, MD 21201. Phone: (410) 706-7588. Fax: (410) 706-6205. E-mail: mlevine{at}medicine.umaryland.edu.


Journal of Virology, August 2005, p. 9854-9861, Vol. 79, No. 15
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.15.9854-9861.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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