title: Characterization of immune responses induced by intramuscular vaccination with DNA vaccines encoding measles virus hemagglutinin and/or fusion proteins.
abstract: 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.
authors: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, 21201, USA.
authors: Man Ki
authors: MK
authors: Song
authors: Christofer J
authors: CJ
authors: Vindurampulle
authors: Alejandra V E
authors: AV
authors: Capozzo
authors: Jeffrey
authors: J
authors: Ulmer
authors: John M
authors: JM
authors: Polo
authors: Marcela F
authors: MF
authors: Pasetti
authors: Eileen M
authors: EM
authors: Barry
authors: Myron M
authors: MM
authors: Levine
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000915:Antibody Affinity; D004353:Drug Evaluation, Preclinical; D005260:Female; D006389:Hemagglutinins, Viral / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000096:biosynthesis; D008457:Measles / Q000276:immunology*; D008458:Measles Vaccine / Q000008:administration & dosage / Q000276:immunology*; D008459:Measles virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology; D014760:Viral Fusion Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; D007074:Immunoglobulin G; D008458:Measles Vaccine; D019444:Vaccines, DNA; D014760:Viral Fusion Proteins; D007371:Interferon-gamma