Characterization of immune responses induced by intramuscular vaccination with DNA vaccines encoding measles virus hemagglutinin and/or fusion proteins.
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.
Song
Man Ki
MK
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, 21201, USA.
Vindurampulle
Christofer J
CJ
Capozzo
Alejandra V E
AV
Ulmer
Jeffrey
J
Polo
John M
JM
Pasetti
Marcela F
MF
Barry
Eileen M
EM
Levine
Myron M
MM
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*
D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; D007074:Immunoglobulin G; D008458:Measles Vaccine; D019444:Vaccines, DNA; D014760:Viral Fusion Proteins; D007371:Interferon-gamma