Construction and characterization of recombinant vaccinia viruses co-expressing a respiratory syncytial virus protein and a cytokine.
Recombinant vaccinia viruses are well-characterized tools that can be used to define novel approaches to vaccine formulation and delivery. While vector co-expression of immune mediators has enormous potential for optimizing the composition of vaccine-induced immune responses, the impact on antigen expression and vector antigenicity must also be considered. Co-expression of IL-4 increased vaccinia virus vector titres, while IFN-gamma co-expression reduced vaccinia virus replication in BALB/c mice and in C57BL/6 mice infected with some recombinant viruses. Protection against respiratory syncytial virus (RSV) challenge was similar in mice immunized with vaccinia virus expressing RSV G glycoprotein and IFN-gamma, even though the replication efficiency of the vector was diminished. These data demonstrate the ability of vector-expressed cytokine to influence the virulence of the vector and to direct the development of selected immune responses. This suggests that the co-expression of cytokines and other immunomodulators has the potential to improve the safety of vaccine vectors while improving the immunogenicity of vaccine antigens.
Johnson
Teresa R
TR
Departments of Microbiology and Immunology1 and Medicine2, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Fischer
Julie E
JE
Departments of Microbiology and Immunology1 and Medicine2, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Graham
Barney S
BS
Departments of Microbiology and Immunology1 and Medicine2, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005822:Genetic Vectors; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011995:Recombination, Genetic; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology; D014764:Viral Proteins / Q000096:biosynthesis*; D014779:Virus Replication
D000914:Antibodies, Viral; D014764:Viral Proteins; D015847:Interleukin-4; D007371:Interferon-gamma