Immunization with chaperone-peptide complex induces low-avidity cytotoxic T lymphocytes providing transient protection against herpes simplex virus infection.
Heat shock proteins loaded with viral peptides were shown to induce a CD8+ T cell response and confer protective immunity against challenge with herpes simplex virus (HSV). The delivery system consisted of recombinant human hsp70 coupled to the peptide SSIEFARL, which is the immunodominant peptide epitope, recognized by HSV specific T cells in C57BL/6 mice. Immunization resulted in CD8+ T-cell responses, measured by peptide-specific tetramers and peptide-induced intracellular gamma interferon expression and cytotoxicity, similar to responses resulting from immunization with a recombinant vaccinia virus that expressed SSIEFARL as a minigene (VvgB) and UV-inactivated HSV. However, the durability of the hsp70-SSIEFARL response was less than that resulting from VvgB and HSV immunization and in addition the CD8+ T-cell responses in the memory phase were functionally less effective. Mice challenged soon after immunization showed excellent immunity, but by 90 days postimmunization this had waned to be significantly less than the level of immunity in both VvgB- and HSV-immunized mice.
Kumaraguru
Udayasankar
U
Department of Microbiology and Department of Biochemistry, Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee 37996-0845, USA.
Gierynska
Malgorzata
M
Norman
Shanna
S
Bruce
Barry D
BD
Rouse
Barry T
BT
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002452:Cell Count; D018833:Chaperonins / Q000008:administration & dosage* / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D005822:Genetic Vectors; D018840:HSP70 Heat-Shock Proteins / Q000008:administration & dosage / Q000096:biosynthesis; D006561:Herpes Simplex / Q000517:prevention & control*; D016882:ISCOMs / Q000008:administration & dosage*; D007114:Immunization; D016056:Immunodominant Epitopes / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D007371:Interferon-gamma / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000096:biosynthesis; D018139:Simplexvirus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D015164:Vaccines, Inactivated; D014616:Vaccinia virus / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology*
D018840:HSP70 Heat-Shock Proteins; D016882:ISCOMs; D016056:Immunodominant Epitopes; D011994:Recombinant Proteins; D015164:Vaccines, Inactivated; D014764:Viral Proteins; D007371:Interferon-gamma; D018833:Chaperonins