4-1BBL coexpression enhances HIV-specific CD8 T cell memory in a poxvirus prime-boost vaccine.
We have constructed a recombinant fowlpox virus expressing HIV antigens and the costimulatory molecule 4-1BBL. When included in the boost, but not the prime of a poxvirus prime-boost strategy, 4-1BBL significantly enhanced the anti-HIV T cell response generated to this vaccination in BALB/c mice, as detected by ex vivo IFNgamma ELISPOT responses, intracellular cytokine staining to HIV Gag antigens, and enumeration of Gag-reactive CD8 T cells. 4-1BBL however, is not capable of modulating the CD4 T cell response, nor the antibody response to this vaccination strategy. Enhancement of the T cell response by 4-1BBL continues into the memory phase, as detected 2 months post vaccination. This data is the first to show modulation of the immune response to a viral vaccine by coexpression of 4-1BBL and supports this strategy as an exciting approach for enhancement of T cell memory in prime-boost vaccines.
Harrison
Jodie M
JM
Department of Immunology and Genetics, The John Curtin School of Medical Research, Canberra City, Australia.
Bertram
Edward M
EM
Boyle
David B
DB
Coupar
Barbara E H
BE
Ranasinghe
Charani
C
Ramshaw
Ian A
IA
D053330:4-1BB Ligand / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000918:Antibody Specificity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005587:Fowlpox virus / Q000276:immunology*; D006678:HIV / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D007117:Immunization, Secondary; D007156:Immunologic Memory / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D014614:Vaccines, Synthetic / Q000276:immunology
D053330:4-1BB Ligand; D000939:Epitopes; D015488:HIV Antigens; D014614:Vaccines, Synthetic