Rapid and sustained CD4(+) T-cell-independent immunity from adenovirus-encoded vaccine antigens.
Many novel vaccine strategies rely on recombinant viral vectors for antigen delivery, and adenovirus vectors have emerged among the most potent of these. In this report, we have compared the immune response induced through priming with adenovirus vector-encoded full-length viral protein to that elicited with an adenovirus-encoded minimal epitope covalently linked to beta(2)-microglobulin. We demonstrate that the beta(2)-microglobulin-linked epitope induced an accelerated and augmented CD8(+) T-cell response. Furthermore, the immunity conferred by vaccination with beta(2)-microglobulin-linked lymphocytic choriomeningitis virus (LCMV)-derived epitopes was long-lived and protective. Notably, in contrast to full-length protein, the response elicited with the beta(2)-microglobulin-linked LCMV-derived epitope was CD4(+) T-cell independent. Furthermore, virus-specific CD8(+) T cells primed in the absence of CD4(+) T-cell help were sustained in the long term and able to expand and control a secondary challenge with LCMV. Our results demonstrate that modifications to the antigen used in adenovirus vaccines may be used to improve the induced T-cell response. Such a strategy for CD4(+) T-cell-independent immunity from adenovirus vectors offers prospects for vaccination against opportunistic pathogens in AIDS patients and possibly immunotherapy in chronic virus infections.
Holst
Peter J
PJ
Institute of Medical Microbiology and Immunology, University of Copenhagen, The Panum Institute Building 22.5, Blegdamsvej 3C, DK-2200 Copenhagen N, Denmark.
Bartholdy
Christina
C
Institute of Medical Microbiology and Immunology, University of Copenhagen, The Panum Institute Building 22.5, Blegdamsvej 3C, DK-2200 Copenhagen N, Denmark.
Stryhn
Annette
A
Institute of Medical Microbiology and Immunology, University of Copenhagen, The Panum Institute Building 22.5, Blegdamsvej 3C, DK-2200 Copenhagen N, Denmark.
Thomsen
Allan R
AR
Institute of Medical Microbiology and Immunology, University of Copenhagen, The Panum Institute Building 22.5, Blegdamsvej 3C, DK-2200 Copenhagen N, Denmark.
Christensen
Jan P
JP
Institute of Medical Microbiology and Immunology, University of Copenhagen, The Panum Institute Building 22.5, Blegdamsvej 3C, DK-2200 Copenhagen N, Denmark.
D000256:Adenoviridae / Q000276:immunology*; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D005822:Genetic Vectors; D008099:Liver / Q000821:virology; D008168:Lung / Q000821:virology; D016131:Lymphocyte Subsets / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D013154:Spleen / Q000821:virology; D016019:Survival Analysis; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology
D000956:Antigens, Viral; D000939:Epitopes; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D001613:beta 2-Microglobulin