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Rapid and sustained CD4⁺ T-cell-independent immunity from adenovirus-encoded vaccine antigens

Institute of Medical Microbiology and Immunology, University of Copenhagen, The Panum Institute Building 22.5, Blegdamsvej 3C, DK-2200 Copenhagen N, Denmark

Correspondence
Peter J. Holst
p.holst{at}immi.ku.dk

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 ₂-microglobulin. We demonstrate that the ₂-microglobulin-linked epitope induced an accelerated and augmented CD8⁺ T-cell response. Furthermore, the immunity conferred by vaccination with 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 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.

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