Abstract:
:DNA vaccination is an efficient way to induce CD8+ T cell memory, but it is still unclear to what extent such memory responses afford protection in vivo. To study this, we induced CD8+ memory responses directed towards defined viral epitopes, using DNA vaccines encoding immunodominant MHC class I-restricted epitopes of lymphocytic choriomeningitis virus covalently linked to beta2-microglobulin. This vaccine construct primed for a stronger recall response than did a more conventional minigene construct. Despite this, vaccinated mice were only protected against systemic infection whereas protection against the consequences of peripheral challenge was limited. Phenotypic analysis revealed that DNA vaccine-primed CD8+ T cells in uninfected mice differed from virus-primed CD8+ T cells particularly regarding expression of very-late antigen (VLA)-4, an adhesion molecule important for targeting T cells to inflammatory sites. Thus, our DNA vaccine induces a long-lived memory CD8+ T cell population that provides efficient protection against high-dose systemic infection. However, viral replication in solid non-lymphoid organs is not curtailed sufficiently fast to prevent significant virus-induced inflammation. Our results suggest that this is due to qualitative limitations of the primed CD8+ T cells.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Bartholdy C,Stryhn A,Hansen NJ,Buus S,Thomsen ARdoi
10.1002/eji.200323928keywords:
subject
Has Abstractpub_date
2003-07-01 00:00:00pages
1941-8issue
7eissn
0014-2980issn
1521-4141journal_volume
33pub_type
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