Vaccination alters the balance between protective immunity, exhaustion, escape, and death in chronic infections

Philip L F Johnson, Beth F. Kochin, Megan S. McAfee, Ingunn M. Stromnes, Roland R. Regoes, Rafi Ahmed, Joseph N. Blattman, Rustom Antia

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

While T cell-based vaccines have the potential to provide protection against chronic virus infections, they also have the potential to generate immunopathology following subsequent virus infection. We develop a mathematical model to investigate the conditions under which T cells lead to protection versus adverse pathology. The model illustrates how the balance between virus clearance and immune exhaustion may be disrupted when vaccination generates intermediate numbers of specific CD8 T cells. Surprisingly, our model suggests that this adverse effect of vaccination is largely unaffected by the generation of mutant viruses that evade T cell recognition and cannot be avoided by simply increasing the quality (affinity) or diversity of the T cell response. These findings should be taken into account when developing vaccines against persistent infections.

Original languageEnglish (US)
Pages (from-to)5565-5570
Number of pages6
JournalJournal of virology
Volume85
Issue number11
DOIs
StatePublished - Jun 2011

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