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 Blattman, Rustom Antia

Research output: Contribution to journalArticle

22 Citations (Scopus)

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
Externally publishedYes

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Immunity
Vaccination
T-lymphocytes
immunity
vaccination
death
T-Lymphocytes
Infection
viruses
infection
Virus Diseases
Vaccines
vaccines
immunopathology
Viruses
Theoretical Models
mathematical models
adverse effects
Pathology
mutants

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Johnson, P. L. F., Kochin, B. F., McAfee, M. S., Stromnes, I. M., Regoes, R. R., Ahmed, R., ... Antia, R. (2011). Vaccination alters the balance between protective immunity, exhaustion, escape, and death in chronic infections. Journal of Virology, 85(11), 5565-5570. https://doi.org/10.1128/JVI.00166-11

Vaccination alters the balance between protective immunity, exhaustion, escape, and death in chronic infections. / Johnson, Philip L F; Kochin, Beth F.; McAfee, Megan S.; Stromnes, Ingunn M.; Regoes, Roland R.; Ahmed, Rafi; Blattman, Joseph; Antia, Rustom.

In: Journal of Virology, Vol. 85, No. 11, 06.2011, p. 5565-5570.

Research output: Contribution to journalArticle

Johnson, PLF, Kochin, BF, McAfee, MS, Stromnes, IM, Regoes, RR, Ahmed, R, Blattman, J & Antia, R 2011, 'Vaccination alters the balance between protective immunity, exhaustion, escape, and death in chronic infections', Journal of Virology, vol. 85, no. 11, pp. 5565-5570. https://doi.org/10.1128/JVI.00166-11
Johnson, Philip L F ; Kochin, Beth F. ; McAfee, Megan S. ; Stromnes, Ingunn M. ; Regoes, Roland R. ; Ahmed, Rafi ; Blattman, Joseph ; Antia, Rustom. / Vaccination alters the balance between protective immunity, exhaustion, escape, and death in chronic infections. In: Journal of Virology. 2011 ; Vol. 85, No. 11. pp. 5565-5570.
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