title: Vaccination alters the balance between protective immunity, exhaustion, escape, and death in chronic infections.
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.
authors.affiliation: Department of Biology, Emory University, Atlanta, Georgia, USA. plfjohnson@emory.edu
authors.forename: Philip L F
authors.initials: PL
authors.lastname: Johnson
authors.forename: Beth F
authors.initials: BF
authors.lastname: Kochin
authors.forename: Megan S
authors.initials: MS
authors.lastname: McAfee
authors.forename: Ingunn M
authors.initials: IM
authors.lastname: Stromnes
authors.forename: Roland R
authors.initials: RR
authors.lastname: Regoes
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.forename: Joseph N
authors.initials: JN
authors.lastname: Blattman
authors.forename: Rustom
authors.initials: R
authors.lastname: Antia
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D008962:Models, Theoretical; D014611:Vaccination / Q000009:adverse effects*; D014612:Vaccines / Q000009:adverse effects* / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology* / Q000401:mortality / Q000473:pathology*
chemical_list: D014612:Vaccines