Role of avidity and breadth of the CD4 T cell response in progression to AIDS.
The great variability in the time between infection with HIV and the onset of AIDS has been the object of intense study. In the current work, we examine a mathematical model that focuses on the role of immune response variability between patients. We study the effect of variation in both the avidity and the breadth of the immune response on within-patient disease dynamics, viral setpoint and time to AIDS. We conclude that immune response variability can explain the observed variability in disease progression to a large extent. It turns out that the avidity, more than the breadth of the immune response, determines disease progression, and that the average avidity of the five best clones is a much better correlate for disease progression than the total number of clones responding. For the design of vaccines, this would suggest that, if given the choice between stimulating a broader, but average avidity response or a narrower high-avidity response, the latter option would yield better control of virus load and consequently slow down disease progression.
Korthals Altes
Hester
H
Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, PO Box 94084, 1090 GB Amsterdam, The Netherlands. hester.korthals.altes@rivm.nl
de Boer
Rob
R
Boerlijst
Maarten
M
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D000915:Antibody Affinity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003198:Computer Simulation; D018450:Disease Progression; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D018448:Models, Immunological