Vaccine-induced early control of hepatitis C virus infection in chimpanzees fails to impact on hepatic PD-1 and chronicity.
Broad T cell and B cell responses to multiple HCV antigens are observed early in individuals who control or clear HCV infection. The prevailing hypothesis has been that similar immune responses induced by prophylactic immunization would reduce acute virus replication and protect exposed individuals from chronic infection. Here, we demonstrate that immunization of naïve chimpanzees with a multicomponent HCV vaccine induced robust HCV-specific immune responses, and that all vaccinees exposed to heterologous chimpanzee-adapted HCV 1b J4 significantly reduced viral RNA in serum by 84%, and in liver by 99% as compared to controls (P=0.024 and 0.028, respectively). However, despite control of HCV in plasma and liver in the acute period, in the chronic phase, 3 of 4 vaccinated animals developed persistent infection. Analysis of expression levels of proinflammatory cytokines in serial hepatic biopsies failed to reveal an association with vaccine outcome. However, expression of IDO, CTLA-4 [corrected] and PD-1 levels in liver correlated with clearance or chronicity.


CONCLUSIONS
Despite early control of virus load, a virus-associated tolerogenic-like state can develop in certain individuals independent of vaccination history.
Rollier
Christine S
CS
Department of Virology, Biomedical Primate Research Center, GH Rijswijk, The Netherlands.
Paranhos-Baccala
Glaucia
G
Verschoor
Ernst J
EJ
Verstrepen
Babs E
BE
Drexhage
Joost A R
JA
Fagrouch
Zahra
Z
Berland
Jean-Luc
JL
Komurian-Pradel
Florence
F
Duverger
Blandine
B
Himoudi
Nourredine
N
Staib
Caroline
C
Meyr
Marcus
M
Whelan
Mike
M
Whelan
Joseph A
JA
Adams
Victoria C
VC
Adams
Victoria A
VA
Larrea
Esther
E
Riezu
José I
JI
Lasarte
Juan J
JJ
Lasarte
Juan José
JJ
Bartosch
Birke
B
Cosset
Francois-L
FL
Spaan
Willy J M
WJ
Diepolder
Helmut M
HM
Pape
Gerd R
GR
Sutter
Gerd
G
Inchauspe
Genevieve
G
Heeney
Jonathan L
JL
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000956:Antigens, Viral / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002908:Chronic Disease / Q000517:prevention & control; D016207:Cytokines / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology* / Q000517:prevention & control; D002679:Pan troglodytes; D061026:Programmed Cell Death 1 Receptor; D014761:Viral Hepatitis Vaccines / Q000627:therapeutic use*; D019562:Viral Load
D015703:Antigens, CD; D000956:Antigens, Viral; D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; D004279:DNA, Viral; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D014761:Viral Hepatitis Vaccines