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Protection against Chronic Hepatitis C Virus Infection after Rechallenge with Homologous, but Not Heterologous, Genotypes in a Chimpanzee Model

Protection against Chronic Hepatitis C Virus Infection after Rechallenge with Homologous, but Not... An open question for hepatitis C virus (HCV) vaccine development is whether the various genotypes of this virus protect against the development of chronic infection after heterologous infection with different genotypes. We approached this question by challenging chimpanzees that had recovered from HCV genotype 1a or 1b infection with 6 heterologous genotypes as well as with a homologous genotype (for chimpanzees originally infected with genotype 1a). All 9 chimpanzees rechallenged with a homologous genotype developed self-limited infections. Of 11 chimpanzees challenged with 100 chimpanzee infectious doses of heterologous genotypes, 6 developed self-limited infections, with peak viral loads in acute-phase serum that were ∼5-fold lower than those seen during primary infections. One chimpanzee (which had recovered from genotype 1b infection and was rechallenged with genotype 6a) did not develop viremia but did show an anamnestic cell-mediated immune response after rechallenge. Four of the 11 chimpanzees rechallenged with heterologous genotypes developed chronic infections with the genotypes used for rechallenge. These findings suggest that a universally protective HCV vaccine may need to incorporate epitopes from multiple genotypes http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Infectious Diseases Oxford University Press

Protection against Chronic Hepatitis C Virus Infection after Rechallenge with Homologous, but Not Heterologous, Genotypes in a Chimpanzee Model

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References (34)

Publisher
Oxford University Press
Copyright
© Published by Oxford University Press.
Subject
Major Articles and Brief Reports
ISSN
0022-1899
eISSN
1537-6613
DOI
10.1086/496889
pmid
16235167
Publisher site
See Article on Publisher Site

Abstract

An open question for hepatitis C virus (HCV) vaccine development is whether the various genotypes of this virus protect against the development of chronic infection after heterologous infection with different genotypes. We approached this question by challenging chimpanzees that had recovered from HCV genotype 1a or 1b infection with 6 heterologous genotypes as well as with a homologous genotype (for chimpanzees originally infected with genotype 1a). All 9 chimpanzees rechallenged with a homologous genotype developed self-limited infections. Of 11 chimpanzees challenged with 100 chimpanzee infectious doses of heterologous genotypes, 6 developed self-limited infections, with peak viral loads in acute-phase serum that were ∼5-fold lower than those seen during primary infections. One chimpanzee (which had recovered from genotype 1b infection and was rechallenged with genotype 6a) did not develop viremia but did show an anamnestic cell-mediated immune response after rechallenge. Four of the 11 chimpanzees rechallenged with heterologous genotypes developed chronic infections with the genotypes used for rechallenge. These findings suggest that a universally protective HCV vaccine may need to incorporate epitopes from multiple genotypes

Journal

Journal of Infectious Diseases – Oxford University Press

Published: Nov 15, 2005

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