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 heterologous, genotypes in a chimpanzee model
复制标题
DOI：
10.1086/496889
复制
发表时间：
2005-11-15
影响因子：
6.4
通讯作者：
Shata, MT
中科院分区：
文献类型：
--
作者：
Prince, AM;Brotman, B;Shata, MT
丙型肝炎病毒（HCV）疫苗开发的一个悬而未决的问题是，该病毒的各种基因型是否可以防止不同基因型异源感染后发生慢性感染。我们通过用 6 种异源基因型以及同源基因型（对于最初感染基因型 1a 的黑猩猩）来挑战从 HCV 基因型 1a 或 1b 感染中恢复的黑猩猩来解决这个问题。所有 9 只黑猩猩再次受到同源基因型攻击后都出现了自限性感染。在 11 只黑猩猩中，接受 100 种黑猩猩感染剂量的异源基因型攻击，其中 6 只出现自限性感染，急性期血清中的病毒载量峰值比初次感染时低 5 倍。一只黑猩猩（已从基因型 1b 感染中恢复并再次接受基因型 6a 攻击）并未出现病毒血症，但在再次攻击后确实表现出记忆细胞介导的免疫反应。在 11 只黑猩猩中，有 4 只再次受到异源基因型的攻击，其中 4 只因再次攻击所用的基因型而出现慢性感染。这些发现表明，普遍保护性的 HCV 疫苗可能需要纳入多种基因型的表位。
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 similar to 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.