Villefroy Pascale, Letourneur Franck, Coutsinos Zoe, Mortara Lorenzo, Beyer Christian, Gras-Masse Helene, Guillet Jean-Gerard, Bourgault-Villada Isabelle
Institut Cochin, Département d'Immunologie, Hôpital Cochin, 27, rue du Faubourg Saint-Jacques, Paris, F-75014, France.
Virol J. 2006 Aug 31;3:65. doi: 10.1186/1743-422X-3-65.
Emergence of viral variants that escape CTL control is a major hurdle in HIV vaccination unless such variants affect gene regions that are essential for virus replication. Vaccine-induced multispecific CTL could also be able to control viral variants replication. To explore these possibilities, we extensively characterized CTL responses following vaccination with an epitope-based lipopeptide vaccine and challenge with pathogenic SIVmac251. The viral sequences corresponding to the epitopes present in the vaccine as well as the viral loads were then determined in every macaque following SIV inoculation.
In most cases, the emergence of several viral variants or mutants within vaccine CTL epitopes after SIV challenge resulted in increased viral loads except for a single macaque, which showed a single escape viral variant within its 6 vaccine-induced CTL epitopes.
These findings provide a better understanding of the evolution of CD8+ epitope variations after vaccination-induced CTL expansion and might provide new insight for the development of an effective HIV vaccine.
除非病毒变异体影响病毒复制所必需的基因区域，否则逃避细胞毒性T淋巴细胞（CTL）控制的病毒变异体的出现是HIV疫苗接种的主要障碍。疫苗诱导的多特异性CTL也可能能够控制病毒变异体的复制。为了探索这些可能性，我们广泛地表征了接种基于表位的脂肽疫苗后以及用致病性SIVmac251攻击后的CTL反应。然后在每只猕猴接种SIV后测定与疫苗中存在的表位相对应的病毒序列以及病毒载量。
在大多数情况下，SIV攻击后疫苗CTL表位内出现几种病毒变异体或突变体导致病毒载量增加，但有一只猕猴除外，该猕猴在其6个疫苗诱导的CTL表位内仅出现了一个逃逸病毒变异体。
这些发现有助于更好地理解接种疫苗诱导的CTL扩增后CD8 +表位变异的演变，并可能为开发有效的HIV疫苗提供新的见解。
