Cross-reactivity of hepatitis C virus specific vaccine-induced T cells at immunodominant epitopes

被引:32
|
作者
Kelly, Christabel [1 ]
Swadling, Leo [1 ]
Brown, Anthony [1 ]
Capone, Stefania [2 ]
Folgori, Antonella [2 ]
Salio, Mariolina [3 ]
Klenerman, Paul [1 ,4 ,5 ]
Barnes, Eleanor [1 ,4 ,5 ]
机构
[1] Univ Oxford, Nuffield Dept Med, Oxford, England
[2] Okairos, Rome, Italy
[3] WIMM, MRC Human Immunol Unit, Oxford, England
[4] Oxford NIHR BRC, Oxford, England
[5] Translat Gastroenterol Unit, Oxford, England
基金
英国医学研究理事会; 英国惠康基金;
关键词
Adenovirus; Epitopes; Hepatitis C virus; T cells; Vaccination; Variability; IMMUNE-RESPONSES; INFECTION; EVASION;
D O I
10.1002/eji.201444686
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Viral diversity is a challenge to the development of a hepatitis C virus (HCV) vaccine. Following vaccination of humans with adenoviral vectors, we determined the capacity of T cells to target common viral variants at immundominant epitopes ex vivo. We identified two major variants for epitopes NS3(1073) and NS3(1446), and multiple variants for epitope NS3(1406) that occurred in >5% of genotype 1 and 3 sequences at a population level. Cross-reactivity of vaccine-induced T cells was determined using variant peptides in IFN- ELISPOT assays. Vaccine-induced T cells targeted approximately 90% of NS3(1073) genotype 1 sequences and 50% of NS3(1446) genotype 1 and 3 sequences. For NS3(1406,) 62% of subtype-1b sequences were targeted. Next, we assessed whether an in vitro priming system, using dendritic cells and T cells from healthy donors, could identify a variant of NS3(1406) that was maximally cross-reactive. In vitro priming assays showed that of those tested the NS3(1406) vaccine variant was the most immunogenic. T cells primed with genotype 1 variants from subtype 1a or 1b were broadly cross-reactive with other variants from the same subtype. We conclude that immunization with candidate HCV adenoviral vaccines generates cross-reactive T cells at immunodominant epitopes. The degree of cross-reactivity varies between epitopes and may be HCV-subtype specific.
引用
收藏
页码:309 / 316
页数:8
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