Potent CD8+ T-cell immunogenicity in humans of a novel heterosubtypic influenza A vaccine, MVA-NP+M1.
Potent CD8+ T-cell immunogenicity in humans of a novel heterosubtypic influenza A vaccine, MVA-NP+M1.
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DOI：
10.1093/cid/ciq015
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Gilbert SC
中科院分区：
文献类型：
--
作者：
Berthoud TK;Hamill M;Lillie PJ;Hwenda L;Collins KA;Ewer KJ;Milicic A;Poyntz HC;Lambe T;Fletcher HA;Hill AV;Gilbert SC
背景：甲型流感病毒引起偶发性大流行和频繁的流行。 对高度多态性病毒表面抗原血凝素诱导高抗体滴度的许可流感疫苗必须每年重新配制和重新接种。对高度保守的内部抗原提供保护性免疫的疫苗可以针对多种流感亚型提供更持久的保护。方法：我们制备了编码核蛋白和基质蛋白1（MVA-NP +M1）的改良安卡拉牛痘病毒（MVA）载体，并在健康成人中进行了I期临床试验。 结果：该疫苗总体上是安全的，耐受性良好，肌肉注射比皮内注射局部副作用明显减少。 在较高剂量下，全身副作用的频率和严重程度均增加，8名志愿者中有5名出现重度恶心/呕吐、不适或寒战。通过IFN-γ ELISPOT测定法测量的对NP和M1的离体T细胞应答在疫苗接种后显著增加（接种前中位数为123个斑点形成单位/百万外周血单核细胞，接种后峰值反应中位数分别为339、443和1443，低剂量皮内、低剂量肌内和高剂量肌内组），并且大多数抗原特异性T细胞是CD 8+。结论：我们的结论是，该疫苗既安全又具有显著的免疫原性，导致应答性T细胞的频率似乎比任何其他流感疫苗接种方法诱导的频率高得多。 需要进一步的研究来找到最佳剂量，并评估T细胞对保守流感蛋白的反应是否增加，从而防止流感疾病。
Background. Influenza A viruses cause occasional pandemics and frequent epidemics. Licensed influenza vaccines that induce high antibody titers to the highly polymorphic viral surface antigen hemagglutinin must be re-formulated and readministered annually. A vaccine providing protective immunity to the highly conserved internal antigens could provide longer-lasting protection against multiple influenza subtypes. Methods. We prepared a Modified Vaccinia virus Ankara (MVA) vector encoding nucleoprotein and matrix protein 1 (MVA−NP+M1) and conducted a phase I clinical trial in healthy adults. Results. The vaccine was generally safe and well tolerated, with significantly fewer local side effects after intramuscular rather than intradermal administration. Systemic side effects increased at the higher dose in both frequency and severity, with 5 out of 8 volunteers experiencing severe nausea/vomiting, malaise, or rigors. Ex vivo T-cell responses to NP and M1 measured by IFN-γ ELISPOT assay were significantly increased after vaccination (prevaccination median of 123 spot-forming units/million peripheral blood mononuclear cells, postvaccination peak response median 339, 443, and 1443 in low-dose intradermal, low-dose intramuscular, and high-dose intramuscular groups, respectively), and the majority of the antigen-specific T cells were CD8+. Conclusions. We conclude that the vaccine was both safe and remarkably immunogenic, leading to frequencies of responding T cells that appear to be much higher than those induced by any other influenza vaccination approach. Further studies will be required to find the optimum dose and to assess whether the increased T-cell response to conserved influenza proteins results in protection from influenza disease.
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作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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DOI：
10.1073/pnas.0813390106
发表时间：
2009-03-10
影响因子：
11.1
作者：
Galli, Grazia;Medini, Duccio;Castellino, Flora
通讯作者：
Castellino, Flora