Cellular immune responses of older adults to four influenza vaccines: Results of a randomized, controlled comparison
Cellular immune responses of older adults to four influenza vaccines: Results of a randomized, controlled comparison
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DOI：
10.1080/21645515.2017.1337615
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发表时间：
2017-01-01
影响因子：
4.8
通讯作者：
Scheifele, David W.
中科院分区：
文献类型：
--
作者：
Kumar, Arun;McElhaney, Janet E.;Scheifele, David W.
细胞免疫对于预防老年人流感的严重并发症非常重要。由于尚不清楚新型流感疫苗是否比标准疫苗能引起更大的细胞反应，因此我们在一项针对老年人的随机试验中比较了 2 种标准疫苗和 2 种新许可的三价灭活疫苗 (TIV) 的反应。 ≥ 65 岁的非体弱成人被随机分配接受标准亚单位、MF59 佐剂亚单位、标准裂解病毒或皮内裂解病毒 TIV。用活 A/H3N2 病毒刺激接种前和接种后 3 周收获的外周血单核细胞 (PBMC)。测试 PBMC 上清液中的白细胞介素 10 (IL-10) 和干扰素 γ (IFN-gamma)，以及裂解物中的颗粒酶 B (GrB)。流式细胞术鉴定了表达细胞内IL-2、IL-10、IFN-γ、GrB 或穿孔素的CD4(+) 和CD8(+) T 细胞。评估了配对受试者样本和疫苗之间免疫接种后的差异。共有 120 名老年人参与，每组 29-31 人，人口统计匹配。病毒刺激的 PBMC 在疫苗接种前后富含 GrB，但增幅极小。免疫不会增加 IFN-γ 或 IL-10 的分泌。然而，所有组中的溶细胞效应 T 细胞 (CD8(+)GrB(+) 穿孔素(+)) 百分比在疫苗接种后显着增加，各组的平均值相似。每次接种疫苗后，CD4(+)GrB(+)穿孔素(+) T 细胞也显着增加，各疫苗之间的平均值相似。疫苗接种不会增加表达 IFN-γ、IL-2 或 IL-10 的 CD4(+) 或 CD8(+) T 细胞的低基线百分比。总之，参与者预先存在针对 H3N2 病毒的细胞免疫。所有 4 种疫苗都在相似但有限的程度上增强了细胞反应，特别是与流感临床保护相关的细胞溶解效应 CD8(+) T 细胞。
Cellular immunity is important for protection against the serious complications of influenza in older adults. As it is unclear if newer influenza vaccines elicit greater cellular responses than standard vaccines, we compared responses to 2 standard and 2 newer licensed trivalent inactivated vaccines (TIVs) in a randomized trial in older adults. Non-frail adults >= 65 y old were randomly assigned to receive standard subunit, MF59-adjuvanted subunit, standard split-virus or intradermal split-virus TIV. Peripheral blood mononuclear cells (PBMC) harvested pre- and 3-weeks post-vaccination were stimulated with live A/H3N2 virus. PBMC supernatants were tested for interleukin 10 (IL-10) and interferon gamma (IFN-gamma), and lysates for granzyme B (GrB). Flow cytometry identified CD4(+) and CD8(+) T-cells expressing intracellular IL-2, IL-10, IFN-gamma, GrB, or perforin. Differences following immunization were assessed for paired subject samples and among vaccines. 120 seniors participated, 29-31 per group, which were well matched demographically. Virus-stimulated PBMCs were GrB-rich before and after vaccination, with minimal increases evident. Immunization did not increase secretion of IFN-gamma or IL-10. However, cytolytic effector T-cells (CD8(+)GrB(+)perforin(+)) increased significantly in percentage post-vaccination in all groups, to similar mean values across groups. CD4(+)GrB(+)perforin(+) T-cells also increased significantly after each vaccine, to similar mean values among vaccines. Vaccination did not increase the low baseline percentages of CD4(+) or CD8(+) T-cells expressing IFN-gamma, IL-2 or IL-10 . In conclusion, participants had pre-existing cellular immunity to H3N2 virus. All 4 vaccines boosted cellular responses to a similar but limited extent, particularly cytolytic effector CD8(+) T-cells associated with clinical protection against influenza.