Evaluations for in vitro correlates of immunogenicity of inactivated influenza a H5, H7 and H9 vaccines in humans.
Evaluations for in vitro correlates of immunogenicity of inactivated influenza a H5, H7 and H9 vaccines in humans.
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DOI：
10.1371/journal.pone.0050830
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Air GM
中科院分区：
文献类型：
--
作者：
Couch RB;Decker WK;Utama B;Atmar RL;Niño D;Feng JQ;Halpert MM;Air GM
人类对甲型H5N1、甲型H9N1和甲型H7灭活疫苗的血清抗体反应各不相同，但往往很低，特别是对于没有佐剂的亚单位疫苗，尽管血凝素(HA)浓度预计会产生良好的反应。为了帮助了解亚单位疫苗的低反应性，我们评估了甲型H5N1、H9N2、H7N7和2009年大流行(H1N1)疫苗的抗原摄取、处理和呈递给T细胞的情况，抗体结合分析和凝胶分析中疫苗HA的构象，不同红细胞的HA滴度，以及电子显微镜(EM)中疫苗的形态。在人类中评估的H5、H7、H9和H1疫苗制剂的抗原摄取、加工和呈递似乎正常。在与疫苗和匹配病毒的抗体相互作用中没有发现差异；虽然在免疫印迹中没有检测到H7三聚体，但没有发现HA抗原构象的异常。H7疫苗的最低HA效价为1：4，H9疫苗的最低HA效价为1：661；这些疫苗诱导的抗体反应最少。甲型H1N1流感疫苗对人类的免疫原性最强；完整的病毒和病毒片段在EM中占主导地位。一种好的免疫原性A(H9N2)疫苗主要含有病毒膜颗粒，外加HA和NA。免疫原性中等的A(H5N1)疫苗大多是带有星状的模糊结构单元；免疫原性最低的A(H7N7)疫苗大多含有5-20 nm的小结构。每一种甲型流感灭活疫苗的抗原摄取、加工和呈递到人类T细胞以及HA的构象都是正常的。低HA滴度与低免疫原性相关，颗粒或裂解病毒片段的存在与高免疫原性相关。
Serum antibody responses in humans to inactivated influenza A (H5N1), (H9N2) and A (H7) vaccines have been varied but frequently low, particularly for subunit vaccines without adjuvant despite hemagglutinin (HA) concentrations expected to induce good responses. To help understand the low responses to subunit vaccines, we evaluated influenza A (H5N1), (H9N2), (H7N7) vaccines and 2009 pandemic (H1N1) vaccines for antigen uptake, processing and presentation by dendritic cells to T cells, conformation of vaccine HA in antibody binding assays and gel analyses, HA titers with different red blood cells, and vaccine morphology in electron micrographs (EM). Antigen uptake, processing and presentation of H5, H7, H9 and H1 vaccine preparations evaluated in humans appeared normal. No differences were detected in antibody interactions with vaccine and matched virus; although H7 trimer was not detected in western blots, no abnormalities in the conformation of the HA antigens were identified. The lowest HA titers for the vaccines were <1∶4 for the H7 vaccine and 1∶661 for an H9 vaccine; these vaccines induced the fewest antibody responses. A (H1N1) vaccines were the most immunogenic in humans; intact virus and virus pieces were prominent in EM. A good immunogenic A (H9N2) vaccine contained primarily particles of viral membrane with external HA and NA. A (H5N1) vaccines intermediate in immunogenicity were mostly indistinct structural units with stellates; the least immunogenic A (H7N7) vaccine contained mostly small 5 to 20 nm structures. Antigen uptake, processing and presentation to human T cells and conformation of the HA appeared normal for each inactivated influenza A vaccine. Low HA titer was associated with low immunogenicity and presence of particles or split virus pieces was associated with higher immunogenicity.
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影响因子：
6.4
作者：
Keitel, Wendy A.;Campbell, James D.;Hill, Heather
通讯作者：
Hill, Heather
DOI：
10.1001/jama.1958.02990100022005
发表时间：
1958-01-01
影响因子：
120.7
作者：
HILLEMAN, MR;FLATLEY, FJ;LEVINSON, DJ
通讯作者：
LEVINSON, DJ
影响因子：
158.5
作者：
Ehrlich, Hartmut J.;Mueller, Markus;Barrett, P. Noel
通讯作者：
Barrett, P. Noel
影响因子：
5.5
作者：
Gulati, U;Kumari, K;Air, GM
通讯作者：
Air, GM
影响因子：
5.4
作者：
Hehme, N;Engelmann, H;Sänger, R
通讯作者：
Sänger, R