Enhanced immunogenicity, mortality protection, and reduced viral brain invasion by alum adjuvant with an H5N1 split-virion vaccine in the ferret.
Enhanced immunogenicity, mortality protection, and reduced viral brain invasion by alum adjuvant with an H5N1 split-virion vaccine in the ferret.
复制标题
DOI：
10.1371/journal.pone.0020641
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Koster F
中科院分区：
文献类型：
--
作者：
Layton RC;Gigliotti A;Armijo P;Myers L;Knight J;Donart N;Pyles J;Vaughan S;Plourde J;Fomukong N;Harrod KS;Gao P;Koster F
与季节性流感疫苗相比，灭活的裂解病毒体禽流感疫苗的大流行前开发受到缺乏预先存在的免疫力和一些H5血凝素的免疫原性降低的挑战。需要鉴定可接受的有效佐剂以提高裂解病毒体禽流感疫苗的免疫原性。雪貂（N = 118）接种两次A/Vietnam/1203/2004裂解病毒体疫苗制剂或生理盐水，间隔21天（无佐剂：1.9 µg、7.5 µg、30 µg或生理盐水）或间隔28天（无佐剂：22.5 µg或明矾佐剂：22.5或7.5 µg）。 21或28天后，用106 EID 50的同源菌株鼻内攻毒接种疫苗的动物。通过血凝抑制和中和试验测定免疫原性。通过观察到的行为、体重减轻、体温、血细胞减少、组织病理学和病毒载量评估死亡率。用无佐剂疫苗接种后未检测到血清抗体，而明矾佐剂疫苗接种诱导了强烈的抗体应答。30 µg、7.5 µg和1.9 µg（间隔21天）无佐剂给药方案后的生存率分别为64%、43%和43%，但存活者出现体重减轻、发热和血小板减少。22.5 µg无佐剂给药方案（28天间隔）后的生存率为0%，表明该模型中的间隔存在重要差异。与无佐剂的存活者相比，任一剂量的明矾佐剂疫苗均导致93%的存活率，发病率最低，且无发热或体重减轻。与无佐剂疫苗幸存者中的高水平相比，明矾佐剂幸存者中的脑炎症的罕见性表明，与明矾佐剂相关的保护作用的改善是由于雪貂脑的早期病毒入侵显著减少。明矾佐剂显著提高了H5 N1裂解病毒粒子疫苗在雪貂模型中的效力，如通过免疫原性、死亡率、发病率和脑侵袭所测量的。
Pre-pandemic development of an inactivated, split-virion avian influenza vaccine is challenged by the lack of pre-existing immunity and the reduced immunogenicity of some H5 hemagglutinins compared to that of seasonal influenza vaccines. Identification of an acceptable effective adjuvant is needed to improve immunogenicity of a split-virion avian influenza vaccine. Ferrets (N = 118) were vaccinated twice with a split-virion vaccine preparation of A/Vietnam/1203/2004 or saline either 21 days apart (unadjuvanted: 1.9 µg, 7.5 µg, 30 µg, or saline), or 28 days apart (unadjuvanted: 22.5 µg, or alum-adjuvanted: 22.5 or 7.5 µg). Vaccinated animals were challenged intranasally 21 or 28 days later with 106 EID50 of the homologous strain. Immunogenicity was measured by hemagglutination inhibition and neutralization assays. Morbidity was assessed by observed behavior, weight loss, temperature, cytopenias, histopathology, and viral load. No serum antibodies were detected after vaccination with unadjuvanted vaccine, whereas alum-adjuvanted vaccination induced a robust antibody response. Survival after unadjuvanted dose regimens of 30 µg, 7.5 µg and 1.9 µg (21-day intervals) was 64%, 43%, and 43%, respectively, yet survivors experienced weight loss, fever and thrombocytopenia. Survival after unadjuvanted dose regimen of 22.5 µg (28-day intervals) was 0%, suggesting important differences in intervals in this model. In contrast to unadjuvanted survivors, either dose of alum-adjuvanted vaccine resulted in 93% survival with minimal morbidity and without fever or weight loss. The rarity of brain inflammation in alum-adjuvanted survivors, compared to high levels in unadjuvanted vaccine survivors, suggested that improved protection associated with the alum adjuvant was due to markedly reduced early viral invasion of the ferret brain. Alum adjuvant significantly improves efficacy of an H5N1 split-virion vaccine in the ferret model as measured by immunogenicity, mortality, morbidity, and brain invasion.
登录
查看更多内容
影响因子：
6.4
作者：
Keitel, Wendy A.;Campbell, James D.;Hill, Heather
通讯作者：
Hill, Heather
影响因子：
11.8
作者：
Lebarbenchon C;Feare CJ;Renaud F;Thomas F;Gauthier-Clerc M
通讯作者：
Gauthier-Clerc M
DOI：
10.1073/pnas.0506416102
发表时间：
2005-09-06
影响因子：
11.1
作者：
Hoffmann, E;Lipatov, AS;Webster, RG
通讯作者：
Webster, RG
影响因子：
5.4
作者：
Fang, Yuan;Rowe, Thomas;Kelvin, David J.
通讯作者：
Kelvin, David J.
影响因子：
15.8
作者：
Gillim-Ross L;Subbarao K
通讯作者：
Subbarao K