AS03-adjuvanted H5N1 vaccine promotes antibody diversity and affinity maturation, NAI titers, cross-clade H5N1 neutralization, but not H1N1 cross-subtype neutralization.
AS03-adjuvanted H5N1 vaccine promotes antibody diversity and affinity maturation, NAI titers, cross-clade H5N1 neutralization, but not H1N1 cross-subtype neutralization.
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DOI：
10.1038/s41541-018-0076-2
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发表时间：
2018
期刊：
影响因子：
9.2
通讯作者：
and the CHI Consortium
中科院分区：
文献类型：
--
作者：
Khurana S;Coyle EM;Manischewitz J;King LR;Gao J;Germain RN;Schwartzberg PL;Tsang JS;Golding H;and the CHI Consortium
对禽流感灭活疫苗的免疫反应较差，部分原因是缺乏免疫记忆。佐剂显着增加病毒中和滴度。我们对 FDA 批准的 H5N1-A/印度尼西亚佐剂疫苗（在存在或不存在 AS03 的情况下施用）后的多克隆抗体反应进行了全面分析。使用全基因组片段噬菌体展示文库，我们观察到与未佐剂的疫苗相比，AS03 诱导病毒血凝素 (HA) 和神经氨酸酶的抗体表位多样性。此外，AS03 促进了对正确折叠的 H5-HA1（但不包括 HA2）结构域的显着抗体亲和力成熟，这与针对疫苗和异源 H5N1 毒株的中和滴度相关。然而，没有观察到 Group1-H1N1 季节性毒株的异亚型交叉中和作用增加。 AS03-H5N1疫苗还诱导了更高的神经氨酸酶抑制抗体滴度。这项研究深入了解了 AS03 佐剂对 H5N1 疫苗诱导的抗体反应的不同影响，这可能有助于优化未来疫苗的疫苗平台，从而改善对季节性和大流行性流感病毒株的保护。佐剂 AS03 提高了禽流感疫苗识别和结合病毒颗粒目标的能力。禽流感病毒被认为是一种大流行威胁，由灭活病毒制成的疫苗的功效有限。然而，AS03 等佐剂能够增强宿主的免疫力，这促使美国食品和药物管理局的 Surender Khurana 和同事研究如何增强宿主的免疫力。在 H5N1 疫苗试验中，研究人员发现 AS03 通过增加抗体与病毒表面蛋白结合的程度、多样性和强度来改善免疫反应，这可能导致所观察到的测试病毒的中和作用以及对其他 H5N1 毒株的功效增加。 AS03 佐剂疫苗不能中和季节性 H1N1 流感病毒株。这项研究可能会部分阐明 AS03 的作用，从而为未来的疫苗开发工作提供信息。
Immune responses to inactivated vaccines against avian influenza are poor due in part to lack of immune memory. Adjuvants significantly increased virus neutralizing titers. We performed comprehensive analyses of polyclonal antibody responses following FDA-approved adjuvanted H5N1-A/Indonesia vaccine, administered in presence or absence of AS03. Using Whole Genome Fragment Phage Display Libraries, we observed that AS03 induced antibody epitope diversity to viral hemagglutinin (HA) and neuraminidase compared with unadjuvanted vaccine. Furthermore, AS03 promoted significant antibody affinity maturation to properly folded H5-HA1 (but not to HA2) domain, which correlated with neutralization titers against both vaccine and heterologous H5N1 strains. However, no increase in heterosubtypic cross-neutralization of Group1-H1N1 seasonal strains was observed. AS03-H5N1 vaccine also induced higher neuraminidase inhibition antibody titers. This study provides insight into the differential impacts of AS03 adjuvant on H5N1 vaccine-induced antibody responses that may help optimize vaccine platforms for future vaccines with improved protection against seasonal and pandemic influenza strains. Adjuvant AS03 improves a bird flu vaccine’s ability to recognize and bind to virion targets. Avian influenza viruses are considered a pandemic threat, and vaccines made from inactivated virus are limited in their efficacy. However, adjuvants such as AS03 have the ability to augment a host’s immunity, prompting Surender Khurana and colleagues from the United States’ Food and Drug Administration to investigate how. In an H5N1 vaccine trial, researchers found that AS03 improved immune responses by increasing the degree, diversity, and intensity of antibody binding to viral surface proteins, which likely caused the observed increase in the neutralization of the virus tested as well as efficacy against other H5N1 strains. The AS03-adjuvanted vaccine did not neutralize seasonal H1N1 influenza strains. This study may inform future vaccine development efforts by partially illuminating the effects of AS03.
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影响因子：
17.1
作者：
Andrews SF;Huang Y;Kaur K;Popova LI;Ho IY;Pauli NT;Henry Dunand CJ;Taylor WM;Lim S;Huang M;Qu X;Lee JH;Salgado-Ferrer M;Krammer F;Palese P;Wrammert J;Ahmed R;Wilson PC
通讯作者：
Wilson PC
影响因子：
15.8
作者：
Khurana S;Suguitan AL Jr;Rivera Y;Simmons CP;Lanzavecchia A;Sallusto F;Manischewitz J;King LR;Subbarao K;Golding H
通讯作者：
Golding H
影响因子：
120.7
作者：
Jackson, Lisa A.;Campbell, James D.;Bellamy, Abbie R.
通讯作者：
Bellamy, Abbie R.
影响因子：
5.4
作者：
Carter, Donald M.;Darby, Christopher A.;Ross, Ted M.
通讯作者：
Ross, Ted M.
DOI：
10.1073/pnas.0903181106
发表时间：
2009-05-12
影响因子：
11.1
作者：
Galli, Grazia;Hancock, Kathy;Stephenson, Iain
通讯作者：
Stephenson, Iain