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甲型（H1N1）pdm09 减毒活流感疫苗候选株在原代人鼻上皮细胞中的稳定性和复制效率评估

Evaluation of A(H1N1)pdm09 LAIV vaccine candidates stability and replication efficiency in primary human nasal epithelial cells.

作者信息

Shcherbik Svetlana, Pearce Nicholas, Carney Paul, Bazhenova Ekaterina, Larionova Natalie, Kiseleva Irina, Rudenko Larisa, Kumar Amrita, Goldsmith Cynthia S, Dugan Vivien, Stevens James, Wentworth David E, Bousse Tatiana

机构信息

Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, United States.

Battelle, Atlanta, GA 30329, United States.

出版信息

Vaccine X. 2019 Jun 19;2:100031. doi: 10.1016/j.jvacx.2019.100031. eCollection 2019 Aug 9.

DOI:10.1016/j.jvacx.2019.100031
PMID:31384746
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6668239/
Abstract

The recent reduction of live attenuated influenza vaccine (LAIV) effectiveness in multivalent formulations was particularly associated with the A(H1N1)pdm09 component. In the 2017 the WHO vaccine composition committee changed its recommendations for the A(H1N1)pdm09 component to include an A/Michigan/45/2015-like virus. We evaluated effectiveness and quality of newly developed and previous A(H1N1)pdm09 LAIV reassortants through assessment of their thermal and pH stability, receptor binding specificity and replication fitness in primary human airway epithelial cells of nasal origin (hAECN). Our analysis showed that LAIV expressed hemagglutinin (HA) and neuraminidase (NA) from an A/Michigan/45/2015-like strain A/New York/61/2015 (A/New York/61/2015-CDC-LV16A, NY-LV16A), exhibit higher thermal and pH stability compared to the previous vaccine candidates expressing HA and NA from A/California/07/2009 and A/Bolivia/559/2013 (A17/Cal09 and A17/Bol13). Reassortants A/South Africa/3626/2013-CDC-LV14A (SA-LV14A) and NY-LV16A showed preferential binding to α2,6 sialic acid (SA) receptors and replicated at higher titers and more extensively in hAECN compared to A17/Cal09 and A17/Bol13, which had an α2,3 SA receptor binding preference. Our data analysis supports selection of A/New York/61/2015-CDC-LV16A for LAIV formulation and the introduction of new assays for LAIV characterization.

摘要

近期多价配方的减毒活流感疫苗（LAIV）效力下降尤其与A（H1N1）pdm09组分有关。2017年，世界卫生组织疫苗成分委员会更改了对A（H1N1）pdm09组分的建议，纳入了一株类似A/密歇根/45/2015的病毒。我们通过评估新研发的和之前的A（H1N1）pdm09 LAIV重配株在鼻源原代人呼吸道上皮细胞（hAECN）中的热稳定性和pH稳定性、受体结合特异性及复制适应性，来评价它们的效力和质量。我们的分析表明，表达来自类似A/密歇根/45/2015毒株A/纽约/61/2015（A/纽约/61/2015-CDC-LV16A，NY-LV16A）的血凝素（HA）和神经氨酸酶（NA）的LAIV，与之前表达来自A/加利福尼亚/07/2009和A/玻利维亚/559/2013（A17/Cal09和A17/Bol13）的HA和NA的疫苗候选株相比，表现出更高的热稳定性和pH稳定性。与具有α2,3 SA受体结合偏好的A17/Cal09和A17/Bol13相比，重配株A/南非/3626/2013-CDC-LV14A（SA-LV14A）和NY-LV16A显示出对α2,6唾液酸（SA）受体的优先结合，并在hAECN中以更高滴度和更广泛地进行复制。我们的数据分析支持选择A/纽约/61/2015-CDC-LV16A用于LAIV配方，并引入新的检测方法来鉴定LAIV。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5988/6668239/9274b6a8a3d0/gr8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5988/6668239/8c196d02d644/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5988/6668239/c062a125ce69/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5988/6668239/841d6eaf806d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5988/6668239/b9ae7386b267/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5988/6668239/6fe5a87df36d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5988/6668239/e45381b69d54/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5988/6668239/9274b6a8a3d0/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5988/6668239/dba5c38f3be6/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5988/6668239/8c196d02d644/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5988/6668239/c062a125ce69/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5988/6668239/841d6eaf806d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5988/6668239/b9ae7386b267/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5988/6668239/6fe5a87df36d/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5988/6668239/e45381b69d54/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5988/6668239/9274b6a8a3d0/gr8.jpg

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