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确定甲型H1N1流感减毒活疫苗效力降低的根本原因：低病毒适应性导致毒株间竞争。

Defining the root cause of reduced H1N1 live attenuated influenza vaccine effectiveness: low viral fitness leads to inter-strain competition.

作者信息

Dibben Oliver, Crowe Jonathan, Cooper Shaun, Hill Laura, Schewe Katarzyna E, Bright Helen

机构信息

Flu-BPD, Biopharmaceutical Development, R&D, AstraZeneca, Liverpool, UK.

出版信息

NPJ Vaccines. 2021 Mar 12;6(1):35. doi: 10.1038/s41541-021-00300-z.

DOI:10.1038/s41541-021-00300-z
PMID:33712628
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7955111/
Abstract

In the 2013-14 and 2015-16 influenza seasons, reduced vaccine effectiveness (VE) was observed for the H1N1 component of the FluMist quadrivalent live attenuated influenza vaccine (QLAIV) in the USA, leading to loss of Advisory Committee on Immunization Practices recommendation. Here we demonstrate in ferrets that 2015-16A/H1N1pdm09 vaccine strain A/Bolivia/559/2013 (A/BOL13) is outcompeted in trivalent (TLAIV) and QLAIV formulations, leading to reduced protection from wild-type challenge. While monovalent (MLAIV) A/BOL13 provided significant protection from wild-type virus shedding and fever at doses as low as 3.0 log fluorescent focus units (FFU), it failed to provide a similar level of protection in TLAIV or QLAIV formulation, even at a 6.0 log FFU dose. Conversely, clinically effective H1N1 strain A/New Caledonia/20/1999 provided significant protection in MLAIV, TLAIV, and QLAIV formulations. In conclusion, reduced A/BOL13 replicative fitness rendered it susceptible to inter-strain competition in QLAIV, contributing to its reduced VE in the 2015-16 season.

摘要

在2013 - 14年和2015 - 16年流感季节，美国观察到四价流感减毒活疫苗（QLAIV）FluMist的H1N1组分疫苗效力（VE）降低，导致免疫实践咨询委员会撤销了相关推荐。在此我们在雪貂中证明，2015 - 16年A/H1N1pdm09疫苗株A/玻利维亚/559/2013（A/BOL13）在三价（TLAIV）和QLAIV制剂中竞争力不足，导致对野生型攻击的保护作用降低。虽然单价（MLAIV）A/BOL13在低至3.0 log荧光灶单位（FFU）剂量时能显著保护免受野生型病毒脱落和发热影响，但在TLAIV或QLAIV制剂中，即使在6.0 log FFU剂量下也未能提供类似水平的保护。相反，临床有效的H1N1株A/新喀里多尼亚/20/1999在MLAIV、TLAIV和QLAIV制剂中均提供了显著保护。总之，A/BOL13复制适应性降低使其在QLAIV中易受株间竞争影响，导致其在2015 - 16年季节的疫苗效力降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb1/7955111/a7151f7f180d/41541_2021_300_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb1/7955111/69d8fa25af6b/41541_2021_300_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb1/7955111/eed68985499d/41541_2021_300_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb1/7955111/5ebac6b65989/41541_2021_300_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb1/7955111/c051216574e2/41541_2021_300_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb1/7955111/9d3fe83f4b47/41541_2021_300_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb1/7955111/a7151f7f180d/41541_2021_300_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb1/7955111/69d8fa25af6b/41541_2021_300_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb1/7955111/eed68985499d/41541_2021_300_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb1/7955111/5ebac6b65989/41541_2021_300_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb1/7955111/c051216574e2/41541_2021_300_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb1/7955111/9d3fe83f4b47/41541_2021_300_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb1/7955111/a7151f7f180d/41541_2021_300_Fig6_HTML.jpg

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