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重新审视 1976 年“猪流感”疫苗临床试验:交叉反应性血凝素和神经氨酸酶抗体及其在小鼠中预防 2009 年 H1N1 大流行病毒的作用。

Revisiting the 1976 "swine flu" vaccine clinical trials: cross-reactive hemagglutinin and neuraminidase antibodies and their role in protection against the 2009 H1N1 pandemic virus in mice.

机构信息

Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, Maryland 20892, USA.

出版信息

Clin Infect Dis. 2011 Dec;53(12):1179-87. doi: 10.1093/cid/cir693. Epub 2011 Oct 5.

DOI:10.1093/cid/cir693
PMID:21976461
Abstract

BACKGROUND

The 2009 H1N1 pandemic viruses are genetically similar to A/New Jersey/76 H1N1 virus (NJ/76), the strain selected for the 1976 "swine flu" vaccines. Approximately 45 million people in the United States were vaccinated against NJ/76 30 years ago, but the impact of this nationwide immunization on the current pandemic is largely unknown.

METHODS

Archived human serum samples collected during the 1976 swine flu vaccine trials were assessed for cross-reactive antibody responses to the 2009 H1N1 pandemic viruses.

RESULTS

Administration of an NJ/76 monovalent vaccine or the combination of a bivalent vaccine (NJ/76 H1N1 and A/Victoria/75 H3N2) plus a B/Hong Kong/72 monovalent vaccine increased hemagglutinin inhibition (HAI) and neuraminidase inhibition (NAI) antibodies cross-reacting with the 2009 H1N1 pandemic viruses. We showed that cross-reactive human HAI antibodies elicited by the 1976 swine flu vaccination played a dominant role in protecting recipient mice against the wild-type A/California/04/2009. Cross-reactive human NAI antibodies were also protective in recipient mice after a lethal challenge with a hemagglutinin mismatched virus bearing the A/California/04/2009 neuraminidase gene. Transfer of human serum samples with an original HAI titer of 43 or an original NAI titer of 472 was estimated to protect 50% of recipient mice from a lethal infection under the experimental conditions described.

CONCLUSIONS

The 1976 swine flu vaccination induced cross-reactive HAI and NAI antibodies that were functionally protective in mice, suggesting that this vaccination campaign might have had a positive impact on older adults (≥50 years) in the United States during the 2009 H1N1 pandemic.

摘要

背景

2009 年 H1N1 大流行病毒在遗传学上与 A/New Jersey/76 H1N1 病毒(NJ/76)相似,后者是 1976 年“猪流感”疫苗选用的毒株。大约 4500 万美国人在 30 年前接种了针对 NJ/76 的疫苗,但这种全国性免疫接种对当前大流行的影响在很大程度上尚不清楚。

方法

评估了在 1976 年猪流感疫苗试验中收集的存档人血清样本对 2009 年 H1N1 大流行病毒的交叉反应性抗体反应。

结果

接种 NJ/76 单价疫苗或双价疫苗(NJ/76 H1N1 和 A/Victoria/75 H3N2)加 B/Hong Kong/72 单价疫苗均可增加与 2009 年 H1N1 大流行病毒交叉反应的血凝素抑制(HAI)和神经氨酸酶抑制(NAI)抗体。我们表明,1976 年猪流感疫苗接种引起的交叉反应性人 HAI 抗体在保护受体小鼠免受野生型 A/California/04/2009 的侵害方面发挥了主导作用。在受体小鼠中用血凝素错配病毒进行致死性攻击后,具有 A/California/04/2009 神经氨酸酶基因的交叉反应性人 NAI 抗体也具有保护作用。估计转移原始 HAI 滴度为 43 或原始 NAI 滴度为 472 的人血清样本可在描述的实验条件下保护 50%的受体小鼠免受致死性感染。

结论

1976 年猪流感疫苗接种诱导了交叉反应性 HAI 和 NAI 抗体,在小鼠中具有功能保护作用,表明在 2009 年 H1N1 大流行期间,该疫苗接种运动可能对美国的老年人(≥50 岁)产生了积极影响。

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