Pre-existing Antineuraminidase Antibodies Are Associated With Shortened Duration of Influenza A(H1N1)pdm Virus Shedding and Illness in Naturally Infected Adults
Pre-existing Antineuraminidase Antibodies Are Associated With Shortened Duration of Influenza A(H1N1)pdm Virus Shedding and Illness in Naturally Infected Adults
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DOI：
10.1093/cid/ciz639
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发表时间：
2020-06-01
影响因子：
11.8
通讯作者：
Gordon, Aubree
中科院分区：
文献类型：
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作者：
Maier, Hannah E.;Nachbagauer, Raffael;Gordon, Aubree
背景流感在世界范围内造成了巨大的负担，目前的季节性流感疫苗效果不佳。为了开发更好、更广泛的保护性疫苗，需要更彻底地了解靶向流感病毒表面抗原、血凝素（HA）（包括头部和茎部区域）和神经氨酸酶（NA）的抗体如何影响流感疾病和病毒传播。我们使用了一个病例确定的，以社区为基础的家庭流感病毒传播研究集在尼加拉瓜马那瓜。使用170例逆转录-聚合酶链反应（RT-PCR）证实的甲型H1N1流感病毒pdm感染和45例血清学证实感染的家庭成员的数据，我们使用加速失效时间模型研究了预先存在的NA、血凝抑制和HA茎抗体水平与流感病毒脱落和疾病持续时间的关系。在RT-PCR证实的成人感染中，预先存在的抗NA抗体水平>= 40与69%（95%置信区间[CI]，34-85%）缩短的脱落持续时间（平均值，1.0 vs 3.2天）相关。神经氨酸酶抗体水平>= 80与进一步缩短脱落和显著缩短症状持续时间相关（流感样疾病，82%; 95%CI，39-95%）。在经RT-PCR证实的儿童感染中，血凝抑制滴度≥ 1：20与32%（95%CI，13-47%）的脱落持续时间缩短（平均3.9 vs 6.0天）相关。我们的研究结果表明，抗NA抗体在减少成人流感疾病持续时间方面发挥着重要作用，并可能影响传播，尤其是在成人中。神经氨酸酶应被视为下一代流感病毒疫苗开发的额外靶点。
Background. Influenza causes a substantial burden worldwide, and current seasonal influenza vaccine has suboptimal effectiveness. To develop better, more broadly protective vaccines, a more thorough understanding is needed of how antibodies that target the influenza virus surface antigens, hemagglutinin (HA) (including head and stalk regions) and neuraminidase (NA), impact influenza illness and virus transmission.Methods. We used a case-ascertained, community-based study of household influenza virus transmission set in Managua, Nicaragua. Using data from 170 reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed influenza virus A(H1N1) pdm infections and 45 household members with serologically confirmed infection, we examined the association of pre-existing NA, hemagglutination inhibiting, and HA stalk antibody levels and influenza viral shedding and disease duration using accelerated failure time models.Results. Among RT-PCR-confirmed infections in adults, pre-existing anti-NA antibody levels >= 40 were associated with a 69% (95% confidence interval [CI], 34-85%) shortened shedding duration (mean, 1.0 vs 3.2 days). Neuraminidase antibody levels >= 80 were associated with further shortened shedding and significantly shortened symptom duration (influenza-like illness, 82%; 95% CI, 39-95%). Among RT-PCR-confirmed infections in children, hemagglutination inhibition titers >= 1:20 were associated with a 32% (95% CI, 13-47%) shortened shedding duration (mean, 3.9 vs 6.0 days).Conclusions. Our results suggest that anti-NA antibodies play a large role in reducing influenza illness duration in adults and may impact transmission, most clearly among adults. Neuraminidase should be considered as an additional target in next-generation influenza virus vaccine development.