Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Clin Infect Dis. 2020 May 23;70(11):2290-2297. doi: 10.1093/cid/ciz639.
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.
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.
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).
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.We found that antibodies against neuraminidase were associated with significantly shortened viral shedding, and among adults they were also associated with shortened symptom duration. These results support neuraminidase as a potential target of next-generation influenza virus vaccines.
流感在全球造成了巨大负担，而目前的季节性流感疫苗效果并不理想。为了开发更好、更广泛保护的疫苗，我们需要更深入地了解针对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。
我们使用了一项在尼加拉瓜马那瓜进行的基于社区的家庭流感病毒传播病例确定研究。利用 170 例逆转录-聚合酶链反应（RT-PCR）确诊的甲型 H1N1pdm 流感病毒感染和 45 例血清学确诊感染的家庭成员的数据，我们使用加速失效时间模型检查了预先存在的 NA、血凝抑制和 HA 茎部抗体水平与流感病毒脱落和疾病持续时间的关联。
在成人中，RT-PCR 确诊的感染中，预先存在的抗-NA 抗体水平≥40 与脱落持续时间缩短 69%（95%置信区间[CI]，34-85%）相关（平均，1.0 天与 3.2 天）。神经氨酸酶抗体水平≥80 与脱落进一步缩短和症状持续时间显著缩短相关（流感样疾病，82%；95%CI，39-95%）。在儿童中，RT-PCR 确诊的感染中，血凝抑制滴度≥1:20 与脱落持续时间缩短 32%（95%CI，13-47%）相关（平均，3.9 天与 6.0 天）。
我们的结果表明，抗-NA 抗体在缩短成人流感疾病持续时间方面发挥了重要作用，并且可能在传播中发挥作用，在成人中最为明显。神经氨酸酶应被视为下一代流感病毒疫苗开发的另一个目标。我们发现，抗神经氨酸酶抗体与病毒脱落显著缩短相关，在成人中也与症状持续时间缩短相关。这些结果支持神经氨酸酶作为下一代流感病毒疫苗的潜在目标。
