Antibody to Influenza Virus Neuraminidase: An Independent Correlate of Protection

Antibody to Influenza Virus Neuraminidase: An Independent Correlate of Protection
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DOI:
10.1093/infdis/jiv195
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发表时间:
2015-10-15
影响因子:
6.4
通讯作者:
Ohmit, Suzanne E.
Ohmit, Suzanne E.
中科院分区:
医学2区
文献类型:
--
作者:
Monto, Arnold S.;Petrie, Joshua G.;Ohmit, Suzanne E.

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背景流感疫苗保护的实验室相关性最好通过检查尽管接种疫苗但仍被感染的人来确定。虽然抗病毒血凝素(HA)抗体的重要性早已被认识到,但抗病毒神经氨酸酶(NA)抗体独立贡献的保护水平尚未确定。采用血凝抑制试验(HAI)、微量中和试验(MN)和新标准化的凝集素神经氨酸酶抑制试验(NAI)检测流感灭活疫苗(IIV)和流感减毒活疫苗(LAIV)的血清。NAI试验检测到37%的IIV接种者有疫苗应答,而HAI和MN试验分别检测到77%和67%的参与者有疫苗应答。对于LAIV受体,NAI、HAI和MN检测分别检测到6%、21%和17%的应答。在IIV受体中,随着NAI测定滴度升高,感染频率下降,与HAI和MN测定观察到的模式相似。HAI和MN测定滴度高度相关,但NAI测定滴度表现出较小的相关性。分析表明NAI抗体在保护中的独立作用,这在IIV、LAIV和安慰剂组中是相似的。虽然NAI抗体在很大程度上不是响应于电流IIV而产生的,但它似乎具有独立的保护作用。随着新流感疫苗的开发,应考虑NA含量。
Background. Laboratory correlates of influenza vaccine protection can best be identified by examining people who are infected despite vaccination. While the importance of antibody to viral hemagglutinin (HA) has long been recognized, the level of protection contributed independently by antibody to viral neuraminidase (NA) has not been determined.Methods. Sera from a controlled trial of the efficacies of inactivated influenza vaccine (IIV) and live attenuated influenza vaccine (LAIV) were tested by hemagglutination inhibition (HAI) assay, microneutralization (MN) assay, and a newly standardized lectin-based neuraminidase inhibition (NAI) assay.Results. The NAI assay detected a vaccine response in 37% of IIV recipients, compared with 77% and 67% of participants in whom responses were detected by the HAI and MN assays, respectively. For LAIV recipients, the NAI, HAI, and MN assays detected responses in 6%, 21%, and 17%, respectively. In IIV recipients, as NAI assay titers rose, the frequency of infection fell, similar to patterns seen with HAI and MN assays. HAI and MN assay titers were highly correlated, but NAI assay titers exhibited less of a correlation. Analyses suggested an independent role for NAI antibody in protection, which was similar in the IIV, LAIV, and placebo groups.Conclusions. While NAI antibody is not produced to a large extent in response to current IIV, it appears to have an independent role in protection. As new influenza vaccines are developed, NA content should be considered.