Departments of Molecular Virology & Microbiology and Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Vaccine. 2012 Dec 17;31(1):190-5. doi: 10.1016/j.vaccine.2012.10.065. Epub 2012 Oct 26.
Serum antibody to the hemagglutinin (HA) surface protein of influenza virus induced by influenza vaccination is a correlate of protection against influenza. The neuraminidase (NA) protein is also on the surface of the virus; antibody to it has been shown to impair virus release from infected cells and to reduce the intensity of influenza infections in animal models and in humans challenged with infectious virus. Recently we have shown that NA inhibiting antibody can independently contribute to immunity to naturally-occurring influenza immunity in the presence of antibody to the HA.
The present study was conducted to evaluate induction of antibody to the NA and the HA by commercially available influenza vaccines.
Healthy young adults were vaccinated with one of five commercially available trivalent inactivated vaccines or live influenza vaccine. Frequencies of serum antibody and fold geometric mean titer (GMT) increases four weeks later were measured to each of the three vaccine viruses (A/H1N1, A/H3N2, B) in hemagglutination-inhibition (HAI) and neutralization (neut) assays. Frequency and fold GMT increase in neuraminidase-inhibition (NI) antibody titers were measured to the influenza A viruses (A/H1N1, A/H3N2).
No significant reactogenicity occurred among the vaccinated subjects. The Fluvirin inactivated vaccine induced more anti-HA antibody responses and a higher fold GMT increase than the other inactivated vaccines but there were no major differences in response frequencies or fold GMT increase among the inactivated vaccines. Both the frequency of antibody increase and fold GMT increase were significantly lower for live vaccine than for any inactivated vaccine in HAI and neut assays for all three vaccine viruses. Afluria inactivated vaccine induced more N1 antibody and Fluarix induced more N2 antibody than the other vaccines but all inactivated vaccines induced serum NI antibody. The live vaccine failed to elicit any NI responses for the N2 NA of A/H3N2 virus and frequencies were low for the N1 of A/H1N1 virus.
Trivalent inactivated influenza vaccines with similar HA dosage induce similar serum anti-HA antibody responses in healthy adults. Current inactivated vaccines all induce serum anti-NA antibody to the N1 and N2 NA proteins but some are better than others for N1 or N2. The live vaccine, Flumist, was a poor inducer of either anti-HA or anti-NA serum antibody compared to inactivated vaccine in the healthy adults. In view of the capacity for contributing to immunity to influenza in humans, developing guidelines for NA content and induction of NA antibody is desirable.
流感疫苗诱导的针对流感病毒血凝素（HA）表面蛋白的血清抗体是预防流感的相关保护因素。神经氨酸酶（NA）蛋白也存在于病毒表面；已证明针对它的抗体可以破坏感染细胞中病毒的释放，并降低动物模型和感染传染性病毒的人类中流感感染的强度。最近，我们已经证明，在存在针对 HA 的抗体的情况下，NA 抑制抗体可以独立有助于对自然发生的流感免疫的免疫。
本研究旨在评估市售流感疫苗对 NA 和 HA 的诱导作用。
健康的年轻成年人接种了五种市售的三价灭活疫苗或活流感疫苗之一。四周后，通过血凝抑制（HAI）和中和（neut）测定测量针对三种疫苗病毒（A/H1N1、A/H3N2、B）的血清抗体和几何平均滴度（GMT）增加的频率。测量针对流感 A 病毒（A/H1N1、A/H3N2）的神经氨酸酶抑制（NI）抗体滴度的频率和 GMT 增加倍数。
接种疫苗的受试者没有出现明显的不良反应。与其他灭活疫苗相比，Fluvirin 灭活疫苗诱导了更多的抗 HA 抗体反应和更高的 GMT 增加倍数，但在灭活疫苗中，反应频率或 GMT 增加倍数没有明显差异。与任何灭活疫苗相比，活疫苗在 HAI 和 neut 测定中对所有三种疫苗病毒的抗体增加频率和 GMT 增加倍数都显著降低。与其他疫苗相比，Afluria 灭活疫苗诱导了更多的 N1 抗体，Fluarix 诱导了更多的 N2 抗体，但所有灭活疫苗都诱导了血清 NI 抗体。活疫苗未能引起 A/H3N2 病毒 N2 NA 的任何 NI 反应，N1 的频率也很低。
具有相似 HA 剂量的三价灭活流感疫苗在健康成年人中诱导相似的血清抗 HA 抗体反应。目前的灭活疫苗都诱导针对 N1 和 N2 NA 蛋白的血清抗 NA 抗体，但有些比其他的更好用于 N1 或 N2。与灭活疫苗相比，活疫苗 Flumist 在健康成年人中对抗 HA 或抗 NA 血清抗体的诱导能力较差。鉴于其对人类流感免疫的贡献能力，制定关于 NA 含量和 NA 抗体诱导的指南是可取的。
