Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, Illinois, USA
Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, Illinois, USA.
J Virol. 2019 Oct 15;93(21). doi: 10.1128/JVI.01150-19. Print 2019 Nov 1.
Vaccination is the best measure of protection against influenza virus infection. Vaccine-induced antibody responses target mainly the hemagglutinin (HA) surface glycoprotein, composed of the head and the stalk domains. Recently two novel vaccine platforms have been developed for seasonal influenza vaccination: a recombinant HA vaccine produced in insect cells (Flublok) and Flucelvax, prepared from virions produced in mammalian cells. In order to compare the fine specificity of the antibodies induced by these two novel vaccine platforms, we characterized 42 Flublok-induced monoclonal antibodies (MAbs) and 38 Flucelvax-induced MAbs for avidity, cross-reactivity, and any selectivity toward the head versus the stalk domain. These studies revealed that Flublok induced a greater proportion of MAbs targeting epitopes near the receptor-binding domain on HA head (hemagglutinin inhibition-positive MAbs) than Flucelvax, while the two vaccines induced similar low frequencies of stalk-reactive MAbs. Finally, mice immunized with Flublok and Flucelvax also induced similar frequencies of stalk-reactive antibody-secreting cells, showing that HA head immunodominance is independent of immune memory bias. Collectively, our results suggest that these vaccine formulations are similarly immunogenic but differ in the preferences of the elicited antibodies toward the receptor-binding domain on the HA head. There are ongoing efforts to increase the efficacy of influenza vaccines and to promote production strategies that can rapidly respond to newly emerging viruses. It is important to understand if current alternative seasonal vaccines, such as Flublok and Flucelvax, that use alternate production strategies can induce protective influenza-specific antibodies and to evaluate what type of epitopes are targeted by distinct vaccine formulations.
接种疫苗是预防流感病毒感染的最佳措施。疫苗诱导的抗体反应主要针对血凝素（HA）表面糖蛋白，由头部和茎部组成。最近，两种新型流感疫苗平台已被开发用于季节性流感疫苗接种：一种在昆虫细胞中生产的重组 HA 疫苗（Flublok）和由哺乳动物细胞中产生的病毒粒子制备的 Flucelvax。为了比较这两种新型疫苗平台诱导的抗体的精细特异性，我们对 42 株 Flublok 诱导的单克隆抗体（MAb）和 38 株 Flucelvax 诱导的 MAb 进行了鉴定，以评估其亲和力、交叉反应性以及对头部与茎部的选择性。这些研究表明，Flublok 诱导的针对 HA 头部受体结合域附近表位的抗体（血凝素抑制阳性 MAb）比例大于 Flucelvax，而这两种疫苗诱导的茎反应性 MAb 比例相似。最后，用 Flublok 和 Flucelvax 免疫的小鼠也诱导了相似频率的茎反应性抗体分泌细胞，表明 HA 头部免疫优势独立于免疫记忆偏倚。总之，我们的结果表明，这些疫苗制剂具有相似的免疫原性，但诱导的抗体对 HA 头部受体结合域的偏好不同。目前正在努力提高流感疫苗的疗效，并促进能够快速应对新出现病毒的生产策略。了解当前使用替代生产策略的替代季节性疫苗（如 Flublok 和 Flucelvax）是否能诱导保护性流感特异性抗体，并评估不同疫苗制剂所针对的表位类型非常重要。
