Center for Inflammation, Immunity &Infection, Institute for Biomedical Sciences, Georgia State University, 100 Piedmont Ave SE, Atlanta, GA 30303, USA.
Department of Microbiology &Immunology, School of Medicine Emory University, 1518 Clifton Road, Atlanta, GA 30322, USA.
Sci Rep. 2017 Jan 9;7:40226. doi: 10.1038/srep40226.
Influenza virus is a significant cause of morbidity and mortality, with worldwide seasonal epidemics. The duration and quality of humoral immunity and generation of immunological memory to vaccines is critical for protective immunity. In the current study, we examined the long-lasting protective efficacy of chimeric VLPs (cVLPs) containing influenza HA and GPI-anchored CCL28 as antigen and mucosal adjuvant, respectively, when immunized intranasally in mice. We report that the cVLPs induced significantly higher and sustainable levels of virus-specific antibody responses, especially IgA levels and hemagglutination inhibition (HAI) titers, more than 8-month post-vaccination compared to influenza VLPs without CCL28 or influenza VLPs physically mixed with sCCL28 (soluble) in mice. After challenging the vaccinated animals at month 8 with H3N2 viruses, the cVLP group also demonstrated strong recall responses. On day 4 post-challenge, we measured increased antibody levels, ASCs and HAI titers with reduced viral load and inflammatory responses in the cVLP group. The animals vaccinated with the cVLP showed 20% cross-protection against drifted (Philippines) and 60% protection against homologous (Aichi) H3N2 viruses. Thus, the results suggest that the GPI-anchored CCL28 induces significantly higher mucosal antibody responses, involved in providing long-term cross-protection against H3N2 influenza virus when compared to other vaccination groups.
流感病毒是发病率和死亡率的重要原因，具有全球性的季节性流行。体液免疫的持续时间和质量以及疫苗产生免疫记忆对于保护性免疫至关重要。在本研究中，我们研究了分别包含流感血凝素（HA）和糖基化磷脂酰肌醇锚定的趋化因子 28（CCL28）作为抗原和黏膜佐剂的嵌合 VLPs（cVLPs）在小鼠中鼻内免疫的长期保护效果。我们报告说，与不含 CCL28 的流感 VLPs 或流感 VLPs 与可溶性 CCL28（sCCL28）物理混合相比，cVLPs 诱导了更高且可持续的病毒特异性抗体反应，特别是 IgA 水平和血凝抑制（HAI）滴度，在接种疫苗后 8 个月以上。在 8 个月后用 H3N2 病毒对接种动物进行攻毒后，cVLP 组也表现出强烈的回忆反应。在攻毒后第 4 天，我们测量了抗体水平、ASCs 和 HAI 滴度的增加，同时在 cVLP 组中降低了病毒载量和炎症反应。接种 cVLP 的动物对漂移（菲律宾）株显示出 20%的交叉保护作用，对同源（Aichi）H3N2 病毒的保护作用为 60%。因此，结果表明，与其他接种组相比，糖基化磷脂酰肌醇锚定的 CCL28 诱导了更高的黏膜抗体反应，参与提供针对 H3N2 流感病毒的长期交叉保护作用。
