Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA.
Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL 34987, USA.
Viruses. 2023 Jan 11;15(1):203. doi: 10.3390/v15010203.
Initial exposure to influenza virus(es) during early childhood produces protective antibodies that may be recalled following future exposure to subsequent viral infections or vaccinations. Most influenza vaccine research studies use immunologically naïve animal models to assess vaccine effectiveness. However, most people have an extensive influenza immune history, with memory cells produced by viruses or vaccines representing multiple influenza viruses. In this study, we explored the effect influenza seasonal virus-induced immunity has on pre-pandemic influenza virus vaccination. The mice that were pre-immune to historical H1N1 and H3N2 seasonal influenza viruses were vaccinated with adjuvanted pre-pandemic (H2, H5, and H7) HA-based computationally optimized broadly reactive antigen (COBRA) vaccines, and were fully protected from lethal challenge, whereas the mock-vaccinated mice, with or without pre-immunity, were not protected from morbidity or mortality. Detectable antibody titers were present in the pre-immune mice vaccinated with a single dose of vaccine, but not in the immunologically naïve mice. The mice vaccinated twice with the trivalent COBRA HA vaccine had similar antibody titers regardless of their pre-immune status. Overall, seasonal pre-immunity did not interfere with the immune responses elicited by pre-pandemic COBRA HA vaccines or the protection against pre-pandemic viruses.
初次接触流感病毒会产生保护性抗体，这些抗体可能会在未来再次接触到其他病毒感染或接种疫苗时被重新激活。大多数流感疫苗研究使用免疫原性未被激活的动物模型来评估疫苗的有效性。然而，大多数人都有广泛的流感免疫史，记忆细胞由病毒或疫苗产生，代表了多种流感病毒。在这项研究中，我们探讨了季节性流感病毒诱导的免疫对大流行前流感病毒疫苗接种的影响。预先对历史 H1N1 和 H3N2 季节性流感病毒具有免疫力的小鼠用佐剂增强的大流行前（H2、H5 和 H7）基于 HA 的计算优化的广泛反应性抗原（COBRA）疫苗进行了接种，并且完全免受致死性挑战的侵害，而未经模拟接种的小鼠，无论是否具有预先免疫力，都无法免受发病率或死亡率的影响。在接种一剂疫苗的预先免疫小鼠中可检测到抗体滴度，但在免疫原性未被激活的小鼠中则无法检测到。两次接种三价 COBRA HA 疫苗的小鼠，无论其预先免疫状态如何，抗体滴度相似。总体而言，季节性预先免疫不会干扰大流行前 COBRA HA 疫苗引发的免疫反应，也不会影响对大流行前病毒的保护作用。
