Influenza virus outbreaks are a major burden worldwide each year. Current vaccination strategies are inadequate due to antigenic drift/shift of the virus and the elicitation of low immune responses. The use of computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) immunogens subvert the constantly mutating viruses; however, they are poorly immunogenic on their own. To increase the immunogenicity of subunit vaccines such as this, adjuvants can be delivered with the vaccine. For example, agonists of the stimulator of interferon genes (STING) have proven efficacy as vaccine adjuvants. However, their use in high-risk populations most vulnerable to influenza virus infection has not been closely examined. Here, we utilize a vaccine platform consisting of acetalated dextran microparticles loaded with COBRA HA and the STING agonist cyclic GMP-AMP. We examine the immunogenicity of this platform in mouse models of obesity, aging, and chemotherapy-induced immunosuppression. Further, we examine vaccine efficacy in collaborative cross mice, a genetically diverse population that mimics human genetic heterogeneity. Overall, this vaccine platform had variable efficacy in these populations supporting work to better tailor adjuvants to specific populations.

中文翻译：

---

佐剂广泛活性流感疫苗在免疫功能低下和不同人群中的免疫原性

流感病毒的爆发每年都是全世界的一个重大负担。由于病毒的抗原漂移/转移和引发低免疫反应，目前的疫苗接种策略是不够的。使用经过计算优化的广泛反应抗原（COBRA）血凝素（HA）免疫原颠覆不断变异的病毒；然而，它们本身的免疫原性很差。为了增加此类亚单位疫苗的免疫原性，可以将佐剂与疫苗一起递送。例如，干扰素基因刺激剂 (STING) 的激动剂已被证明作为疫苗佐剂的功效。然而，它们在最容易感染流感病毒的高危人群中的使用尚未得到仔细研究。在这里，我们利用了一个疫苗平台，该平台由负载有 COBRA HA 和 STING 激动剂环 GMP-AMP 的乙醛化葡聚糖微粒组成。我们在肥胖、衰老和化疗引起的免疫抑制小鼠模型中检查了该平台的免疫原性。此外，我们还研究了协作杂交小鼠的疫苗功效，这是一个模仿人类遗传异质性的遗传多样性群体。总体而言，该疫苗平台在这些人群中具有不同的功效，支持更好地针对特定人群定制佐剂的工作。