Monoclonal Antibody Technology Core

摘要 提高新型流感疫苗诱导的抗体反应的持久性和有效性；以及 研制新型抗流感治疗试剂是流感研究的中心目标。一款更耐用的 流感疫苗和广谱疗法对预防突变和新型流感很重要 导致年度感染和大流行的流感菌株。单抗(MAbbs)提供了 在我们的思想和设计更广泛的保护性疫苗方面以及作为潜在的广泛的 抗流感药物的光谱。虽然血凝素(HA)仍然是疫苗或 治疗靶点、神经氨酸酶(NA)抗体和其他流感蛋白的研究要少得多，但 也具有保护性，可能会与更广泛的流感病毒株结合。在这个项目的各个项目中 抗流感病毒HA、NA、基质蛋白(M1)和核蛋白(NP)的单抗将用于识别表位， 评估已知和新的表位的保护广度和效力，了解新的机制 保护，并评估试验疫苗的效力。因此，该计划中的四个项目将使用mAb核心 作为中心资源，以便为抗原和疫苗设计提供信息。此外，拟议的研究将 产生大量单抗，这些单抗本身可能作为治疗流感的治疗试剂很有价值 感染。为此，我们将从我们优先确定的新队列中产生抗体 在HA上以保守表位为靶标，而在其他表位上以更高的频率靶向保守表位 流感蛋白包括NA、NP和M1。核心项目还将帮助这些项目评估试验疫苗的效力。 以及在单抗水平上的特异性。

Summary Improving the durability and efficacy of the antibody response induced by novel influenza vaccines, and generating novel anti-influenza therapeutic reagents are central goals of influenza research. A more durable influenza vaccine and broad-spectrum therapeutics are important for protection against mutant and novel influenza strains that cause annual infection and pandemics. Monoclonal antibodies (mAbs) have provided major advances both in our thinking and for design of more broadly-protective vaccines and as potential broad- spectrum anti-influenza therapeutics. While hemagglutinin (HA) remains a mainstay as a vaccine or therapeutic target, antibodies to neuraminidase (NA) and other influenza proteins are much less studied but are also protective and may bind a wider range of influenza strains. In the various projects of this program mAbs against influenza HA, NA, matrix protein (M1) and nuclear protein (NP) will be used to identify epitopes, to evaluate known and novel epitopes for breadth and potency of protection, to learn new mechanisms of protection, and to evaluate trial vaccine efficacy. Thus the four projects in this program will use the mAb core as a central resource in order to inform on antigen and vaccine design. Further, the studies proposed will generate large panels of mAbs that may themselves be valuable as therapeutic reagents to treat influenza infections. For this we will produce antibodies from novel cohorts that we have identified that preferentially target conserved epitopes on HA, and at substantially greater frequencies to conserved epitopes on other influenza proteins including NA, NP and M1. The core will also help the projects evaluate trial vaccine efficacy and specificity at the monoclonal antibody level.