Although seasonal influenza vaccines block most predominant influenza types and subtypes, humans still remain vulnerable to waves of seasonal and new potential pandemic influenza viruses for which no immunity may exist because of viral antigenic drift and/or shift. Previously, we described a human monoclonal antibody (hMAb), KPF1, which was produced in human embryonic kidney 293T cells (KPF1-HEK) with broad and potent neutralizing activity against H1N1 influenza A viruses (IAV) in vitro, and prophylactic and therapeutic activities in vivo. In this study, we produced hMAb KPF1 in tobacco plants (KPF1-Antx) and demonstrated how the plant-produced KPF1-Antx hMAb possesses similar biological activity compared with the mammalian-produced KPF1-HEK hMAb. KPF1-Antx hMAb showed broad binding to recombinant HA proteins and H1N1 IAV, including A/California/04/2009 (pH1N1) in vitro, which was comparable to that observed with KPF1-HEK hMAb. Importantly, prophylactic administration of KPF1-Antx hMAb to guinea pigs prevented pH1N1 infection and transmission in both prophylactic and therapeutic experiments, substantiating its clinical potential to prevent and treat H1N1 infections. Collectively, this study demonstrated, for the first time, a plant-produced influenza hMAb with in vitro and in vivo activity against influenza virus. Because of the many advantages of plant-produced hMAbs, such as rapid batch production, low cost, and the absence of mammalian cell products, they represent an alternative strategy for the production of immunotherapeutics for the treatment of influenza viral infections, including emerging seasonal and/or pandemic strains.

译文

:尽管季节性流感疫苗可以阻断大多数主要的流感类型和亚型,但人类仍然容易受到季节性和新的潜在大流行性流感病毒浪潮的影响,由于病毒抗原的漂移和/或转移,它们可能没有免疫力。以前,我们描述了一种人单克隆抗体(hMAb)KPF1,它在人胚肾293T细胞(KPF1-HEK)中产生,在体外对H1N1甲型流感病毒(IAV)具有广泛而有效的中和活性,并具有预防和治疗作用体内。在这项研究中,我们在烟草植物(KPF1-Antx)中生产了hMAb KPF1,并证明了与哺乳动物生产的KPF1-HEK hMAb相比,植物生产的KPF1-Antx hMAb具有相似的生物学活性。 KPF1-Antx hMAb在体外显示出与重组HA蛋白和H1N1 IAV的广泛结合,包括A / California / 04/2009(pH1N1),与KPF1-HEK hMAb观察到的相当。重要的是,在预防性和治疗性实验中,对豚鼠进行预防性施用KPF1-Antx hMAb可以预防pH1N1感染和传播,从而证实了其预防和治疗H1N1感染的临床潜力。总的来说,这项研究首次证明了植物产生的对人流感病毒具有体外和体内活性的hMAb流感病毒。由于植物产生的hMAb具有许多优势,例如批量生产迅速,成本低廉,并且不存在哺乳动物细胞产物,因此它们代表了生产用于治疗流感病毒感染的免疫疗法的替代策略,包括出现季节性和季节性流感病毒。 /或大流行毒株。

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