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An influenza A virus (H7N9) anti-neuraminidase monoclonal antibody protects mice from morbidity without interfering with the development of protective immunity to subsequent homologous challenge
Virology ( IF 2.8 ) Pub Date : 2017-09-06 , DOI: 10.1016/j.virol.2017.08.016
Jason R. Wilson , Jessica A. Belser , Juliana DaSilva , Zhu Guo , Xiangjie Sun , Shane Gansebom , Yaohui Bai , Thomas J. Stark , Jessie Chang , Paul Carney , Min Z. Levine , John Barnes , James Stevens , Taronna R. Maines , Terrence M. Tumpey , Ian A. York

The emergence of A(H7N9) virus strains with resistance to neuraminidase (NA) inhibitors highlights a critical need to discover new countermeasures for treatment of A(H7N9) virus-infected patients. We previously described an anti-NA mAb (3c10-3) that has prophylactic and therapeutic efficacy in mice lethally challenged with A(H7N9) virus when delivered intraperitoneally (i.p.). Here we show that intrananasal (i.n.) administration of 3c10-3 protects 100% of mice from mortality when treated 24 h post-challenge and further characterize the protective efficacy of 3c10-3 using a nonlethal A(H7N9) challenge model. Administration of 3c10-3 i.p. 24 h prior to challenge resulted in a significant decrease in viral lung titers and deep sequencing analysis indicated that treatment did not consistently select for viral variants in NA. Furthermore, prophylactic administration of 3c10-3 did not inhibit the development of protective immunity to subsequent homologous virus re-challenge. Taken together, 3c10-3 highlights the potential use of anti-NA mAb to mitigate influenza virus infection.



中文翻译:

甲型流感病毒(H7N9)抗神经氨酸酶单克隆抗体可保护小鼠免受疾病侵袭,而不会干扰对随后同源攻击的保护性免疫的发展

对神经氨酸酶(NA)抑制剂有抗药性的A(H7N9)病毒株的出现突出表明,迫切需要发现治疗A(H7N9)病毒感染患者的新对策。我们先前描述了一种抗NA mAb(3c10-3),在腹膜内(ip)递送时,在致命感染A(H7N9)病毒的小鼠中具有预防和治疗功效。在这里,我们显示经鼻内给药3c10-3(在攻击后24小时进行治疗)可保护100%的小鼠免于死亡,并使用非致命性A(H7N9)攻击模型进一步表征3c10-3的保护功效。攻击前24 h腹膜内3c1​​0-3 ip给药导致病毒肺滴度显着降低,深度测序分析表明治疗并不能始终如一地选择NA中的病毒变体。此外,预防性给予3c10-3不会抑制对随后的同源病毒再次攻击的保护性免疫的发展。综上所述,3c10-3强调了抗NA mAb缓解流感病毒感染的潜在用途。

更新日期:2017-09-06
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