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转染色体牛来源的广谱中和抗体作为强大的生物治疗药物,可有效应对重要新兴病毒病原体,特别关注 SARS-CoV-2、MERS-CoV、埃博拉病毒、寨卡病毒、HIV-1 和甲型流感病毒。

Transchromosomic bovines-derived broadly neutralizing antibodies as potent biotherapeutics to counter important emerging viral pathogens with a special focus on SARS-CoV-2, MERS-CoV, Ebola, Zika, HIV-1, and influenza A virus.

机构信息

National Food Safety Authority (NFSA), Aswan, Egypt.

Ministry of Tourism and Antiquities, Aswan, Egypt.

出版信息

J Med Virol. 2022 Oct;94(10):4599-4610. doi: 10.1002/jmv.27907. Epub 2022 Jun 11.

Abstract

Historically, passive immunotherapy is an approved approach for protecting and treating humans against various diseases when other alternative therapeutic options are unavailable. Human polyclonal antibodies (hpAbs) can be made from convalescent human donor serum, although it is considered limited due to pandemics and the urgent requirement. Additionally, polyclonal antibodies (pAbs) could be generated from animals, but they may cause severe immunoreactivity and, once "humanized," may have lower neutralization efficiency. Transchromosomic bovines (TcBs) have been developed to address these concerns by creating robust neutralizing hpAbs, which are useful in preventing and/or curing human infections in response to hyperimmunization with vaccines holding adjuvants and/or immune stimulators over an extensive period. Unlike other animal-derived pAbs, potent hpAbs could be promptly produced from TcB in large amounts to assist against an outbreak scenario. Some of these highly efficacious TcB-derived antibodies have already neutralized and blocked diseases in clinical studies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has numerous variants classified into variants of concern (VOCs), variants of interest (VOIs), and variants under monitoring. Although these variants possess different mutations, such as N501Y, E484K, K417N, K417T, L452R, T478K, and P681R, SAB-185 has shown broad neutralizing activity against VOCs, such as Alpha, Beta, Gamma, Delta, and Omicron variants, and VOIs, such as Epsilon, Iota, Kappa, and Lambda variants. This article highlights recent developments in the field of bovine-derived biotherapeutics, which are seen as a practical platform for developing safe and effective antivirals with broad activity, particularly considering emerging viral infections such as SARS-CoV-2, Ebola, Middle East respiratory syndrome coronavirus, Zika, human immunodeficiency virus type 1, and influenza A virus. Antibodies in the bovine serum or colostrum, which have been proved to be more protective than their human counterparts, are also reviewed.

摘要

从历史上看,当其他治疗选择不可用时,被动免疫疗法是一种被批准的保护和治疗人类免受各种疾病的方法。人多克隆抗体(hpAbs)可以从康复的人类供体血清中制备,尽管由于大流行和紧急需求,它被认为是有限的。此外,多克隆抗体(pAbs)可以从动物中产生,但它们可能引起严重的免疫反应,并且一旦“人源化”,可能具有较低的中和效率。转染色体牛(TcBs)的开发是为了解决这些问题,通过产生强大的中和 hpAbs,这些抗体在广泛的时间内通过用含有佐剂和/或免疫刺激剂的疫苗进行超免疫接种,可用于预防和/或治疗人类感染。与其他动物来源的 pAbs 不同,大量的 TcB 可以迅速产生有效的 hpAbs 来帮助应对疫情爆发。这些高效的 TcB 衍生抗体中的一些已经在临床研究中中和和阻断了疾病。严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)有许多变体被分类为关注变体(VOCs)、感兴趣变体(VOIs)和监测变体。尽管这些变体具有不同的突变,如 N501Y、E484K、K417N、K417T、L452R、T478K 和 P681R,但 SAB-185 对 VOCs,如 Alpha、Beta、Gamma、Delta 和 Omicron 变体,以及 VOIs,如 Epsilon、Iota、Kappa 和 Lambda 变体,具有广泛的中和活性。本文重点介绍了牛源生物疗法领域的最新进展,该领域被视为开发具有广泛活性的安全有效的抗病毒药物的实用平台,特别是考虑到 SARS-CoV-2、埃博拉、中东呼吸综合征冠状病毒、寨卡、人类免疫缺陷病毒 1 和甲型流感病毒等新兴病毒感染。还回顾了牛血清或初乳中已被证明比其人类对应物更具保护性的抗体。

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