Short-Term Instantaneous Prophylaxis and Efficient Treatment Against SARS-CoV-2 in hACE2 Mice Conferred by an Intranasal Nanobody (Nb22).
Short-Term Instantaneous Prophylaxis and Efficient Treatment Against SARS-CoV-2 in hACE2 Mice Conferred by an Intranasal Nanobody (Nb22).
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DOI：
10.3389/fimmu.2022.865401
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发表时间：
2022
影响因子：
7.3
通讯作者：
Wu Z
中科院分区：
文献类型：
--
作者：
Wu X;Wang Y;Cheng L;Ni F;Zhu L;Ma S;Huang B;Ji M;Hu H;Li Y;Xu S;Shi H;Zhang D;Liu L;Nawaz W;Hu Q;Ye S;Liu Y;Wu Z
目前的COVID-19疫苗需要至少一个月的时间才能完成接种，然后才能生效。全球约51%的人口尚未完全接种疫苗。即时保护是那些没有完全接种疫苗的人的一个未得到满足的需求。此外，由SARS-CoV-2引起的突破性感染被广泛报道。所有这些都突出表明，在SARS-CoV-2流行的社区，短期即时预防（STIP）的需求没有得到满足。此前，我们报道了从用刺突蛋白免疫的羊驼中分离的纳米抗体，其表现出抗SARS-CoV-2及其变体的免疫效力。在此，我们发现，在我们先前报道的纳米抗体中，Nb 22表现出对Delta变体的超有效中和，其IC 50值为0.41 ng/ml（5.13 pM）。晶体结构分析表明，Nb 22与WH 01和Delta RBD的结合均有效地阻断了RBD与hACE 2的结合。此外，鼻内Nb 22在暴露后预防（PEP）和暴露前预防（PrEP）中表现出对SARS-CoV-2 Delta变体的保护作用。值得注意的是，鼻内Nb 22也表现出对STIP中SARS-CoV-2 Delta变体的高效力，通过单剂量施用持续7天，并且通过四剂量施用在呼吸系统中表现出持久保留至少一个月，提供了针对SARS-CoV-2的瞬时短期预防策略。因此，鼻内或吸入的Nb 22的抗病毒效力、在呼吸系统中的持久保留和在室温下的稳定性使得其成为抗SARS-CoV-2的潜在治疗剂或STIP剂。
Current COVID-19 vaccines need to take at least one month to complete inoculation and then become effective. Around 51% of the global population is still not fully vaccinated. Instantaneous protection is an unmet need among those who are not fully vaccinated. In addition, breakthrough infections caused by SARS-CoV-2 are widely reported. All these highlight the unmet needing for short-term instantaneous prophylaxis (STIP) in the communities where SARS-CoV-2 is circulating. Previously, we reported nanobodies isolated from an alpaca immunized with the spike protein, exhibiting ultrahigh potency against SARS-CoV-2 and its variants. Herein, we found that Nb22, among our previously reported nanobodies, exhibited ultrapotent neutralization against Delta variant with an IC50 value of 0.41 ng/ml (5.13 pM). Furthermore, the crystal structural analysis revealed that the binding of Nb22 to WH01 and Delta RBDs both effectively blocked the binding of RBD to hACE2. Additionally, intranasal Nb22 exhibited protection against SARS-CoV-2 Delta variant in the post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP). Of note, intranasal Nb22 also demonstrated high efficacy against SARS-CoV-2 Delta variant in STIP for seven days administered by single dose and exhibited long-lasting retention in the respiratory system for at least one month administered by four doses, providing a strategy of instantaneous short-term prophylaxis against SARS-CoV-2. Thus, ultrahigh potency, long-lasting retention in the respiratory system and stability at room-temperature make the intranasal or inhaled Nb22 to be a potential therapeutic or STIP agent against SARS-CoV-2.
具有局部治疗 HPV18 相关宫颈癌潜力的强效中和人源化抗体
影响因子：
7.3
作者：
Huang B;Zhu L;Wei H;Shi H;Zhang D;Yuan H;Luan L;Zheng N;Xu S;Nawaz W;Hong Y;Wu X;Wu Z
通讯作者：
Wu Z