Single Immunization with Recombinant ACAM2000 Vaccinia Viruses Expressing the Spike and the Nucleocapsid Proteins Protects Hamsters against SARS-CoV-2-Caused Clinical Disease.
Single Immunization with Recombinant ACAM2000 Vaccinia Viruses Expressing the Spike and the Nucleocapsid Proteins Protects Hamsters against SARS-CoV-2-Caused Clinical Disease.
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用表达尖峰的重组ACAM2000疫苗病毒的单一免疫接种，核素蛋白可以保护仓鼠免受SARS-COV-2引起的临床疾病的侵害。
DOI：
10.1128/jvi.00389-22
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发表时间：
2022-05-11
影响因子：
5.4
通讯作者：
中科院分区：
文献类型：
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作者：
目前基于刺突蛋白的COVID-19疫苗免疫导致的SARS-CoV-2突破性感染病例不断增加，这凸显了开发使用不同平台和/或抗原的替代疫苗的必要性。在这项研究中，我们基于新型牛痘病毒（VACV） ACAM2000平台（rACAM2000）表达了SARS-CoV-2刺突蛋白和核衣壳蛋白。在这个平台上，牛痘病毒宿主范围和免疫调节基因E3L被删除，使病毒减毒和增强先天免疫反应，另一个宿主范围基因K3L被痘病毒同源基因TATV037 （TATV037）取代，使病毒在仓鼠和人类细胞中都具有复制能力。在单次肌内免疫后，与在仓鼠模型中表达单个蛋白的rACAM2000相比，共表达刺突蛋白和核衣壳蛋白的rACAM2000对SARS-CoV-2攻击的保护作用显著增强，这表明体重减轻和恢复时间缩短。这种保护作用与降低病毒载量、增加中和抗体滴度和降低中性粒细胞与淋巴细胞的比率有关。因此，我们的研究表明，表达刺突和核衣壳抗原组合的rACAM2000是一种有希望的COVID-19候选疫苗，进一步的研究将探讨rACAM2000候选疫苗是否能诱导对SARS-CoV-2变体感染的持久免疫。当前基于刺突蛋白的COVID-19疫苗诱导的免疫导致突破性感染的SARS-CoV-2变体的不断出现，突出表明需要新一代疫苗，以诱导对广泛变体的持久免疫。为此，我们研究了基于新型VACV ACAM2000平台的重组COVID-19候选疫苗的保护效果，该平台删除了免疫调节基因E3L，并表达了SARS-CoV-2刺突(S)和核衣壳(N)抗原。因此，期望我们构建的候选疫苗具有更高的免疫原性和安全性。在这项工作中描述的初步研究中，我们证明了表达S和N蛋白的候选疫苗在单剂量免疫后保护仓鼠免受SARS-CoV-2攻击方面优于表达单个蛋白（S或N）的构建体，并且进一步研究不同的SARS-CoV-2变体将为未来的临床评估提供依据。
Increasing cases of SARS-CoV-2 breakthrough infections from immunization with current spike protein-based COVID-19 vaccines highlight the need to develop alternative vaccines using different platforms and/or antigens. In this study, we expressed SARS-CoV-2 spike and nucleocapsid proteins based on a novel vaccinia virus (VACV) ACAM2000 platform (rACAM2000). In this platform, the vaccinia virus host range and immunoregulatory gene E3L was deleted to make the virus attenuated and to enhance innate immune responses, and another host range gene, K3L, was replaced with a poxvirus ortholog gene, taterapox virus 037 (TATV037), to make virus replication competent in both hamster and human cells. Following a single intramuscular immunization, the rACAM2000 coexpressing the spike and nucleocapsid proteins induced significantly improved protection against SARS-CoV-2 challenge in comparison to rACAM2000 expressing the individual proteins in a hamster model, as shown by reduced weight loss and shorter recovery time. The protection was associated with reduced viral loads, increased neutralizing antibody titer, and reduced neutrophil-to-lymphocyte ratio. Thus, our study demonstrates that rACAM2000 expressing a combination of the spike and nucleocapsid antigens is a promising COVID-19 vaccine candidate, and further studies will investigate if the rACAM2000 vaccine candidate can induce a long-lasting immunity against infection by SARS-CoV-2 variants of concern. IMPORTANCE Continuous emergence of SARS-CoV-2 variants which cause breakthrough infection from the immunity induced by current spike protein-based COVID-19 vaccines highlights the need for new generations of vaccines that will induce long-lasting immunity against a wide range of the variants. To this end, we investigated the protective efficacy of the recombinant COVID-19 vaccine candidates based on a novel VACV ACAM2000 platform, in which an immunoregulatory gene, E3L, was deleted and both the SARS-CoV-2 spike (S) and nucleocapsid (N) antigens were expressed. Thus, it is expected that the vaccine candidate we constructed should be more immunogenic and safer. In the initial study described in this work, we demonstrated that the vaccine candidate expressing both the S and N proteins is superior to the constructs expressing an individual protein (S or N) in protecting hamsters against SARS-CoV-2 challenge after a single-dose immunization, and further investigation against different SARS-CoV-2 variants will warrant future clinical evaluations.
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影响因子：
9.2
作者：
Chiuppesi F;Nguyen VH;Park Y;Contreras H;Karpinski V;Faircloth K;Nguyen J;Kha M;Johnson D;Martinez J;Iniguez A;Zhou Q;Kaltcheva T;Frankel P;Kar S;Sharma A;Andersen H;Lewis MG;Shostak Y;Wussow F;Diamond DJ
通讯作者：
Diamond DJ
影响因子：
5.5
作者：
Guebre-Xabier M;Patel N;Tian JH;Zhou B;Maciejewski S;Lam K;Portnoff AD;Massare MJ;Frieman MB;Piedra PA;Ellingsworth L;Glenn G;Smith G
通讯作者：
Smith G
影响因子：
64.5
作者：
Hoffmann M;Arora P;Groß R;Seidel A;Hörnich BF;Hahn AS;Krüger N;Graichen L;Hofmann-Winkler H;Kempf A;Winkler MS;Schulz S;Jäck HM;Jahrsdörfer B;Schrezenmeier H;Müller M;Kleger A;Münch J;Pöhlmann S
通讯作者：
Pöhlmann S
影响因子：
1.9
作者：
Cao, Jingxin;Layne, Christine;Deschambault, Yvon
通讯作者：
Deschambault, Yvon
影响因子：
5.5
作者：
Cottingham, Matthew G.;Carroll, Miles W.
通讯作者：
Carroll, Miles W.