APP
产业链接
公众号矩阵
动脉智库
活动会议
解决方案
动脉AI
搜索
EN
登录
首页
情报
原创
专题
报告
链接
直播
活动

动脉网APP
扫码下载

一种结合免疫逃逸突变的RBD蛋白疫苗对严重急性呼吸系统综合征冠状病毒2型具有广泛的保护作用

A protein vaccine of RBD integrated with immune evasion mutation shows broad protection against SARS-CoV-2

Nature 等信源发布 2024-11-06 08:00

可切换为仅中文

AbstractVariants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge and evade immunity, resulting in breakthrough infections in vaccinated populations. There is an urgent need for the development of vaccines with broad protective effects. In this study, we selected hotspot mutations in the receptor-binding domain (RBD) that contribute to immune escape properties and integrated them into the original RBD protein to obtain a complex RBD protein (cRBD), and we found cRBDs have broad protective effects against SARS-CoV-2 variants.

摘要严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的变异继续出现并逃避免疫，导致接种疫苗人群出现突破性感染。。在这项研究中，我们选择了受体结合域（RBD）中有助于免疫逃逸特性的热点突变，并将其整合到原始RBD蛋白中以获得复杂的RBD蛋白（cRBD），我们发现cRBD对SARS-CoV-2变体具有广泛的保护作用。

Three cRBDs were designed in our study. Compared with the BA.1 RBD protein, the cRBDs induced the production of higher levels of broader-spectrum neutralizing antibodies, suggesting stronger and broader protective efficacy. In viral challenge experiments, cRBDs were more effective than BA.1 RBD in attenuating lung pathologic injury.

在我们的研究中设计了三个CRBD。与BA.1 RBD蛋白相比，CRBD诱导产生更高水平的广谱中和抗体，表明更强和更广泛的保护功效。在病毒攻击实验中，CRBD在减轻肺病理损伤方面比BA.1 RBD更有效。

Among the three constructs, cRBD3 showed optimal broad-spectrum and protective effects and is a promising candidate for a broad-spectrum SARS-CoV-2 vaccine. In conclusion, immunization with cRBDs triggered immunity against a wide range of variants, including those that emerged after we had completed designing the cRBDs.

在这三种构建体中，cRBD3显示出最佳的广谱和保护作用，是广谱SARS-CoV-2疫苗的有希望的候选者。总之，用CRBD免疫引发了对多种变体的免疫力，包括我们完成CRBD设计后出现的变体。

This study preliminarily explores and validates the feasibility of incorporating hotspot mutations that contribute to immune evasion into the RBD to expand the activity spectrum of antigen-induced antibodies..

这项研究初步探索并验证了将有助于免疫逃避的热点突变纳入RBD以扩大抗原诱导抗体活性谱的可行性。。

IntroductionCoronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly triggered a global public health emergency. According to the WHO, as of January 31, 2024, there were more than 770 million confirmed cases, with more than 77 million confirmed deaths.1 SARS-CoV-2 is an enveloped single-stranded positive-sense RNA virus, which is identical to Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus, belonging to the subgenus of Sarbecovirus.

引言由SARS-CoV-2引起的2019年冠状病毒病（COVID-19）迅速引发了全球公共卫生紧急事件。据世界卫生组织统计，截至2024年1月31日，确诊病例超过7.7亿例，确诊死亡人数超过7700万。1 SARS-CoV-2是一种包膜单链正义RNA病毒，与Sarbecovirus亚属的严重急性呼吸综合征冠状病毒和中东呼吸综合征冠状病毒相同。

The SARS-CoV-2 genome is approximately 30 kb, and the 3′-UTR contains four open reading frames that encode for the generation of structural proteins, including Nucleocapsid, Spike (S), Membrane, and Envelope proteins.2 These structural proteins are responsible for viral particle assembly and are involved in suppressing the host immune response.

SARS-CoV-2基因组约为30kb，3'-UTR包含四个开放阅读框，编码结构蛋白的产生，包括核衣壳，尖峰，膜和包膜蛋白。这些结构蛋白负责病毒颗粒组装，并参与抑制宿主免疫反应。

S is a structural protein of SARS-CoV-2, which composed of two subunits, S1 and S2, and is responsible for target recognition, binding and cell entry of SARS-CoV-2.3 The S1 subunit comprises an N-terminal domain (NTD) and a C-terminal RBD. RBD is responsible for recognizing the angiotensin-converting enzyme 2 receptor (ACE2), thereby mediating SARS-CoV-2 entry.4 The RBD is immunogenic and is the primary target of neutralizing antibodies (nAbs) as well as a favorable antigen for vaccine development.5Continued extensive spread of the virus has resulted in antigenic drift of SARS-CoV-2 genome.

。RBD负责识别血管紧张素转换酶2受体（ACE2），从而介导SARS-CoV-2的进入。RBD具有免疫原性，是中和抗体（NAb）的主要靶标，也是疫苗开发的有利抗原。5病毒的持续广泛传播导致SARS-CoV-2基因组的抗原漂移。

Over time, the high mutation rate of the SARS-CoV-2 genome has resulted in the continual generation of variants, resulting in changes of transmissibility, pathogenicity, and immunological resistance of COVID-19 regionally and globally.6 And SARS-CoV-2 variants such as B.1.1.7、B.1.315、P.1、B.1.617.2 and BA.1.1.529 have been identified as variants of concern (.

随着时间的推移，SARS-CoV-2基因组的高突变率导致变异的不断产生，导致COVID-19在区域和全球的传播性，致病性和免疫抗性发生变化。6和SARS-CoV-2变异，如B.1.1.7，B.1.315，P.1，B.1.617.2和BA.1.1.529已被确定为关注的变异（。

Data availability

数据可用性

All study data are included in the article and/or supplementary information. The original data of mRNA and BCR sequencing in this study is available at GEO under the accession GSE261311 and GSE261313.

所有研究数据均包含在文章和/或补充信息中。本研究中mRNA和BCR测序的原始数据可在GEO获得，登录号为GSE261311和GSE261313。

ReferencesWHO COVID-19 Dashboard. https://covid19.who.int/ (2023).Wang, M.-Y. et al. SARS-CoV-2: structure, biology, and structure-based therapeutics development. Front Cell Infect. Microbiol. 10, 587269 (2020).Article

。https://covid19.who.int/（2023年）。Wang，M.-Y.等。SARS-CoV-2：结构，生物学和基于结构的治疗学发展。前细胞感染。微生物。10587269（2020）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

Magazine, N. et al. Mutations and evolution of the SARS-CoV-2 spike protein. Viruses 14, 640 (2022).Article

杂志，N。等人。SARS-CoV-2尖峰蛋白的突变和进化。病毒14640（2022）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Raghuvamsi, P. V. et al. SARS-CoV-2 S protein: ACE2 interaction reveals novel allosteric targets. eLife 10, 63646 (2021).Article

Raghuvamsi，P.V。等人。SARS-CoV-2 S蛋白：ACE2相互作用揭示了新的变构靶标。eLife 1063646（2021）。文章

Google Scholar

谷歌学者

Dai, L. & Gao, G. F. Viral targets for vaccines against COVID-19. Nat. Rev. Immunol. 21, 73–82 (2021).Article

Dai，L。＆Gao，G.F。针对COVID-19疫苗的病毒靶标。。21，73-82（2021）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Hu, B., Guo, H., Zhou, P. & Shi, Z. L. Characteristics of SARS-CoV-2 and COVID-19. Nat. Rev. Microbiol. 19, 141–154 (2021).Article

Hu，B.，Guo，H.，Zhou，P。＆Shi，Z.L。SARS-CoV-2和COVID-19的特征。自然修订版微生物学。19141-154（2021）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Hattab, D., Amer, M. F. A., Al-Alami, Z. M. & Bakhtiar, A. SARS-CoV-2 journey: from alpha variant to omicron and its sub-variants. Infection 52, 767–786 (2024).Article

Hattab，D.，Amer，M.F.A.，Al-Alami，Z.M。和Bakhtiar，A。SARS-CoV-2旅程：从α变体到omicron及其子变体。感染52767-786（2024）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Garcia-Beltran, W. F. et al. Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. Cell 184, 2523 (2021).Article

Garcia-Beltran，W.F.等人。多种SARS-CoV-2变体通过疫苗诱导的体液免疫逃避中和。细胞1842523（2021）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Hoffmann, M. et al. The Omicron variant is highly resistant against antibody-mediated neutralization: implications for control of the COVID-19 pandemic. Cell 185, 447–456.e411 (2022).Article

Hoffmann，M。等人。Omicron变体对抗体介导的中和具有高度抗性：对控制COVID-19大流行的意义。细胞185447-456.e411（2022）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Andrews, N. et al. Covid-19 vaccine effectiveness against the Omicron (B.1.1.529) variant. N. Engl. J. Med. 386, 1532–1546 (2022).Article

Andrews，N.等人，针对Omicron（B.1.1.529）变体的新型冠状病毒肺炎疫苗的有效性。N、 英语。J、 医学3861532-1546（2022）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Zhao, F., Zai, X., Zhang, Z., Xu, J. & Chen, W. Challenges and developments in universal vaccine design against SARS-CoV-2 variants. NPJ Vaccines 7, 167 (2022).Article

Zhao，F.，Zai，X.，Zhang，Z.，Xu，J。＆Chen，W。针对SARS-CoV-2变体的通用疫苗设计的挑战和发展。NPJ疫苗7167（2022）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Planas, D. et al. Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Nature 602, 671–675 (2022).Article

Planas，D.等人，SARS-CoV-2 Omicron大量逃逸至抗体中和。自然602671-675（2022）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Liu, L. et al. Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2. Nature 602, 676–681 (2022).Article

Liu，L.等人。SARS-CoV-2的Omicron变体表现出惊人的抗体逃避。自然602676-681（2022）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Wang, Q. et al. Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Cell 186, 279–286.e278 (2023).Article

Wang，Q。等人。SARS-CoV-2 BQ和XBB亚型不断上升的惊人抗体逃避特性。细胞186279-286.e278（2023）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Datta, A., Kapre, K., Andi-Lolo, I. & Kapre, S. Multi-valent pneumococcal conjugate vaccine for global health: from problem to platform to production. Hum. Vaccin. Immunother. 18, 2117949 (2022).Article

Datta，A.，Kapre，K.，Andi Lolo，I。＆Kapre，S。全球健康的多价肺炎球菌结合疫苗：从问题到平台再到生产。嗯。疫苗。免疫疗法。182117949（2022）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wang, R. et al. Development of a thermostable SARS-CoV-2 variant-based bivalent protein vaccine with cross-neutralizing potency against Omicron subvariants. Virology 576, 61–68 (2022).Article

Wang，R。等人。开发基于热稳定SARS-CoV-2变体的二价蛋白疫苗，其具有针对Omicron亚变体的交叉中和效力。病毒学576,61-68（2022）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Liang, Y. et al. Design of a mutation-integrated trimeric RBD with broad protection against SARS-CoV-2. Cell Discov. 8, 17 (2022).Article

Liang，Y。等人。突变整合三聚体RBD的设计，具有广泛的抗SARS-CoV-2保护作用。细胞Discov。。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Vita, R. et al. The Immune Epitope Database (IEDB): 2018 update. Nucleic Acids Res. 47, D339–D343 (2019).Article

Vita，R。等人。免疫表位数据库（IEDB）：2018年更新。核酸研究47，D339–D343（2019）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Greaney, A. J. et al. Comprehensive mapping of mutations in the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human plasma antibodies. Cell Host Microbe 29, 463–476.e466 (2021).Article

Greaney，A.J.等人。影响多克隆人血浆抗体识别的SARS-CoV-2受体结合域突变的综合定位。细胞宿主微生物29463-476.e466（2021）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Carabelli, A. M. et al. SARS-CoV-2 variant biology: immune escape, transmission and fitness. Nat. Rev. Microbiol 21, 162–177 (2023).CAS

Carabelli，A.M.等人，《SARS-CoV-2变异生物学：免疫逃逸、传播和适应性》。《自然评论微生物学》21162-177（2023）。中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Starr, T. N. et al. Prospective mapping of viral mutations that escape antibodies used to treat COVID-19. Science 371, 850–854 (2021).Article

Starr，T.N.等人。逃避用于治疗COVID-19的抗体的病毒突变的前瞻性定位。科学371850-854（2021）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Weisblum, Y. et al. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. Elife 9, 61312 (2020).Article

Weisblum，Y.等人通过SARS-CoV-2尖峰蛋白变体逃避中和抗体。Elife 961312（2020）。文章

Google Scholar

谷歌学者

Piccoli, L. et al. Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology. Cell 183, 1024–1042.e1021 (2020).Article

Piccoli，L。等人。通过结构引导的高分辨率血清学绘制SARS-CoV-2尖峰受体结合结构域上的中和和免疫显性位点。细胞1831024-1042.e1021（2020）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Ke, Q. et al. Non-glycosylated SARS-CoV-2 RBD elicited a robust neutralizing antibody response in mice. J. Immunol. Methods 506, 113279 (2022).Article

非糖基化SARS-CoV-2 RBD在小鼠中引发强烈的中和抗体反应。J、 免疫。方法506113279（2022）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Takatsu, K., Kouro, T. & Nagai, Y. Interleukin 5 in the link between the innate and acquired immune response. Adv. Immunol. 101, 191–236 (2009).Article

Takatsu，K.，Kouro，T。＆Nagai，Y。白细胞介素5在先天性和获得性免疫反应之间的联系。高级免疫学。101191-236（2009）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Vazquez, M. I., Catalan-Dibene, J. & Zlotnik, A. B cells responses and cytokine production are regulated by their immune microenvironment. Cytokine 74, 318–326 (2015).Article

Vazquez，M.I.，Catalan Dibene，J。＆Zlotnik，A。B细胞反应和细胞因子产生受其免疫微环境的调节。细胞因子74318-326（2015）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

He, B. et al. Comparative global B cell receptor repertoire difference induced by SARS-CoV-2 infection or vaccination via single-cell V(D)J sequencing. Emerg. Microbes Infect. 11, 2007–2020 (2022).Article

He，B。等人。通过单细胞V（D）J测序，由SARS-CoV-2感染或疫苗接种诱导的比较性全球B细胞受体库差异。紧急微生物感染。2007年11月至2020年（2022年）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Khoury, D. S. et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat. Med. 27, 1205–1211 (2021).Article

Khoury，D.S.等人。中和抗体水平高度预测免疫保护免受症状性SARS-CoV-2感染。《自然医学》271205-1211（2021）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Yinda, C. K. et al. K18-hACE2 mice develop respiratory disease resembling severe COVID-19. PLoS Pathog. 17, e1009195 (2021).Article

Yinda，C.K。等人，K18-hACE2小鼠发生类似于严重COVID-19的呼吸系统疾病。PLoS Pathog。17，e1009195（2021）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Milacic, M. et al. The reactome pathway knowledgebase 2024. Nucleic Acids Res 52, D672–d678 (2024).Article

Milacic，M.等人，《反应组途径知识库2024》。核酸研究52，D672–d678（2024）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Cao, Y. et al. Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies. Nature 602, 657–663 (2022).Article

Cao，Y。等人Omicron逃脱了大多数现有的SARS-CoV-2中和抗体。自然602657-663（2022）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Ai, J. et al. Antibody evasion of SARS-CoV-2 Omicron BA.1, BA.1.1, BA.2, and BA.3 sub-lineages. Cell Host Microbe 30, 1077–1083.e1074 (2022).Article

Ai，J。等人。SARS-CoV-2 Omicron BA.1，BA.1.1，BA.2和BA.3亚谱系的抗体逃避。细胞宿主微生物301077-1083.e1074（2022）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Iketani, S. et al. Antibody evasion properties of SARS-CoV-2 Omicron sublineages. Nature 604, 553–556 (2022).Article

Iketani，S。等人。SARS-CoV-2 Omicron亚系的抗体逃避特性。自然604553-556（2022）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Dejnirattisai, W. et al. SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses. Cell 185, 467–484.e415 (2022).Article

Dejnirattisai，W。等人。SARS-CoV-2 Omicron-B.1.1.529导致广泛逃避中和抗体反应。细胞185467-484.e415（2022）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Faraone, J. N. et al. Immune evasion and membrane fusion of SARS-CoV-2 XBB subvariants EG.5.1 and XBB.2.3. Emerg. Microbes Infect. 12, 2270069 (2023).Article

。紧急微生物感染。12227069（2023）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Yang, S. et al. Antigenicity and infectivity characterisation of SARS-CoV-2 BA.2.86. Lancet Infect. Dis. 23, e457–e459 (2023).Article

。柳叶刀感染。Dis。23，e457–e459（2023）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Gilbert, P. B. et al. Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial. Science 375, 43–50 (2022).Article

Gilbert，P.B。等人。mRNA-1273 COVID-19疫苗效力临床试验的免疫相关性分析。科学375,43-50（2022）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Bergwerk, M. et al. Covid-19 breakthrough infections in vaccinated health care workers. N. Engl. J. Med. 385, 1474–1484 (2021).Article

Bergwerk，M。等人。接种疫苗的医护人员中的新型冠状病毒突破性感染。N、 英语。J、 医学3851474-1484（2021）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Chandler, T. L., Yang, A., Otero, C. E., Permar, S. R. & Caddy, S. L. Protective mechanisms of nonneutralizing antiviral antibodies. PLoS pathog. 19, e1011670 (2023).Article

Chandler，T.L.，Yang，A.，Otero，C.E.，Permar，S.R。＆Caddy，S.L。非中和抗病毒抗体的保护机制。PLoS pathog。19，e1011670（2023）。文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Cao, Y. et al. BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection. Nature 608, 593–602 (2022).Article

。自然608593-602（2022）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Zhao, Y. et al. Vaccination with S, an antigen guided by SARS-CoV-2 S protein evolution, protects against challenge with viral variants in mice. Sci. Transl. Med. 15, eabo3332 (2023).Article

Zhao，Y。等人。用S（一种由SARS-CoV-2 S蛋白进化引导的抗原）接种疫苗，可以防止小鼠受到病毒变异的攻击。科学。翻译。医学杂志15，eabo3332（2023）。文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Download referencesAcknowledgementsThis study was supported by the Key Project of applied basic research in Yunnan Province (202401AS070049), CAMS Innovation Fund for Medical Sciences (2021-I2M-1-038, 2022-I2M-CoV19-002), National Key R&D Program of China (2021YFC230170402), Yunnan Key R&D Project (202103AQ100001).

下载参考文献致谢本研究得到了云南省应用基础研究重点项目（202401AS070049），CAMS医学科学创新基金（2021-I2M-1-0382022-I2M-CoV19-002），国家重点研发计划（2021YFC230170402），云南省重点研发项目（202103AQ100001）的支持。

We appreciate the services of all staff at the National Kunming High-level Biosafety Primate Research Center.Author informationAuthor notesThese authors contributed equally: Ran An, Hao Yang, Cong Tang, Qianqian Li, Qing Huang.Authors and AffiliationsInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, ChinaRan An, Hao Yang, Cong Tang, Qianqian Li, Qing Huang, Haixuan Wang, Junbin Wang, Yanan Zhou, Yun Yang, Hongyu Chen, Wenhai Yu, Bai Li, Daoju Wu, Yong Zhang, Fangyu Luo, Wenqi Quan, Jingwen Xu, Dongdong Lin, Xiaoming Liang, Yuhuan Yan, Longhai Yuan, Xuena Du, Yuxia Yuan, Yanwen Li, Qiangming Sun, Youchun Wang & Shuaiyao LuKey Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education, Beijing, ChinaQianqian Li, Qiangming Sun, Youchun Wang & Shuaiyao LuState Key Laboratory of Respiratory Health and Multimorbidity, Beijing, ChinaQianqian Li, Qiangming Sun, Youchun Wang & Shuaiyao LuYunnan Provincial Key Laboratory of Vector-borne Diseases Control and Research, Kunming, ChinaQiangming Sun & Shuaiyao LuAuthorsRan AnView author publicationsYou can also search for this author in.

我们感谢国家昆明高级生物安全灵长类动物研究中心全体工作人员的服务。作者信息作者注意到这些作者做出了同样的贡献：冉安，郝阳，丛唐，李千千，黄青。作者和所属单位中国医学科学院和北京协和医学院医学生物学研究所，昆明，中国安，杨浩，丛唐，李千千，黄青，王海轩，王俊斌，周亚楠，杨云，陈宏宇，余文海，白丽，吴道菊，张勇，罗方宇，文启全，徐敬文，林东东，梁晓明，严玉环，龙海源，杜雪娜，袁玉霞，李燕文，孙强明，王友春，帅耀鲁基病原体感染预防与控制实验室（北京协和医学院），教育部，北京，中国李倩，孙强明，王友春和帅瑶，中国北京，呼吸健康与多发病重点实验室李倩，孙强明，王友春和帅瑶，云南省媒介传播疾病控制与研究重点实验室，昆明，孙强明和帅瑶，作者RAN AnView作者出版物您也可以在中搜索作者。

PubMed Google ScholarHao YangView author publicationsYou can also search for this author in

PubMed Google ScholarHao YangView作者出版物您也可以在

PubMed Google ScholarCong TangView author publicationsYou can also search for this author in

PubMed Google ScholarCong TangView作者出版物您也可以在

PubMed Google ScholarQianqian LiView author publicationsYou can also search for this author in

PubMed Google ScholarQianqian LiView作者出版物您也可以在

PubMed Google ScholarQing HuangView author publicationsYou can also search for this author in

PubMed Google ScholarQing HuangView作者出版物您也可以在

PubMed Google ScholarHaixuan WangView author publicationsYou can also search for this author in

PubMed Google ScholarHaixuan WangView作者出版物您也可以在

PubMed Google ScholarJunbin WangView author publicationsYou can also search for this author in

PubMed谷歌学者Junbin WangView作者出版物您也可以在

PubMed Google ScholarYanan ZhouView author publicationsYou can also search for this author in

PubMed Google ScholarYanan ZhouView作者出版物您也可以在

PubMed Google ScholarYun YangView author publicationsYou can also search for this author in

PubMed Google ScholarYun YangView作者出版物您也可以在

PubMed Google ScholarHongyu ChenView author publicationsYou can also search for this author in

PubMed谷歌学者陈宏宇查看作者出版物您也可以在

PubMed Google ScholarWenhai YuView author publicationsYou can also search for this author in

PubMed Google ScholarWenhai YuView作者出版物您也可以在

PubMed Google ScholarBai LiView author publicationsYou can also search for this author in

PubMed Google ScholarBai LiView作者出版物您也可以在

PubMed Google ScholarDaoju WuView author publicationsYou can also search for this author in

PubMed谷歌学者Aoju WuView作者出版物您也可以在

PubMed Google ScholarYong ZhangView author publicationsYou can also search for this author in

PubMed Google ScholarYong ZhangView作者出版物您也可以在

PubMed Google ScholarFangyu LuoView author publicationsYou can also search for this author in

PubMed谷歌学者Fangyu LuoView作者出版物您也可以在

PubMed Google ScholarWenqi QuanView author publicationsYou can also search for this author in

PubMed Google ScholarWenqi QuanView作者出版物您也可以在

PubMed Google ScholarJingwen XuView author publicationsYou can also search for this author in

PubMed Google ScholarJingwen XuView作者出版物您也可以在

PubMed Google ScholarDongdong LinView author publicationsYou can also search for this author in

PubMed Google ScholarDongdong LinView作者出版物您也可以在

PubMed Google ScholarXiaoming LiangView author publicationsYou can also search for this author in

PubMed谷歌学者梁晓明查看作者出版物您也可以在

PubMed Google ScholarYuhuan YanView author publicationsYou can also search for this author in

PubMed Google ScholarYuhuan YanView作者出版物您也可以在

PubMed Google ScholarLonghai YuanView author publicationsYou can also search for this author in

PubMed Google ScholarLonghai YuanView作者出版物您也可以在

PubMed Google ScholarXuena DuView author publicationsYou can also search for this author in

PubMed Google ScholarXuena DuView作者出版物您也可以在

PubMed Google ScholarYuxia YuanView author publicationsYou can also search for this author in

PubMed Google ScholarYuxia YuanView作者出版物您也可以在

PubMed Google ScholarYanwen LiView author publicationsYou can also search for this author in

PubMed Google ScholarYanwen LiView作者出版物您也可以在

PubMed Google ScholarQiangming SunView author publicationsYou can also search for this author in

PubMed Google ScholarQiangming SunView作者出版物您也可以在

PubMed Google ScholarYouchun WangView author publicationsYou can also search for this author in

PubMed Google ScholarYouchun WangView作者出版物您也可以在

PubMed Google ScholarShuaiyao LuView author publicationsYou can also search for this author in

PubMed Google ScholarShuaiao LuView作者出版物您也可以在

PubMed Google ScholarContributionsThe experimental design was done by Shuaiyao Lu, Youchun Wang, Qiangming Sun, Ran An, and Hao Yang. Vaccine design and obtaining were done by Shuaiyao Lu, Hao Yang, and Ran An. Animal immunization and sampling were performed by Cong Tang, Ran An, and Junbin Wang.

PubMed谷歌学术贡献实验设计由Lu Shuaiyao，Wang Youchun，Xiangming Sun，Ran An和Hao Yang完成。疫苗设计和获得由Lu Shuaiyao，Hao Yang和Ran An完成。动物免疫和取样由Cong Tang，Ran An和Junbin Wang进行。

Virus neutralization experiment was completed by Ran An, Qianqian Li, Hao Yang, and Yanan Zhou. ELISPOTS experiment was completed by Ran An, Yuhuan Yan, and Longhai Yuan. Multifactor detection experiment was completed by Yun Yang and Ran Aan. Bioinformatics analysis was completed by Hongyu Chen and Ran An.

病毒中和实验由冉安，李倩倩，杨浩和周亚南完成。ELISPOTS实验由冉安，严玉环和袁龙海完成。多因素检测实验由Yun Yang和Ran Aan完成。生物信息学分析由陈宏宇完成，并运行了一个。

Protein structure and protein-protein interaction prediction were completed by Longhai Yuan. Challenge assay was completed by Qing Huang, Haixuan Wang, Yun Yang, Wenhai Yu, Bai Li, Daoju Wu, Yong Zhang, Fangyu Luo, Wenqi Quan, Jingwen Xu, Dongdong Lin, Xiaoming Liang, Yuhuan Yan, Longhai Yuan, Xuena Du, Yuxia Yuan, and Yanwen Li.

蛋白质结构和蛋白质-蛋白质相互作用预测由龙海苑完成。挑战测定由黄青、王海轩、杨云、余文海、白丽、吴道菊、张勇、罗方宇、文奇泉、徐静文、林东东、梁晓明、严玉环、袁龙海、杜雪娜、袁玉霞和李彦文完成。

Ran An, Hao Yang, Cong Tang, Qianqian Li, Qing Huang, and Haixuan Wang wrote the manuscript. Shuaiyao Lu, Youchun Wang, and Qiangming Sun reviewed the manuscript. All authors have read and approved the article.Corresponding authorsCorrespondence to.

冉安，郝阳，丛唐，李倩倩，黄青和王海轩撰写了手稿。陆帅耀，王友春和孙强明审阅了手稿。所有作者都阅读并批准了这篇文章。通讯作者通讯。

Qiangming Sun, Youchun Wang or Shuaiyao Lu.Ethics declarations

孙强明、王友春或路帅耀。道德宣言

Competing interests

The authors declare no competing interests.

作者声明没有利益冲突。

Supplementary informationSupplementary informationRights and permissions

补充信息补充信息权限

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

开放获取本文是根据知识共享署名4.0国际许可证授权的，该许可证允许以任何媒体或格式使用，共享，改编，分发和复制，只要您对原始作者和来源给予适当的信任，提供知识共享许可证的链接，并指出是否进行了更改。

The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

本文中的图像或其他第三方材料包含在文章的知识共享许可中，除非在材料的信用额度中另有说明。如果材料未包含在文章的知识共享许可中，并且您的预期用途不受法律法规的许可或超出许可用途，则您需要直接获得版权所有者的许可。

To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/..

要查看此许可证的副本，请访问http://creativecommons.org/licenses/by/4.0/..

Reprints and permissionsAbout this articleCite this articleAn, R., Yang, H., Tang, C. et al. A protein vaccine of RBD integrated with immune evasion mutation shows broad protection against SARS-CoV-2.

转载和许可本文引用本文An，R.，Yang，H.，Tang，C。等人。结合免疫逃避突变的RBD蛋白疫苗显示出对SARS-CoV-2的广泛保护作用。

Sig Transduct Target Ther 9, 301 (2024). https://doi.org/10.1038/s41392-024-02007-8Download citationReceived: 21 March 2024Revised: 24 September 2024Accepted: 07 October 2024Published: 06 November 2024DOI: https://doi.org/10.1038/s41392-024-02007-8Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

Sig Transduct Target Ther 9301（2024）。https://doi.org/10.1038/s41392-024-02007-8Download引文接收日期：2024年3月21日修订日期：2024年9月24日接受日期：2024年10月7日发布日期：2024年11月6日OI：https://doi.org/10.1038/s41392-024-02007-8Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

Provided by the Springer Nature SharedIt content-sharing initiative

由Springer Nature SharedIt内容共享计划提供