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Intranasal adenovirus-vectored Omicron vaccine induced nasal immunoglobulin A has superior neutralizing potency than serum antibodies

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3507-3518页

作者： Si Chen Zhengyuan Zhang Qian Wang Qi Yang Li Yin Lishan Ning Zhilong Chen Jielin Tang Weiqi Deng Ping He Hengchun Li Linjing Shi yjun Deng Zijian Liu Hemeng Bu Yaohui Zhu Wenming Liu linbing qu Ligiang Feng Xiaoli Xiong Baoqing Sun Nanshan Zhong Feng Li ingchao Li Xinwen Chen Ling Chen Guangzhou Institute of Infectious Disease Guangzhou Eighth People's HospitalGuangzhou Medical UniversityGuangzhouChina Guangzhou National Laboratory GuangzhouChina State Key Laboratory of Respiratory Disease Center for Cell Lineage ResearchGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouChina University of Chinese Academy of Sciences BeijingChina State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Xiamen United Institute of Respiratory Health XiamenChina

The upper respiratory tract is the initial site of SARS-CoV-2 *** spike-specific secretory immunoglobulin A(slgA)correlates with protection against Omicron breakthrough *** report that intranasal vaccination using human adenovirus serotype 5(Ad5)vectored Omicron spike in people who previously vaccinated with ancestral vaccine could induce robust neutralizing slgA in the nasal *** slgA was predominantly present in dimeric and multimeric forms and accounted for nearly 40%of total proteins in nasal mucosal lining fluids(NMLFs).A low-level IgG could also be detected in NMLFs but not IgM,IgD,and *** a complete nasal wash,slgA in the nasal passage could be replenished rapidly within a few hours.A comparison of purified paired serum IgA,serum IgG,and nasal slgA from the same individuals showed that slgA was up to 3-logs more potent than serum antibodies in binding to spikes and in neutralizing Omicron *** IgG and IgA failed to neutralize XBB and BA.2.86,while nasal slgA retained potent neutralization against these newly emerged *** analysis showed that slgA Was more effective than IgG or IgA in blocking spike-mediated cell-to-cell transmission and protecting hACE2 mice from XBB *** a slgA monoclonal antibody as a reference,we estimated that the total nasal slgA contains about 2.6-3.9%spikespecific slgA in NMLFs collected approximately one month after intranasal *** study provided insights for developing intranasal vaccines that can induce slgA to build an effective and mutation-resistant first-line immune barrier against constantly emerging variants.

关键词： nasal antibodies neutral

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Intranasal booster using an Omicron vaccine confers broad mucosal and systemic immunity against SARS-CoV-2 variants

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2345-2353页

作者： Qian Wang Chenchen Yang Li Yin Jing Sun Wei Wang Hengchun Li Zhengyuan Zhang Si Chen Bo Liu Zijian Liu Linjing Shi Xiaolin Liu Suhua Guan Chunhua Wang linbing qu Ying Feng Xuefeng Niu Liqiang Feng Jincun Zhao Pingchao Li Ling Chen Nanshan Zhong State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Guangzhou nBiomed Ltd. GuangzhouChina Guangzhou Laboratory&Bioland Laboratory GuangzhouChina Guangdong Laboratory of Computational Biomedicine Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouChina University of Chinese Academy of Sciences BeijingChina

The highly contagious SARS-CoV-2 Omicron subvariants severely attenuated the effectiveness of currently licensed SARS-CoV-2 vaccines based on ancestral strains administered via intramuscular *** this study,we generated a recombinant,replication-incompetent human adenovirus type 5,Ad5-S-Omicron,that expresses Omicron BA.1 ***,but not intramuscular vaccination,elicited spike-specific respiratory mucosal IgA and residential T cell immune responses,in addition to systemic neutralizing antibodies and T cell immune responses against most Omicron *** tested intranasal Ad5-S-Omicron as a heterologous booster in mice that previously received intramuscular injection of inactivated ancestral *** addition to inducing serum broadly neutralizing antibodies,there was a significant induction of respiratory mucosal IgA and neutralizing activities against Omicron subvariants BA.1,BA.2,BA.5,BA.2.75,BF.7 as well as pre-Omicron strains Wildtype,Beta,and *** and mucosal neutralizing activities against recently emerged XBB,BQ.1,and BQ.1.1 could also be detected but were much *** lavage fluids from intranasal vaccination contained multimeric IgA that can bind to at least 10 spike proteins,including Omicron subvariants and pre-Omicron strains,and possessed broadly neutralizing *** vaccination using Ad5-S-Omicron or instillation of intranasal vaccinee’s nasal lavage fluids in mouse nostrils protected mice against Omicron *** together,intranasal Ad5-S-Omicron booster on the basis of ancestral vaccines can establish effective mucosal and systemic immunity against Omicron subvariants and multiple SARS-CoV-2 *** candidate vaccine warrants further development as a safe,effective,and user-friendly infection and transmission-blocking vaccine.

关键词： nasal immunity mucosal

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饥饿状态下HNF4α对MTP的表达调控

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中国科学技术大学学报 2010年第7期40卷 673-678页

作者：瞿林兵谭文娟管敏黄志伟陈凌中国科学院广州生物医药与健康研究院广东广州510530 中国科学技术大学生命科学学院安徽合肥230027

肝细胞核因子4α(HNF4α)是肝脏中一种重要的转录因子,其参与多个代谢途径的调控.微粒体甘油三酯转运蛋白(MTP)是极低密度脂蛋白装配和分泌过程的限速酶.C57BL/6J小鼠中研究发现,饥饿可以诱导肝细胞MTP基因的表达.在HepG2细胞中进一步... 详细信息

肝细胞核因子4α(HNF4α)是肝脏中一种重要的转录因子,其参与多个代谢途径的调控.微粒体甘油三酯转运蛋白(MTP)是极低密度脂蛋白装配和分泌过程的限速酶.C57BL/6J小鼠中研究发现,饥饿可以诱导肝细胞MTP基因的表达.在HepG2细胞中进一步证实饥饿可以诱导MTP表达,同时HNF4α表达也显著上升.实验证实MTP是HNF4α的靶基因之一,用腺病毒介导的HNF4α过表达和HNF4α的激动剂均显著提高MTP的表达;HNF4α特异性siRNA抑制HNF4α的表达,MTP的mRNA和蛋白水平相应下调.结果证明,在饥饿状态下可以诱导MTP和HNF4α的表达,MTP的表达量上升是受到HNF4α的转录调控.

关键词：肝细胞核因子4α 微粒体甘油三酯转运蛋白饥饿

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Correction To:Intranasal booster using an Omicron vaccine confers broad mucosal and systemic immunity against SARSCoV-2 variants

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Signal Transduction and Targeted Therapy 2023年第6期8卷 3184-3184页

作者： Qian Wang Chenchen Yang Li Yin Jing Sun Wei Wang Hengchun Li Zhengyuan Zhang Si Chen Bo Liu Zijian Liu Linjing Shi Xiaolin Liu Suhua Guan Chunhua Wang linbing qu Ying Feng Xuefeng Niu Liqiang Feng Jincun Zhao Pingchao Li Ling Chen Nanshan Zhong The First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory Health Guangzhou China (GRID:grid.470124.4) Guangzhou nBiomed Ltd. Guangzhou China (GRID:grid.470124.4) Guangzhou Laboratory & Bioland Laboratory Guangzhou China (GRID:grid.508040.9) (ISNI:0000 0004 9415 435X) Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangdong Laboratory of Computational Biomedicine Guangzhou China (GRID:grid.428926.3) (ISNI:0000 0004 1798 2725) University of Chinese Academy of Sciences Beijing China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419) Guangzhou Laboratory & Bioland Laboratory Guangzhou China (GRID:grid.508040.9) (ISNI:0000 0004 9415 435X) Guangzhou nBiomed Ltd. Guangzhou China (GRID:grid.508040.9) Guangzhou Laboratory & Bioland Laboratory Guangzhou China (GRID:grid.508040.9) (ISNI:0000 0004 9415 435X) Guangzhou nBiomed Ltd. Guangzhou China (GRID:grid.410726.6) Guangzhou Laboratory & Bioland Laboratory Guangzhou China (GRID:grid.508040.9) (ISNI:0000 0004 9415 435X) Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangdong Laboratory of Computational Biomedicine Guangzhou China (GRID:grid.428926.3) (ISNI:0000 0004 1798 2725) The First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory Health Guangzhou China (GRID:grid.470124.4) Guangzhou Laboratory & Bioland Laboratory Guangzhou China (GRID:grid.508040.9) (ISNI:0000 0004 9415 435X) The First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory Health Guangzhou China (GRID:grid.470124.4) Guangzhou Laboratory & Bioland Laboratory Guangzhou China (GRID:grid.508040.9) (ISNI:0000 0004 9415 435X) Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangdong Laboratory of Computational Biomedicine Guangzhou

Correction to:Signal Transduction and Targeted Therapy https://***/10.1038/s41392-023-01423-6,published online 17 April 2023 After online publication of the article^(1),the authors noticed two inadvertent mistakes occ... 详细信息

关键词： immunity mistake noticed

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