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A spike-trimer protein-based tetravalent COVID-19 vaccine elicits enhanced breadth of neutralization against SARS-CoV-2 omicron subvariants and other variants

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Science China(Life Sciences) 2023年第8期66卷 1818-1830页

作者： Rui Wang Hongpeng Huang Chulin Yu Chunyun Sun Juan Ma Desheng Kong Yalong Lin Dandan Zhao Shaozheng Zhou Jianbo Lu Sai Cao Yanjing Zhang Chunxia Luo Xuefeng Li Yang Wang Liangzhi Xie Beijing Protein and Antibody R&D Engineering Center Sinocelltech Ltd.Beijing 100176China Cell Culture Engineering Center Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China

Multivalent vaccines combining crucial mutations from phylogenetically divergent variants could be an effective approach to defend against existing and future SARS-Co V-2 *** this study,we developed a tetravalent COVID-19 vaccine SCTV01E,based on the trimeric Spike protein of SARS-Co V-2 variants Alpha,Beta,Delta,and omicron BA.1,with a squalenebased oil-in-water adjuvant *** the immunogenicity studies in na?ve BALB/c and C57BL/6J mice,SCTV01E exhibited the most favorable immunogenic characteristics to induce balanced and broad-spectrum neutralizing potencies against pre-omicron variants(D614G,Alpha,Beta,and Delta)and newly emerging omicron subvariants(BA.1,BA.1.1,BA.2,BA.3,and BA.4/5).Booster studies in C57BL/6J mice previously immunized with D614G monovalent vaccine demonstrated superior neutralizing capacities of SCTV01E against omicron subvariants,compared with the D614G booster ***,SCTV01E vaccination elicited na?ve and central memory T cell responses to SARS-Co V-2 ancestral strain and omicron spike ***,our comprehensive immunogenicity evaluation results indicate that SCTV01E could become an important COVID-19 vaccine platform to combat surging infections caused by the highly immune evasive BA.4/5 ***01E is currently being studied in a head-to-head immunogenicity comparison phase 3 clinical study with inactivated and m RNA vaccines(NCT05323461).

关键词： tetravalent SARS-CoV-2 vaccine omicron subvariants broad neutralization

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Dynamic Humoral Immune Response to Primary and Booster Inactivated SARS-CoV-2 Vaccination in Patients with Cirrhosis

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Journal of Clinical and Translational Hepatology 2023年第7期11卷 1476-1484页

作者： Qian Zhu Lu Wang Xiaoxiao Hu Yingzhi Zhang Tianquan Huang Taiyu He Zhiwei Chen Gaoli Zhang Mingli Peng Min Chen Dachuan Cai Xiaofeng Shi Hong Ren Department of Infectious Diseases Key Laboratory of Molecular Biology for Infectious Diseases(Ministry of Education)Institute for Viral HepatitisThe Second Affiliated HospitalChongqing Medical UniversityChongqingChina

Background and Aims:Our aim was to determine the immune efficacy of a severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)booster vaccination in cirrhotic patients who had received the primary ***:We performed a longitudinal assessment in 48 patients with cirrhosis,57 patients with chronic hepatitis B(CHB)and 68 healthy controls(HCs)to continuously track the dynamics of SARS-CoV-2 specific antibodies and memory B cells after receiving the primary series and booster dose at different times.A pseudovirus neutralization assay was used to determine neutralization against omicron subvariants BA.2.12.1,BA.4 and BA.5 from serum samples collected from three ***:Serum anti-receptor-binding domain(RBD)immunoglobulin(Ig)G and neutralizing antibody(NAb)levels in cirrhotic patients were elevated within 15–45 days after completing the primary series before rapidly declining and reaching a valley at around 165–195 *** receiving the booster dose,both antibody levels were significantly increased to levels comparable to patients with CHB and *** analysis showed that booster vaccination induced weaker antibody responses in patients with decompensated cirrhosis than in those with compensated *** SARS-CoV-2 memory B-cell response in cirrhotic patients was durable during follow-up regardless of the hepatic fibrocirrhosis ***,compared with the primary series,the booster dose did not result in an evident improvement of neutralization activity against the omicron subvariants BA.2.12.1 and BA.4,and was followed by a significant decrease in the titer against ***:A booster dose elicited a robust and durable humoral response to the wild-type strain in cirrhotic patients but not the omicron *** vaccination of inactivated SARS-CoV-2 vaccine may not benefit cirrhotic patients in neutralization against newly circulating strains.

关键词： SARS-CoV-2 omicron subvariants Cirrhosis Booster dose Humoral response

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Quantification and Differentiation of SARS-CoV‑2 Variants in Wastewater for Surveillance

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Environment & Health 2023年第3期1卷 203-213页

作者： Teresa Kumblathan Yanming Liu Xiaoli Pang Steve E.Hrudey XChris Le Xing-Fang Li Division of Analytical and Environmental Toxicology Department of Laboratory Medicine and PathologyFaculty of Medicine and DentistryUniversity of AlbertaEdmontonAlbertaCanada T6G 2G3 Division of Diagnostic and Applied Microbiology Department of Laboratory Medicine and PathologyFaculty of Medicine and DentistryUniversity of AlbertaEdmontonAlbertaCanada T6G 2B7 Public Health Laboratory Alberta Precision LaboratoriesEdmontonAlbertaCanada T6G 2J2

Wastewater surveillance plays an important role in the monitoring of infections of SARS-CoV-2 at the community *** report here the determination of SARS-CoV-2 and differentiation of its variants of concern in 294 wastewater samples collected from two major Canadian cities from May 2021 to March *** overall method of analysis involved extraction of the virus and viral components using electronegative membranes,in situ stabilization and concentration of the viral RNA onto magnetic beads,and direct analysis of the viral RNA on the magnetic *** reverse transcription quantitative polymerase chain reaction(RT-qPCR)assays,targeting specific and naturally selected mutations in SARS-CoV-2,enabled detection and differentiation of the Alpha,Beta,Gamma,Delta,and omicron *** omicron triplex RT-qPCR assay targeting three mutations,HV 69−70 deletion,K417N,and L452R,was able to detect and differentiate the omicron BA.1/BA.3,BA.2/XBB,and BA.4/*** assay had efficiencies of 90−104%for all three mutation targets and a limit of detection of 28 RNA copies per *** of 294 wastewater samples collected over a two-year span showed the concentrations and trends of Alpha,Beta,Gamma,Delta,and omicron variants as they emerge in two major Canadian cities participating in the wastewater surveillance *** trends of specific variants were consistent with clinical reports for the same *** the beginning of each wave,the corresponding variants were detectable in *** example,RNA concentrations of the BA.2 variant were as high as 10^(4)copies per 100 mL of wastewater collected in January 2022,when approximately only 50−60 clinical cases of BA.2 infection were reported in *** results show that the strategy and highly sensitive assays for the variants of concern in wastewater are potentially useful for the detection of newly emerging SARS-CoV-2 variants and other viruses for future community biomonitoring.

关键词： COVID-19 SARS-CoV-2 variants of concern omicron subvariants multiplex RT-qPCR wastewater surveillance

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Original Antigenic Sin on Antibody Response in SARS-CoV-2 Infection

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Infectious Diseases & Immunity 2024年第3期4卷 132-137页

作者： Miao Wang Huimin Guo Bin Ju Zheng Zhang Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People’s HospitalThe Second Affiliated HospitalSchool of MedicineSouthern University of Science and TechnologyShenzhen 518112Guangdong ProvinceChina Guangdong Key Laboratory for Anti-infection Drug Quality Evaluation Shenzhen 518112Guangdong ProvinceChina Shenzhen Research Center for Communicable Disease Diagnosis and Treatment Chinese Academy of Medical SciencesShenzhen 518112Guangdong ProvinceChina

Infection and vaccination can provide protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the emergence of SARS-CoV-2 variants has persisted, leading to breakthrough infections. Owing to the original antigenic sin (OAS), variant breakthrough infection or vaccination potentially induces a stronger antibody response against the ancestral strain than to subsequent variants, as in the case of influenza. Thus, overcoming OAS is important for the development of future vaccine designs. This review summarizes the recent findings on OAS in the antibody response to SARS-CoV-2 and its variants, with an emphasis on future vaccine designs.

关键词： SARS-CoV-2 Original antigenic sin Antibody response omicron subvariants Vaccine design

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