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  1. Article ; Online: Three-dose vaccination-induced immune responses protect against SARS-CoV-2 Omicron BA.2

    Runhong Zhou / Na Liu / Xin Li / Qiaoli Peng / Cheuk-Kwan Yiu / Haode Huang / Dawei Yang / Zhenglong Du / Hau-Yee Kwok / Ka-Kit Au / Jian-Piao Cai / Ivan Fan-Ngai Hung / Kelvin Kai-Wang To / Xiaoning Xu / Kwok-Yung Yuen / Zhiwei Chen

    The Lancet Regional Health. Western Pacific, Vol 32, Iss , Pp 100660- (2023)

    a population-based study in Hong KongResearch in context

    2023  

    Abstract: Summary: Background: The ongoing outbreak of SARS-CoV-2 Omicron BA.2 infections in Hong Kong, the model city of universal masking of the world, has resulted in a major public health crisis. Although the third vaccination resulted in strong boosting of ... ...

    Abstract Summary: Background: The ongoing outbreak of SARS-CoV-2 Omicron BA.2 infections in Hong Kong, the model city of universal masking of the world, has resulted in a major public health crisis. Although the third vaccination resulted in strong boosting of neutralization antibody, vaccine efficacy and correlate of immune protection against the major circulating Omicron BA.2 remain to be investigated. Methods: We investigated the vaccine efficacy against the Omicron BA.2 breakthrough infection among 470 public servants who had received different SARS-CoV-2 vaccine regimens including two-dose BNT162b2 (2 × BNT, n = 169), three-dose BNT162b2 (3 × BNT, n = 168), two-dose CoronaVac (2 × CorV, n = 34), three-dose CoronaVac (3 × CorV, n = 67) and third-dose BNT162b2 following 2 × CorV (2 × CorV+1BNT, n = 32). Humoral and cellular immune responses after three-dose vaccination were further characterized and correlated with clinical characteristics of BA.2 infection. Findings: During the BA.2 outbreak, 27.7% vaccinees were infected. The timely third-dose vaccination provided significant protection with lower incidence rates of breakthrough infections (2 × BNT 46.2% vs 3 × BNT 13.1%, p < 0.0001; 2 × CorV 44.1% vs 3 × CorV 19.4%, p = 0.003). Investigation of immune responses on blood samples derived from 90 subjects in three-dose vaccination cohorts collected before the BA.2 outbreak revealed that the third-dose vaccination activated spike (S)-specific memory B cells and Omicron cross-reactive T cell responses, which correlated with reduced frequencies of breakthrough infections and disease severity rather than with types of vaccines. Moreover, the frequency of S-specific activated memory B cells was significantly lower in infected vaccinees than uninfected vaccinees before vaccine-breakthrough infection whereas IFN-γ+ CD4 T cells were negatively associated with age and viral clearance time. Critically, BA.2 breakthrough infection boosted cross-reactive memory B cells with enhanced cross-neutralizing antibodies to Omicron ...
    Keywords SARS-CoV-2 ; COVID-19 ; Omicron ; BA.2 ; Breakthrough infection ; Neutralizing antibody ; Public aspects of medicine ; RA1-1270
    Subject code 630
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Waning immune responses against SARS-CoV-2 variants of concern among vaccinees in Hong Kong

    Qiaoli Peng / Runhong Zhou / Yuewen Wang / Meiqing Zhao / Na Liu / Shuang Li / Haode Huang / Dawei Yang / Ka-Kit Au / Hui Wang / Kwan Man / Kwok-Yung Yuen / Zhiwei Chen

    EBioMedicine, Vol 77, Iss , Pp 103904- (2022)

    2022  

    Abstract: Summary: Background: Nearly 4 billion doses of the BNT162b2-mRNA and CoronaVac-inactivated vaccines have been administrated globally, yet different vaccine-induced immunity against SARS-CoV-2 variants of concern (VOCs) remain incompletely investigated. ... ...

    Abstract Summary: Background: Nearly 4 billion doses of the BNT162b2-mRNA and CoronaVac-inactivated vaccines have been administrated globally, yet different vaccine-induced immunity against SARS-CoV-2 variants of concern (VOCs) remain incompletely investigated. Methods: We compare the immunogenicity and durability of these two vaccines among fully vaccinated Hong Kong people. Findings: Standard BNT162b2 and CoronaVac vaccinations were tolerated and induced neutralizing antibody (NAb) (100% and 85.7%) and spike-specific CD4 T cell responses (96.7% and 82.1%), respectively. The geometric mean NAb IC50 and median frequencies of reactive CD4 subsets were consistently lower among CoronaVac-vaccinees than BNT162b2-vaccinees. CoronaVac did not induce measurable levels of nucleocapsid protein-specific IFN-γ+ CD4+ T or IFN-γ+ CD8+ T cells compared with unvaccinated. Against VOCs, NAb response rates and geometric mean IC50 titers against B.1.617.2 (Delta) and B.1.1.529 (Omicron) were significantly lower for CoronaVac (50%, 23.2 and 7.1%, <20) than BNT162b2 (94.1%, 131 and 58.8%, 35.0), respectively. Three months after vaccinations, NAbs to VOCs dropped near to detection limit, along with waning memory T cell responses, mainly among CoronaVac-vaccinees. Interpretation: Our results indicate that vaccinees especially CoronaVac-vaccinees with significantly reduced NAbs may probably face higher risk to pandemic VOCs breakthrough infection. Funding: This study was supported by the Hong Kong Research Grants Council Collaborative Research Fund (C7156-20GF and C1134-20GF); the Wellcome Trust (P86433); the National Program on Key Research Project of China (Grant 2020YFC0860600, 2020YFA0707500 and 2020YFA0707504); Shenzhen Science and Technology Program (JSGG20200225151410198 and JCYJ20210324131610027); HKU Development Fund and LKS Faculty of Medicine Matching Fund to AIDS Institute; Hong Kong Innovation and Technology Fund, Innovation and Technology Commission and generous donation from the Friends of Hope Education Fund. Z.C.’s team was also partly supported by the Theme-Based Research Scheme (T11-706/18-N).
    Keywords SARS-CoV-2 ; mRNA vaccine ; Inactivated vaccine ; Cellular immune response ; Humoral immune response ; Medicine ; R ; Medicine (General) ; R5-920
    Subject code 570
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: An intranasal influenza virus-vectored vaccine prevents SARS-CoV-2 replication in respiratory tissues of mice and hamsters

    Shaofeng Deng / Ying Liu / Rachel Chun-Yee Tam / Pin Chen / Anna Jinxia Zhang / Bobo Wing-Yee Mok / Teng Long / Anja Kukic / Runhong Zhou / Haoran Xu / Wenjun Song / Jasper Fuk-Woo Chan / Kelvin Kai-Wang To / Zhiwei Chen / Kwok-Yung Yuen / Pui Wang / Honglin Chen

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 12

    Abstract: Abstract Current available vaccines for COVID-19 are effective in reducing severe diseases and deaths caused by SARS-CoV-2 infection but less optimal in preventing infection. Next-generation vaccines which are able to induce mucosal immunity in the upper ...

    Abstract Abstract Current available vaccines for COVID-19 are effective in reducing severe diseases and deaths caused by SARS-CoV-2 infection but less optimal in preventing infection. Next-generation vaccines which are able to induce mucosal immunity in the upper respiratory to prevent or reduce infections caused by highly transmissible variants of SARS-CoV-2 are urgently needed. We have developed an intranasal vaccine candidate based on a live attenuated influenza virus (LAIV) with a deleted NS1 gene that encodes cell surface expression of the receptor-binding-domain (RBD) of the SARS-CoV-2 spike protein, designated DelNS1-RBD4N-DAF. Immune responses and protection against virus challenge following intranasal administration of DelNS1-RBD4N-DAF vaccines were analyzed in mice and compared with intramuscular injection of the BioNTech BNT162b2 mRNA vaccine in hamsters. DelNS1-RBD4N-DAF LAIVs induced high levels of neutralizing antibodies against various SARS-CoV-2 variants in mice and hamsters and stimulated robust T cell responses in mice. Notably, vaccination with DelNS1-RBD4N-DAF LAIVs, but not BNT162b2 mRNA, prevented replication of SARS-CoV-2 variants, including Delta and Omicron BA.2, in the respiratory tissues of animals. The DelNS1-RBD4N-DAF LAIV system warrants further evaluation in humans for the control of SARS-CoV-2 transmission and, more significantly, for creating dual function vaccines against both influenza and COVID-19 for use in annual vaccination strategies.
    Keywords Science ; Q
    Subject code 570
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Characterization of an attenuated SARS-CoV-2 variant with a deletion at the S1/S2 junction of the spike protein

    Pui Wang / Siu-Ying Lau / Shaofeng Deng / Pin Chen / Bobo Wing-Yee Mok / Anna Jinxia Zhang / Andrew Chak-Yiu Lee / Kwok-Hung Chan / Rachel Chun-Yee Tam / Haoran Xu / Runhong Zhou / Wenjun Song / Li Liu / Kelvin Kai-Wang To / Jasper Fuk-Woo Chan / Zhiwei Chen / Kwok-Yung Yuen / Honglin Chen

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 10

    Abstract: The S1/S2 junction of the SARS-CoV-2 Spike protein is emerging as a key factor in virulence and pathogenesis. Here, the authors characterise an attenuated strain of SARS-CoV-2 with deletions in the critical S1/S2 junction and observe enhanced replication, ...

    Abstract The S1/S2 junction of the SARS-CoV-2 Spike protein is emerging as a key factor in virulence and pathogenesis. Here, the authors characterise an attenuated strain of SARS-CoV-2 with deletions in the critical S1/S2 junction and observe enhanced replication, generation of potent adaptive immunity but reduced immunopathology in a hamster model of infection.
    Keywords Science ; Q
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: A broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge

    Biao Zhou / Runhong Zhou / Bingjie Tang / Jasper Fuk-Woo Chan / Mengxiao Luo / Qiaoli Peng / Shuofeng Yuan / Hang Liu / Bobo Wing-Yee Mok / Bohao Chen / Pui Wang / Vincent Kwok-Man Poon / Hin Chu / Chris Chung-Sing Chan / Jessica Oi-Ling Tsang / Chris Chun-Yiu Chan / Ka-Kit Au / Hiu-On Man / Lu Lu /
    Kelvin Kai-Wang To / Honglin Chen / Kwok-Yung Yuen / Shangyu Dang / Zhiwei Chen

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 14

    Abstract: SARS-CoV-2 variants of concern such as the Omicron variant pose a challenge for vaccination and antibody immunotherapy. Here, Zhou et al. isolate a broadly neutralizing antibody (bNAb), named ZCB11, that protects Golden Syrian hamsters against Omicron. ... ...

    Abstract SARS-CoV-2 variants of concern such as the Omicron variant pose a challenge for vaccination and antibody immunotherapy. Here, Zhou et al. isolate a broadly neutralizing antibody (bNAb), named ZCB11, that protects Golden Syrian hamsters against Omicron. Applying CryoEM the authors show that ZCB11 heavy chain predominantly interacts with RBD in up confirmation, which interferes with ACE2 receptor binding.
    Keywords Science ; Q
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccineResearch in context

    Georgia Deliyannis / Nicholas A. Gherardin / Chinn Yi Wong / Samantha L. Grimley / James P. Cooney / Samuel J. Redmond / Paula Ellenberg / Kathryn C. Davidson / Francesca L. Mordant / Tim Smith / Marianne Gillard / Ester Lopez / Julie McAuley / Chee Wah Tan / Jing J. Wang / Weiguang Zeng / Mason Littlejohn / Runhong Zhou / Jasper Fuk-Woo Chan /
    Zhi-wei Chen / Airn E. Hartwig / Richard Bowen / Jason M. Mackenzie / Elizabeth Vincan / Joseph Torresi / Katherine Kedzierska / Colin W. Pouton / Tom P. Gordon / Lin-fa Wang / Stephen J. Kent / Adam K. Wheatley / Sharon R. Lewin / Kanta Subbarao / Amy W. Chung / Marc Pellegrini / Trent Munro / Terry Nolan / Steven Rockman / David C. Jackson / Damian F.J. Purcell / Dale I. Godfrey

    EBioMedicine, Vol 92, Iss , Pp 104574- (2023)

    2023  

    Abstract: Summary: Background: The SARS-CoV-2 global pandemic has fuelled the generation of vaccines at an unprecedented pace and scale. However, many challenges remain, including: the emergence of vaccine-resistant mutant viruses, vaccine stability during storage ...

    Abstract Summary: Background: The SARS-CoV-2 global pandemic has fuelled the generation of vaccines at an unprecedented pace and scale. However, many challenges remain, including: the emergence of vaccine-resistant mutant viruses, vaccine stability during storage and transport, waning vaccine-induced immunity, and concerns about infrequent adverse events associated with existing vaccines. Methods: We report on a protein subunit vaccine comprising the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 spike protein, dimerised with an immunoglobulin IgG1 Fc domain. These were tested in conjunction with three different adjuvants: a TLR2 agonist R4-Pam2Cys, an NKT cell agonist glycolipid α-Galactosylceramide, or MF59® squalene oil-in-water adjuvant, using mice, rats and hamsters. We also developed an RBD-human IgG1 Fc vaccine with an RBD sequence of the immuno-evasive beta variant (N501Y, E484K, K417N). These vaccines were also tested as a heterologous third dose booster in mice, following priming with whole spike vaccine. Findings: Each formulation of the RBD-Fc vaccines drove strong neutralising antibody (nAb) responses and provided durable and highly protective immunity against lower and upper airway infection in mouse models of COVID-19. The ‘beta variant’ RBD vaccine, combined with MF59® adjuvant, induced strong protection in mice against the beta strain as well as the ancestral strain. Furthermore, when used as a heterologous third dose booster, the RBD-Fc vaccines combined with MF59® increased titres of nAb against other variants including alpha, delta, delta+, gamma, lambda, mu, and omicron BA.1, BA.2 and BA.5. Interpretation: These results demonstrated that an RBD-Fc protein subunit/MF59® adjuvanted vaccine can induce high levels of broadly reactive nAbs, including when used as a booster following prior immunisation of mice with whole ancestral-strain spike vaccines. This vaccine platform offers a potential approach to augment some of the currently approved vaccines in the face of emerging variants of ...
    Keywords SARS-CoV-2 ; COVID-19 ; Vaccine ; Receptor-binding domain ; RBD ; Medicine ; R ; Medicine (General) ; R5-920
    Subject code 572
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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