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Article: An RNA-Scaffold Protein Subunit Vaccine for Nasal Immunization.

Lam, Joy-Yan / Wong, Wan-Man / Yuen, Chun-Kit / Ng, Yau-Yee / San, Chun-Hin / Yuen, Kwok-Yung / Kok, Kin-Hang

2023 Volume 11, Issue 10

Abstract: Developing recombinant proteins as nasal vaccines for inducing systemic and mucosal immunity against respiratory viruses is promising. However, additional adjuvants are required to overcome the low immunogenicity of protein antigens. Here, a self- ... ...

Abstract	Developing recombinant proteins as nasal vaccines for inducing systemic and mucosal immunity against respiratory viruses is promising. However, additional adjuvants are required to overcome the low immunogenicity of protein antigens. Here, a self-adjuvanted protein-RNA ribonucleoprotein vaccine was developed and found to be an effective nasal vaccine in mice and the SARS-CoV-2 infection model. The vaccine consisted of spike RBD (as an antigen), nucleoprotein (as an adaptor), and ssRNA (as an adjuvant and RNA scaffold). This combination robustly induced mucosal IgA, neutralizing antibodies and activated multifunctional T-cells, while also providing sterilizing immunity against live virus challenge. In addition, high-resolution scRNA-seq analysis highlighted airway-resident immune cells profile during prime-boost immunization. The vaccine also possesses modularity (antigen/adaptor/RNA scaffold) and can be made to target other viruses. This protein-RNA ribonucleoprotein vaccine is a novel and promising approach for developing safe and potent nasal vaccines to combat respiratory virus infections.
Language	English
Publishing date	2023-09-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines11101550
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Comparison of assistance preferences of older adults with different functional dependence levels on domestic tasks performed by robots.

Lee, Linda Yin-King / Yeung, Chun-Kit / Choi, Chun-Wa / Leung, Man-Nga / Lui, Shing-Yan / Tam, Wing-Yi / Tang, Ka-Yi / Wong, Chun-San / Wong, Yuen-Shan / Yau, Cheuk-Yi / Yeung, Tik-Ling / Lee, Joseph Kok-Long / Chui, Debby Lee-Kuen

BMC geriatrics

2024 Volume 24, Issue 1, Page(s) 58

Abstract: Background: Robots have the potential to assist older adults in their home-based daily living tasks. Previous studies indicated that older adults generally accept robot assistance. However, the preferences of older adults with different functional ... ...

Abstract	Background: Robots have the potential to assist older adults in their home-based daily living tasks. Previous studies indicated that older adults generally accept robot assistance. However, the preferences of older adults with different functional dependence levels are lacking. These older adults encounter varying levels of difficulty in daily living and may have distinct preferences for robot assistance. This study aimed to describe and compare the preferences for robot assistance on domestic tasks in older adults with different functional dependence levels. Methods: This cross-sectional descriptive study recruited a convenience sample of 385 older adults in Hong Kong. They were categorized as independent, partially dependent, and dependent using the Katz Index of Independence in Activities of Daily Living. Their preferences for robot assistance on a list of 48 domestic tasks under six categories were assessed through the Assistance Preference Checklist. Differences in preferences between the three groups were compared using one-way ANOVA test. Results: Findings revealed the differences and similarities in preferences between participants with different dependence levels. In most domestic tasks under the personal care category, dependent and partially dependent older adults reported a significantly lower preferences for human assistance or a higher preferences for robot assistance (p < 0.001), compared with the independent ones. The effect size varied from medium to large (eta squared = 0.07 to 0.52). However, participants, regardless of functional dependence levels, preferred human to assist in some domestic tasks under the health and leisure activities category and preferred robot to assist in most of the domestic tasks under the chores, information management, and manipulating objects category. Conclusions: Older adults with different levels of functional dependence exhibit different preferences for robotic assistance. To effectively use robots and assist older adults as they age, the specific preferences of older adults must be considered before designing and introducing robots in domestic care.
MeSH term(s)	Humans ; Aged ; Activities of Daily Living ; Functional Status ; Robotics ; Cross-Sectional Studies ; Self Care
Language	English
Publishing date	2024-01-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2059865-8
ISSN	1471-2318 ; 1471-2318
ISSN (online)	1471-2318
ISSN	1471-2318
DOI	10.1186/s12877-023-04567-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A nasal omicron vaccine booster elicits potent neutralizing antibody response against emerging SARS-CoV-2 variants.

Lam, Joy-Yan / Ng, Yau-Yee / Yuen, Chun-Kit / Wong, Wan-Man / Yuen, Kwok-Yung / Kok, Kin-Hang

Emerging microbes & infections

2022 Volume 11, Issue 1, Page(s) 964–967

Abstract: SARS-CoV-2 has caused the COVID-19 pandemic since early 2020. As of January 2022, the worldwide spreading of SARS-CoV-2 leads to approximately 0.35 billion of human infections and five millions of deaths. Current vaccination is one of the effective ways ... ...

Abstract	SARS-CoV-2 has caused the COVID-19 pandemic since early 2020. As of January 2022, the worldwide spreading of SARS-CoV-2 leads to approximately 0.35 billion of human infections and five millions of deaths. Current vaccination is one of the effective ways to control SARS-CoV-2 transmission and reduce the disease severity. However, the antibody level against the immunogen significantly drops several months after the standard two-dose vaccination, and hence a third or fourth dose booster (the same immunogen) has been suggested to boost the antibody response. Here, we described an ultra-effective nasal vaccine booster that potently induced the extraordinary high-level of neutralizing antibody in pre-vaccinated mice. The vaccine booster is composed of a recombinant receptor binding domain of SARS-CoV-2 spike (either wild-type or omicron) fused with a domain of SARS-CoV-2 nucleoprotein. In the absence of adjuvants, a single intranasal administration of the booster in pre-vaccinated mice significantly induced systemic and mucosal antibody responses as evidenced by the elevation of the cross-variant neutralizing antibody and induction of IgA in bronchoalveolar lavage respectively. Most importantly, the single dose nasal vaccine booster (omicron version) potently enhanced the neutralizing activity against authentic SARS-CoV-2 omicron virus infection. Taken together, the induction of respiratory mucosal immunity and the enhancement of cross-variant neutralizing activity by the nasal vaccine booster warrants further clinical trials in humans.
MeSH term(s)	Animals ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; Mice ; Pandemics ; SARS-CoV-2 ; Vaccines
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; Vaccines
Language	English
Publishing date	2022-03-11
Publishing country	United States
Document type	Letter
ZDB-ID	2681359-2
ISSN	2222-1751 ; 2222-1751
ISSN (online)	2222-1751
ISSN	2222-1751
DOI	10.1080/22221751.2022.2053365
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: An interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal models.

Yuen, Chun-Kit / Wong, Wan-Man / Mak, Long-Fung / Lam, Joy-Yan / Cheung, Lok-Yi / Cheung, Derek Tsz-Yin / Ng, Yau-Yee / Lee, Andrew Chak-Yiu / Zhong, Nanshan / Yuen, Kwok-Yung / Kok, Kin-Hang

Nature communications

2023 Volume 14, Issue 1, Page(s) 6762

Abstract: A pan-sarbecovirus or pan-betacoronavirus vaccine that can prevent current and potential future beta-coronavirus infections is important for fighting possible future pandemics. Here, we report a mucosal vaccine that cross-protects small animal models ... ...

Abstract	A pan-sarbecovirus or pan-betacoronavirus vaccine that can prevent current and potential future beta-coronavirus infections is important for fighting possible future pandemics. Here, we report a mucosal vaccine that cross-protects small animal models from sarbecoviruses including SARS-CoV-1, SARS-CoV-2 and its variants. The vaccine comprises a live-but-defective SARS-CoV-2 virus that is envelope deficient and has the orf8 segment replaced by interferon-beta, hence named Interferon Beta Integrated SARS-CoV-2 (IBIS) vaccine. Nasal vaccination with IBIS protected mice from lethal homotypic SARS-CoV-2 infection and hamsters from co-housing-mediated transmission of homotypic virus. Moreover, IBIS provided complete protection against heterotypic sarbecoviruses, including SARS-CoV-2 Delta and Omicron variants, and SARS-CoV-1 in both mice and hamsters. Besides inducing a strong lung CD8 + T cell response, IBIS specifically heightened the activation of mucosal virus-specific CD4 + T cells compared to the interferon-null vaccine. The direct production of interferon by IBIS also suppressed virus co-infection of SARS-CoV-2 in human cells, reducing the risk of genetic recombination when using as live vaccines. Altogether, IBIS is a next-generation pan-sarbecovirus vaccine and warrants further clinical investigations.
MeSH term(s)	Cricetinae ; Humans ; Animals ; Mice ; Interferons ; Severe acute respiratory syndrome-related coronavirus ; Interferon-beta ; SARS-CoV-2 ; Vaccines, Attenuated ; Models, Animal ; Antibodies, Neutralizing ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus
Chemical Substances	Interferons (9008-11-1) ; Interferon-beta (77238-31-4) ; Vaccines, Attenuated ; Antibodies, Neutralizing ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus
Language	English
Publishing date	2023-10-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-42349-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: An Unusual Case of Intramyocardial Dissecting Hematoma.

Yuen, Ho-Chuen / Shek, Joyce / Wong, Chun-Kit / Tsui, Ping-Tim / Mok, Ngai-Shing / Chan, Ngai-Yin / Lo, Ka-Yip

CASE (Philadelphia, Pa.)

2021 Volume 6, Issue 1, Page(s) 16–20

Language	English
Publishing date	2021-08-26
Publishing country	United States
Document type	Case Reports
ISSN	2468-6441
ISSN (online)	2468-6441
DOI	10.1016/j.case.2021.07.015
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Loss of orf3b in the circulating SARS-CoV-2 strains.

Lam, Joy-Yan / Yuen, Chun-Kit / Ip, Jonathan Daniel / Wong, Wan-Man / To, Kelvin Kai-Wang / Yuen, Kwok-Yung / Kok, Kin-Hang

Emerging microbes & infections

2021 Volume 9, Issue 1, Page(s) 2685–2696

Abstract: The newly emerged betacoronavirus, SARS-CoV-2, causes the COVID-19 pandemic since December 2019 with more than 35 million laboratory confirmed human infections and over one million deaths within nine months. The genome of SARS-CoV-2 continues to evolve ... ...

Abstract	The newly emerged betacoronavirus, SARS-CoV-2, causes the COVID-19 pandemic since December 2019 with more than 35 million laboratory confirmed human infections and over one million deaths within nine months. The genome of SARS-CoV-2 continues to evolve during the global transmission with the notable emergence of the spike D614G substitution that enhances infectivity. Some of these viral adaptations may alter not only the infectivity but also viral pathogenesis. Continuous phylogenomic analysis of circulating viral strains and functional investigation of new non-synonymous substitutions may help to understand the evolution of virus, its virulence and transmissibility. Here we describe a loss of an accessory protein orf3b (57 amino acids) in current circulating SARS-CoV-2 strains, contributing around 24% of more than 100,000 complete viral genomes analysed. The loss of 3b is caused by the presence of an early stop codon which is created by an orf3a Q57H substitution. There is an increasing trend in the loss of orf3b which has reached 32% in May 2020. Geographically, loss of 3b is more prevalent in certain countries including Colombia (46%), USA (48%), South Korea (51%), France (66%), Saudi Arabia (72%), Finland (76%) and Egypt (77%). Interestingly, the loss of 3b coincides with the emergence of spike D614G substitution. In addition, we found that truncated orf3b has lost the interferon antagonism compared to the full-length orf3b, suggesting a loss of function by the newly adapted virus. Further investigation of orf3b deletion and spike D614G substitution on virulence and infectivity respectively will provide important insights into SARS-CoV-2 evolution.
MeSH term(s)	Amino Acid Sequence ; Cells, Cultured ; Gene Deletion ; Humans ; Interferons/antagonists & inhibitors ; SARS-CoV-2/genetics ; SARS-CoV-2/pathogenicity ; Viral Proteins/chemistry ; Viral Proteins/genetics ; Viral Proteins/immunology
Chemical Substances	Viral Proteins ; Interferons (9008-11-1)
Keywords	covid19
Language	English
Publishing date	2021-02-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2681359-2
ISSN	2222-1751 ; 2222-1751
ISSN (online)	2222-1751
ISSN	2222-1751
DOI	10.1080/22221751.2020.1852892
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: An interferon-integrated mucosal vaccine provides pan-sarbecovirus protection in small animal models

Chun-Kit Yuen / Wan-Man Wong / Long-Fung Mak / Joy-Yan Lam / Lok-Yi Cheung / Derek Tsz-Yin Cheung / Yau-Yee Ng / Andrew Chak-Yiu Lee / Nanshan Zhong / Kwok-Yung Yuen / Kin-Hang Kok

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

2023 Volume 18

Abstract: Abstract A pan-sarbecovirus or pan-betacoronavirus vaccine that can prevent current and potential future beta-coronavirus infections is important for fighting possible future pandemics. Here, we report a mucosal vaccine that cross-protects small animal ... ...

Abstract	Abstract A pan-sarbecovirus or pan-betacoronavirus vaccine that can prevent current and potential future beta-coronavirus infections is important for fighting possible future pandemics. Here, we report a mucosal vaccine that cross-protects small animal models from sarbecoviruses including SARS-CoV-1, SARS-CoV-2 and its variants. The vaccine comprises a live-but-defective SARS-CoV-2 virus that is envelope deficient and has the orf8 segment replaced by interferon-beta, hence named Interferon Beta Integrated SARS-CoV-2 (IBIS) vaccine. Nasal vaccination with IBIS protected mice from lethal homotypic SARS-CoV-2 infection and hamsters from co-housing-mediated transmission of homotypic virus. Moreover, IBIS provided complete protection against heterotypic sarbecoviruses, including SARS-CoV-2 Delta and Omicron variants, and SARS-CoV-1 in both mice and hamsters. Besides inducing a strong lung CD8 + T cell response, IBIS specifically heightened the activation of mucosal virus-specific CD4 + T cells compared to the interferon-null vaccine. The direct production of interferon by IBIS also suppressed virus co-infection of SARS-CoV-2 in human cells, reducing the risk of genetic recombination when using as live vaccines. Altogether, IBIS is a next-generation pan-sarbecovirus vaccine and warrants further clinical investigations.
Keywords	Science ; Q
Subject code	570
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Suppression of SARS-CoV-2 infection in ex-vivo human lung tissues by targeting class III phosphoinositide 3-kinase.

Yuen, Chun-Kit / Wong, Wan-Man / Mak, Long-Fung / Wang, Xiaohui / Chu, Hin / Yuen, Kwok-Yung / Kok, Kin-Hang

Journal of medical virology

2020 Volume 93, Issue 4, Page(s) 2076–2083

Abstract: The novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and caused the coronavirus disease 19 (COVID-19) pandemic due to its high transmissibility and early immunosuppression. Previous studies on ... ...

Abstract	The novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and caused the coronavirus disease 19 (COVID-19) pandemic due to its high transmissibility and early immunosuppression. Previous studies on other betacoronaviruses suggested that betacoronavirus infection is associated with the host autophagy pathway. However, it is unclear whether any components of autophagy or virophagy can be therapeutic targets for COVID-19 treatment. In this report, we examined the antiviral effect of four well-characterized small molecule inhibitors that target the key cellular factors involved in key steps of the autophagy pathway. They include small molecules targeting the ULK1/Atg1 complex involved in the induction stage of autophagy (ULK1 inhibitor SBI0206965), the ATG14/Beclin1/VPS34 complex involved in the nucleation step of autophagy (class III PI3-kinase inhibitor VPS34-IN1), and a widely-used autophagy inhibitor that persistently inhibits class I and temporary inhibits class III PI3-kinase (3-MA) and a clinically approved autophagy inhibitor that suppresses autophagy by inhibiting lysosomal acidification and prevents the formation of autophagolysosome (HCQ). Surprisingly, not all the tested autophagy inhibitors suppressed SARS-CoV-2 infection. We showed that inhibition of class III PI3-kinase involved in the initiation step of both canonical and noncanonical autophagy potently suppressed SARS-CoV-2 at a nano-molar level. In addition, this specific kinase inhibitor VPS34-IN1, and its bioavailable analogue VVPS34-IN1, potently inhibited SARS-CoV-2 infection in ex vivo human lung tissues. Taken together, class III PI3-kinase may be a possible target for COVID-19 therapeutic development.
MeSH term(s)	Adaptor Proteins, Vesicular Transport/antagonists & inhibitors ; Animals ; Antiviral Agents/pharmacology ; Autophagy/drug effects ; Autophagy-Related Protein-1 Homolog/antagonists & inhibitors ; Autophagy-Related Proteins/antagonists & inhibitors ; Chlorocebus aethiops ; Class III Phosphatidylinositol 3-Kinases/antagonists & inhibitors ; Drug Repositioning ; Humans ; In Vitro Techniques ; Intracellular Signaling Peptides and Proteins/antagonists & inhibitors ; Lung/drug effects ; Lung/pathology ; Lung/virology ; Protein Kinase Inhibitors/pharmacology ; Vero Cells ; COVID-19 Drug Treatment
Chemical Substances	ATG14 protein, human ; Adaptor Proteins, Vesicular Transport ; Antiviral Agents ; Autophagy-Related Proteins ; Intracellular Signaling Peptides and Proteins ; Protein Kinase Inhibitors ; Class III Phosphatidylinositol 3-Kinases (EC 2.7.1.137) ; Autophagy-Related Protein-1 Homolog (EC 2.7.11.1) ; ULK1 protein, human (EC 2.7.11.1)
Keywords	covid19
Language	English
Publishing date	2020-10-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.26583
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Article ; Online: Massive Stokes shift in 12-coordinate Ce(NO2)

Luo, Yuxia / Hau, Chun-Kit / Yeung, Yau Yuen / Wong, Ka-Leung / Shiu, Kwok Keung / Tanner, Peter A

Scientific reports

2018 Volume 8, Issue 1, Page(s) 16557

Abstract: ... The ... ...

Abstract	The Ce
Language	English
Publishing date	2018-11-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-34889-4
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Article ; Online: Cyclization, Decyclization, and Metallacyclization of Pyridine-Substituted Homopropargylic Alcohols on Ruthenium(II) and Osmium(II) Centers.

Shek, Hau-Lam / Yeung, Chi-Fung / Chung, Lai-Hon / Tse, Man-Kit / Yiu, Shek-Man / Wong, Chun-Yuen

Chemistry (Weinheim an der Bergstrasse, Germany)

2023 Volume 29, Issue 43, Page(s) e202301292

Abstract: Systematic investigations on the reactions between cis-[M(dppm) ...

Abstract	Systematic investigations on the reactions between cis-[M(dppm)
Language	English
Publishing date	2023-06-27
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1478547-X
ISSN	1521-3765 ; 0947-6539
ISSN (online)	1521-3765
ISSN	0947-6539
DOI	10.1002/chem.202301292
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