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Article ; Online: Transmissibility and transmission of respiratory viruses.

Leung, Nancy H L

2021 Volume 19, Issue 8, Page(s) 528–545

Abstract: Human respiratory virus infections lead to a spectrum of respiratory symptoms and disease severity, contributing to substantial morbidity, mortality and economic losses worldwide, as seen in the COVID-19 pandemic. Belonging to diverse families, ... ...

Abstract	Human respiratory virus infections lead to a spectrum of respiratory symptoms and disease severity, contributing to substantial morbidity, mortality and economic losses worldwide, as seen in the COVID-19 pandemic. Belonging to diverse families, respiratory viruses differ in how easy they spread (transmissibility) and the mechanism (modes) of transmission. Transmissibility as estimated by the basic reproduction number (R
MeSH term(s)	Aerosols ; COVID-19/transmission ; COVID-19/virology ; Humans ; Hygiene ; Personal Protective Equipment ; SARS-CoV-2/physiology
Chemical Substances	Aerosols
Language	English
Publishing date	2021-03-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2139054-X
ISSN	1740-1534 ; 1740-1526
ISSN (online)	1740-1534
ISSN	1740-1526
DOI	10.1038/s41579-021-00535-6
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Article ; Online: Upper Respiratory Infections in Schools and Childcare Centers Reopening after COVID-19 Dismissals, Hong Kong.

Fong, Min Whui / Leung, Nancy H L / Cowling, Benjamin J / Wu, Peng

Emerging infectious diseases

2021 Volume 27, Issue 5, Page(s) 1525–1527

Abstract: A large number of common cold outbreaks in Hong Kong schools and childcare centers during October-November 2020 led to territorywide school dismissals. Increased susceptibility to rhinoviruses during prolonged school closures and dismissals for ... ...

Abstract	A large number of common cold outbreaks in Hong Kong schools and childcare centers during October-November 2020 led to territorywide school dismissals. Increased susceptibility to rhinoviruses during prolonged school closures and dismissals for coronavirus disease and varying effectiveness of nonpharmaceutical interventions may have heightened transmission of cold-causing viruses after school attendance resumed.
MeSH term(s)	COVID-19 ; Disease Outbreaks ; Hong Kong/epidemiology ; Humans ; SARS-CoV-2 ; Schools
Language	English
Publishing date	2021-02-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1380686-5
ISSN	1080-6059 ; 1080-6040
ISSN (online)	1080-6059
ISSN	1080-6040
DOI	10.3201/eid2705.210277
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Article ; Online: Influenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children.

Jia, Janice Z / Cohen, Carolyn A / Gu, Haogao / McLean, Milla R / Varadarajan, Raghavan / Bhandari, Nisha / Peiris, Malik / Leung, Gabriel M / Poon, Leo L M / Tsang, Tim / Chung, Amy W / Cowling, Benjamin J / Leung, Nancy H L / Valkenburg, Sophie A

Nature communications

2024 Volume 15, Issue 1, Page(s) 3210

Abstract: Cross-reactive antibodies with Fc receptor (FcR) effector functions may mitigate pandemic virus impact in the absence of neutralizing antibodies. In this exploratory study, we use serum from a randomized placebo-controlled trial of seasonal trivalent ... ...

Abstract	Cross-reactive antibodies with Fc receptor (FcR) effector functions may mitigate pandemic virus impact in the absence of neutralizing antibodies. In this exploratory study, we use serum from a randomized placebo-controlled trial of seasonal trivalent influenza vaccination in children (NCT00792051) conducted at the onset of the 2009 H1N1 pandemic (pH1N1) and monitored for infection. We found that seasonal vaccination increases pH1N1 specific antibodies and FcR effector functions. Furthermore, prospective baseline antibody profiles after seasonal vaccination, prior to pH1N1 infection, show that unvaccinated uninfected children have elevated ADCC effector function, FcγR3a and FcγR2a binding antibodies to multiple pH1N1 proteins, past seasonal and avian (H5, H7 and H9) strains. Whereas, children that became pH1N1 infected after seasonal vaccination have antibodies focussed to seasonal strains without FcR functions, and greater aggregated HA-specific profiles for IgM and IgG3. Modeling to predict infection susceptibility, ranked baseline hemagglutination antibody inhibition as the highest contributor to lack of pH1N1 infection, in combination with features that include pH1-IgG1, H1-stem responses and FcR binding to seasonal vaccine and pH1 proteins. Thus, seasonal vaccination can have benefits against pandemic influenza viruses, and some children already have broadly reactive antibodies with Fc potential without vaccination and may be considered 'elite influenza controllers'.
MeSH term(s)	Child ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza, Human/epidemiology ; Influenza, Human/prevention & control ; Prospective Studies ; Antibodies, Viral ; Antibodies, Neutralizing ; Immunoglobulin G ; Influenza Vaccines
Chemical Substances	Antibodies, Viral ; Antibodies, Neutralizing ; Immunoglobulin G ; Influenza Vaccines
Language	English
Publishing date	2024-04-13
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-47590-0
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Article: High-throughput sequencing-based neutralization assay reveals how repeated vaccinations impact titers to recent human H1N1 influenza strains.

Loes, Andrea N / Tarabi, Rosario Araceli L / Huddleston, John / Touyon, Lisa / Wong, Sook San / Cheng, Samuel M S / Leung, Nancy H L / Hannon, William W / Bedford, Trevor / Cobey, Sarah / Cowling, Benjamin J / Bloom, Jesse D

bioRxiv : the preprint server for biology

2024

Abstract: The high genetic diversity of influenza viruses means that traditional serological assays have too low throughput to measure serum antibody neutralization titers against all relevant strains. To overcome this challenge, we have developed a sequencing- ... ...

Abstract	The high genetic diversity of influenza viruses means that traditional serological assays have too low throughput to measure serum antibody neutralization titers against all relevant strains. To overcome this challenge, we have developed a sequencing-based neutralization assay that simultaneously measures titers against many viral strains using small serum volumes via a workflow similar to traditional neutralization assays. The key innovation is to incorporate unique nucleotide barcodes into the hemagglutinin (HA) genomic segment, and then pool viruses with numerous different barcoded HA variants and quantify infectivity of all of them simultaneously using next-generation sequencing. With this approach, a single researcher performed the equivalent of 2,880 traditional neutralization assays (80 serum samples against 36 viral strains) in approximately one month. We applied the sequencing-based assay to quantify the impact of influenza vaccination on neutralization titers against recent human H1N1 strains for individuals who had or had not also received a vaccine in the previous year. We found that the viral strain specificities of the neutralizing antibodies elicited by vaccination vary among individuals, and that vaccination induced a smaller increase in titers for individuals who had also received a vaccine the previous year-although the titers six months after vaccination were similar in individuals with and without the previous-year vaccination. We also identified a subset of individuals with low titers to a subclade of recent H1N1 even after vaccination. This study demonstrates the utility of high-throughput sequencing-based neutralization assays that enable titers to be simultaneously measured against many different viral strains. We provide a detailed experimental protocol (DOI: https://dx.doi.org/10.17504/protocols.io.kqdg3xdmpg25/v1) and a computational pipeline (https://github.com/jbloomlab/seqneut-pipeline) for the sequencing-based neutralization assays to facilitate the use of this method by others.
Language	English
Publishing date	2024-03-09
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.08.584176
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Article ; Online: Upper Respiratory Infections in Schools and Childcare Centers Reopening after COVID-19 Dismissals, Hong Kong

Min Whui Fong / Nancy H.L. Leung / Benjamin J. Cowling / Peng Wu

Emerging Infectious Diseases, Vol 27, Iss 5, Pp 1525-

2021 Volume 1527

Abstract: A large number of common cold outbreaks in Hong Kong schools and childcare centers during October–November 2020 led to territorywide school dismissals. Increased susceptibility to rhinoviruses during prolonged school closures and dismissals for ... ...

Abstract	A large number of common cold outbreaks in Hong Kong schools and childcare centers during October–November 2020 led to territorywide school dismissals. Increased susceptibility to rhinoviruses during prolonged school closures and dismissals for coronavirus disease and varying effectiveness of nonpharmaceutical interventions may have heightened transmission of cold-causing viruses after school attendance resumed.
Keywords	acute respiratory illness ; coronavirus disease ; COVID-19 ; outbreaks ; respiratory infections ; rhinovirus ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Centers for Disease Control and Prevention
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Universally Immune: How Infection Permissive Next Generation Influenza Vaccines May Affect Population Immunity and Viral Spread.

Bull, Maireid B / Cohen, Carolyn A / Leung, Nancy H L / Valkenburg, Sophie A

Viruses

2021 Volume 13, Issue 9

Abstract: Next generation influenza vaccines that target conserved epitopes are becoming a clinical reality but still have challenges to overcome. Universal next generation vaccines are considered a vital tool to combat future pandemic viruses and have the ... ...

Abstract	Next generation influenza vaccines that target conserved epitopes are becoming a clinical reality but still have challenges to overcome. Universal next generation vaccines are considered a vital tool to combat future pandemic viruses and have the potential to vastly improve long-term protection against seasonal influenza viruses. Key vaccine strategies include HA-stem and T cell activating vaccines; however, they could have unintended effects for virus adaptation as they recognise the virus after cell entry and do not directly block infection. This may lead to immune pressure on residual viruses. The potential for immune escape is already evident, for both the HA stem and T cell epitopes, and mosaic approaches for pre-emptive immune priming may be needed to circumvent key variants. Live attenuated influenza vaccines have not been immunogenic enough to boost T cells in adults with established prior immunity. Therefore, viral vectors or peptide approaches are key to harnessing T cell responses. A plethora of viral vector vaccines and routes of administration may be needed for next generation vaccine strategies that require repeated long-term administration to overcome vector immunity and increase our arsenal against diverse influenza viruses.
MeSH term(s)	Adenovirus Vaccines ; Animals ; Antibodies, Viral ; CD8-Positive T-Lymphocytes/immunology ; Epitopes ; Humans ; Influenza Vaccines/immunology ; Influenza, Human ; Orthomyxoviridae/immunology ; Orthomyxoviridae Infections ; T-Lymphocytes/immunology ; Vaccination ; Vaccines, Attenuated/immunology
Chemical Substances	Adenovirus Vaccines ; Antibodies, Viral ; Epitopes ; Influenza Vaccines ; Vaccines, Attenuated
Language	English
Publishing date	2021-09-06
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13091779
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Article ; Online: Slow Waning of Antibodies Following BNT162b2 as a Third Dose in Adults Who Had Previously Received 2 Doses of Inactivated Vaccine.

Cowling, Benjamin J / Cheng, Samuel M S / Martín-Sánchez, Mario / Au, Niki Y M / Chan, Karl C K / Li, John K C / Fung, Lison W C / Luk, Leo L H / Tsang, Leo C H / Ip, Dennis K M / Poon, Leo L M / Leung, Gabriel M / Peiris, J S Malik / Leung, Nancy H L

The Journal of infectious diseases

2022 Volume 227, Issue 2, Page(s) 251–255

Abstract: We administered BNT162b2 as a third dose to 314 adults aged ≥30 years who had previously received 2 doses of inactivated vaccine. We collected blood samples before the third dose and again after 1 month and 6 months, and found robust antibody responses ... ...

Abstract	We administered BNT162b2 as a third dose to 314 adults aged ≥30 years who had previously received 2 doses of inactivated vaccine. We collected blood samples before the third dose and again after 1 month and 6 months, and found robust antibody responses to the ancestral strain at 6 months after receipt of BNT162b2. Antibody responses to Omicron BA.2 by live virus neutralization were weaker after the third dose and had declined to a low level by 6 months.
MeSH term(s)	Adult ; Humans ; BNT162 Vaccine ; Vaccines, Inactivated ; Antibodies ; Antibodies, Viral
Chemical Substances	BNT162 Vaccine ; Vaccines, Inactivated ; Antibodies ; Antibodies, Viral
Language	English
Publishing date	2022-09-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiac380
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Article ; Online: Controversy around airborne versus droplet transmission of respiratory viruses: implication for infection prevention.

Shiu, Eunice Y C / Leung, Nancy H L / Cowling, Benjamin J

Current opinion in infectious diseases

2019 Volume 32, Issue 4, Page(s) 372–379

Abstract: Purpose of review: Health agencies recommend transmission-based precautions, including contact, droplet and airborne precautions, to mitigate transmission of respiratory viruses in healthcare settings. There is particular controversy over the importance ...

Abstract	Purpose of review: Health agencies recommend transmission-based precautions, including contact, droplet and airborne precautions, to mitigate transmission of respiratory viruses in healthcare settings. There is particular controversy over the importance of aerosol transmission and whether airborne precautions should be recommended for some respiratory viruses. Here, we review the current recommendations of transmission-based precautions and the latest evidence on the aerosol transmission of respiratory viruses. Recent findings: Viral nucleic acids, and in some instances viable viruses, have been detected in aerosols in the air in healthcare settings for some respiratory viruses such as seasonal and avian influenza viruses, Middle East respiratory syndrome-coronavirus and respiratory syncytial virus. However, current evidences are yet to demonstrate that these viruses can effectively spread via airborne route between individuals, or whether preventive measures in airborne precautions would be effective. Summary: Studies that use transmission events as outcome to demonstrate human-to-human transmission over the aerosol route or quantitative measurement of infectious respiratory viruses in the air are needed to evaluate the infectiousness of respiratory viruses over the aerosol route. When a respiratory virus in concern only leads to disease with low severity, airborne precautions are not likely to be justified.
MeSH term(s)	Air Microbiology ; Animals ; Cross Infection/epidemiology ; Cross Infection/prevention & control ; Cross Infection/transmission ; Cross Infection/virology ; Humans ; Particulate Matter/adverse effects ; Respiratory Tract Infections/epidemiology ; Respiratory Tract Infections/prevention & control ; Respiratory Tract Infections/transmission ; Respiratory Tract Infections/virology
Chemical Substances	Particulate Matter
Keywords	covid19
Language	English
Publishing date	2019-07-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	645085-4
ISSN	1473-6527 ; 1535-3877 ; 0951-7375 ; 1355-834X
ISSN (online)	1473-6527 ; 1535-3877
ISSN	0951-7375 ; 1355-834X
DOI	10.1097/QCO.0000000000000563
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Zs.A 2462: Show issues

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Article: Universally Immune: How Infection Permissive Next Generation Influenza Vaccines May Affect Population Immunity and Viral Spread

Bull, Maireid B. / Cohen, Carolyn A. / Leung, Nancy H.L. / Valkenburg, Sophie A.

Viruses. 2021 Sept. 06, v. 13, no. 9

2021

Abstract	Next generation influenza vaccines that target conserved epitopes are becoming a clinical reality but still have challenges to overcome. Universal next generation vaccines are considered a vital tool to combat future pandemic viruses and have the potential to vastly improve long-term protection against seasonal influenza viruses. Key vaccine strategies include HA-stem and T cell activating vaccines; however, they could have unintended effects for virus adaptation as they recognise the virus after cell entry and do not directly block infection. This may lead to immune pressure on residual viruses. The potential for immune escape is already evident, for both the HA stem and T cell epitopes, and mosaic approaches for pre-emptive immune priming may be needed to circumvent key variants. Live attenuated influenza vaccines have not been immunogenic enough to boost T cells in adults with established prior immunity. Therefore, viral vectors or peptide approaches are key to harnessing T cell responses. A plethora of viral vector vaccines and routes of administration may be needed for next generation vaccine strategies that require repeated long-term administration to overcome vector immunity and increase our arsenal against diverse influenza viruses.
Keywords	T-lymphocytes ; epitopes ; immunity ; influenza ; live vaccines ; pandemic ; peptides ; viruses
Language	English
Dates of publication	2021-0906
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13091779
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Investigation of CD4 and CD8 T cell-mediated protection against influenza A virus in a cohort study.

Tsang, Tim K / Lam, Kwok-Tai / Liu, Yinping / Fang, Vicky J / Mu, Xiaofeng / Leung, Nancy H L / Peiris, J S Malik / Leung, Gabriel M / Cowling, Benjamin J / Tu, Wenwei

BMC medicine

2022 Volume 20, Issue 1, Page(s) 230

Abstract: Background: The protective effect of T cell-mediated immunity against influenza virus infections in natural settings remains unclear, especially in seasonal epidemics.: Methods: To explore the potential of such protection, we analyzed the blood ... ...

Abstract	Background: The protective effect of T cell-mediated immunity against influenza virus infections in natural settings remains unclear, especially in seasonal epidemics. Methods: To explore the potential of such protection, we analyzed the blood samples collected longitudinally in a community-based study and covered the first wave of pandemic H1N1 (pH1N1), two subsequent pH1N1 epidemics, and three seasonal H3N2 influenza A epidemics (H3N2) for which we measured pre-existing influenza virus-specific CD4 and CD8 T cell responses by intracellular IFN-γ staining assay for 965 whole blood samples. Results: Based on logistic regression, we found that higher pre-existing influenza virus-specific CD4 and CD8 T cell responses were associated with lower infection odds for corresponding subtypes. Every fold increase in H3N2-specific CD4 and CD8 T cells was associated with 28% (95% CI 8%, 44%) and 26% (95% CI 8%, 41%) lower H3N2 infection odds, respectively. Every fold increase in pre-existing seasonal H1N1 influenza A virus (sH1N1)-specific CD4 and CD8 T cells was associated with 28% (95% CI 11%, 41%) and 22% (95% CI 8%, 33%) lower pH1N1 infection odds, respectively. We observed the same associations for individuals with pre-epidemic hemagglutination inhibition (HAI) titers < 40. There was no correlation between pre-existing influenza virus-specific CD4 and CD8 T cell response and HAI titer. Conclusions: We demonstrated homosubtypic and cross-strain protection against influenza infections was associated with T cell response, especially CD4 T cell response. These protections were independent of the protection associated with HAI titer. Therefore, T cell response could be an assessment of individual and population immunity for future epidemics and pandemics, in addition to using HAI titer.
MeSH term(s)	Antibodies, Viral ; CD8-Positive T-Lymphocytes ; Cohort Studies ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza A Virus, H3N2 Subtype ; Influenza A virus ; Influenza Vaccines ; Influenza, Human/epidemiology
Chemical Substances	Antibodies, Viral ; Influenza Vaccines
Language	English
Publishing date	2022-07-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2131669-7
ISSN	1741-7015 ; 1741-7015
ISSN (online)	1741-7015
ISSN	1741-7015
DOI	10.1186/s12916-022-02429-7
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