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  1. Article ; Online: Early vaccine-mediated strain-specific cytokine imbalance induces mild immunopathology during influenza infection.

    Bull, Maireid B / Ma, Fionn Nl / Perera, Liyanage P / Poon, Leo Lm / Valkenburg, Sophie A

    Immunology and cell biology

    2022  Volume 101, Issue 6, Page(s) 514–524

    Abstract: Influenza A viruses (IAVs) exist as distinct serological subtypes, with limited antibody cross reactivity compared with T-cell responses, leading to universal vaccines that elicit robust T-cell responses entering clinical trials to combat pandemic and ... ...

    Abstract Influenza A viruses (IAVs) exist as distinct serological subtypes, with limited antibody cross reactivity compared with T-cell responses, leading to universal vaccines that elicit robust T-cell responses entering clinical trials to combat pandemic and zoonotic outbreaks. Previously we have extensively characterized the viral-vectored universal vaccine, Wyeth/IL-15/5flu, a group 1 hemagglutinin, H5N1-based vaccine using a vaccinia backbone with interleukin (IL)-15. The vaccine elicits robust T-cell responses to provide heterosubtypic protection from lethal infection; however, we have also observed short-term morbidity of vaccinated mice with a disparity between the effects of sublethal infection with group 1 and 2 IAV strains. At day 3 of H3N2 (group 2 IAV) infection, there was a heavily skewed T helper type 1 response in vaccinated infected mice with overproduction of cytokines and reduced chemokines, whereas H1N1 (group 1 IAV) infection had increased innate cellular responses. These findings suggest that increased and early immune activation by T-cell activating vaccines may induce mild immunopathology when there is a mismatch between non-neutralizing antibody and cross-reactive memory T-cell responses leading to exuberant cytokine production. Therefore, to avoid overstimulating proinflammatory immune responses upon infection, universal influenza vaccines that elicit strong T-cell immunity will need a robust cross-reactive antibody response.
    MeSH term(s) Animals ; Mice ; Humans ; Influenza, Human ; Influenza Vaccines ; Orthomyxoviridae Infections ; Cytokines ; Influenza A Virus, H1N1 Subtype ; Influenza A Virus, H5N1 Subtype ; Influenza A Virus, H3N2 Subtype ; Antibodies, Viral
    Chemical Substances Influenza Vaccines ; Cytokines ; Antibodies, Viral
    Language English
    Publishing date 2022-12-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 284057-1
    ISSN 1440-1711 ; 0818-9641
    ISSN (online) 1440-1711
    ISSN 0818-9641
    DOI 10.1111/imcb.12608
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. 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 ... ...

    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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  3. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Next-generation T cell-activating vaccination increases influenza virus mutation prevalence.

    Bull, Maireid B / Gu, Haogao / Ma, Fionn N L / Perera, Liyanage P / Poon, Leo L M / Valkenburg, Sophie A

    Science advances

    2022  Volume 8, Issue 14, Page(s) eabl5209

    Abstract: To determine the potential for viral adaptation to T cell responses, we probed the full influenza virus genome by next-generation sequencing directly ex vivo from infected mice, in the context of an experimental T cell-based vaccine, an H5N1-based viral ... ...

    Abstract To determine the potential for viral adaptation to T cell responses, we probed the full influenza virus genome by next-generation sequencing directly ex vivo from infected mice, in the context of an experimental T cell-based vaccine, an H5N1-based viral vectored vaccinia vaccine Wyeth/IL-15/5Flu, versus the current standard-of-care, seasonal inactivated influenza vaccine (IIV) and unvaccinated conditions. Wyeth/IL-15/5Flu vaccination was coincident with increased mutation incidence and frequency across the influenza genome; however, mutations were not enriched within T cell epitope regions, but high allele frequency mutations within conserved hemagglutinin stem regions and PB2 mammalian adaptive mutations arose. Depletion of CD4
    MeSH term(s) Animals ; Genome, Viral ; Humans ; Influenza A Virus, H5N1 Subtype/genetics ; Influenza Vaccines ; Influenza, Human/prevention & control ; Interleukin-15/genetics ; Mice ; Mutation ; Orthomyxoviridae Infections ; Prevalence ; Vaccination
    Chemical Substances Influenza Vaccines ; Interleukin-15
    Language English
    Publishing date 2022-04-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.abl5209
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: T Cells Targeting SARS-CoV-2: By Infection, Vaccination, and Against Future Variants.

    Nguyen, Thi H O / Cohen, Carolyn A / Rowntree, Louise C / Bull, Maireid B / Hachim, Asmaa / Kedzierska, Katherine / Valkenburg, Sophie A

    Frontiers in medicine

    2021  Volume 8, Page(s) 793102

    Abstract: T cell responses are a key cornerstone to viral immunity to drive high-quality antibody responses, establishing memory for recall and for viral clearance. Inefficient recruitment of T cell responses plays a role in the development of severe COVID-19 and ... ...

    Abstract T cell responses are a key cornerstone to viral immunity to drive high-quality antibody responses, establishing memory for recall and for viral clearance. Inefficient recruitment of T cell responses plays a role in the development of severe COVID-19 and is also represented by reduced cellular responses in men, children, and diversity compared with other epitope-specific subsets and available T cell receptor diversity. SARS-CoV-2-specific T cell responses are elicited by multiple vaccine formats and augmented by prior infection for hybrid immunity. Epitope conservation is relatively well-maintained leading to T cell crossreactivity for variants of concern that have diminished serological responses.
    Language English
    Publishing date 2021-12-24
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2021.793102
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: The Hurdles From Bench to Bedside in the Realization and Implementation of a Universal Influenza Vaccine.

    Valkenburg, Sophie A / Leung, Nancy H L / Bull, Maireid B / Yan, Li-Meng / Li, Athena P Y / Poon, Leo L M / Cowling, Benjamin J

    Frontiers in immunology

    2018  Volume 9, Page(s) 1479

    Abstract: Influenza viruses circulate worldwide causing annual epidemics that have a substantial impact on public health. This is despite vaccines being in use for over 70 years and currently being administered to around 500 million people each year. Improvements ... ...

    Abstract Influenza viruses circulate worldwide causing annual epidemics that have a substantial impact on public health. This is despite vaccines being in use for over 70 years and currently being administered to around 500 million people each year. Improvements in vaccine design are needed to increase the strength, breadth, and duration of immunity against diverse strains that circulate during regular epidemics, occasional pandemics, and from animal reservoirs. Universal vaccine strategies that target more conserved regions of the virus, such as the hemagglutinin (HA)-stalk, or recruit other cellular responses, such as T cells and NK cells, have the potential to provide broader immunity. Many pre-pandemic vaccines in clinical development do not utilize new vaccine platforms but use "tried and true" recombinant HA protein or inactivated virus strategies despite substantial leaps in fundamental research on universal vaccines. Significant hurdles exist for universal vaccine development from bench to bedside, so that promising preclinical data is not yet translating to human clinical trials. Few studies have assessed immune correlates derived from asymptomatic influenza virus infections, due to the scale of a study required to identity these cases. The realization and implementation of a universal influenza vaccine requires identification and standardization of set points of protective immune correlates, and consideration of dosage schedule to maximize vaccine uptake.
    Language English
    Publishing date 2018-07-02
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2018.01479
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection.

    Mentzer, Alexander J / O'Connor, Daniel / Bibi, Sagida / Chelysheva, Irina / Clutterbuck, Elizabeth A / Demissie, Tesfaye / Dinesh, Tanya / Edwards, Nick J / Felle, Sally / Feng, Shuo / Flaxman, Amy L / Karp-Tatham, Eleanor / Li, Grace / Liu, Xinxue / Marchevsky, Natalie / Godfrey, Leila / Makinson, Rebecca / Bull, Maireid B / Fowler, Jamie /
    Alamad, Bana / Malinauskas, Tomas / Chong, Amanda Y / Sanders, Katherine / Shaw, Robert H / Voysey, Merryn / Snape, Matthew D / Pollard, Andrew J / Lambe, Teresa / Knight, Julian C

    Nature medicine

    2022  Volume 29, Issue 1, Page(s) 147–157

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine immunogenicity varies between individuals, and immune responses correlate with vaccine efficacy. Using data from 1,076 participants enrolled in ChAdOx1 nCov-19 vaccine efficacy trials ... ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine immunogenicity varies between individuals, and immune responses correlate with vaccine efficacy. Using data from 1,076 participants enrolled in ChAdOx1 nCov-19 vaccine efficacy trials in the United Kingdom, we found that inter-individual variation in normalized antibody responses against SARS-CoV-2 spike and its receptor-binding domain (RBD) at 28 days after first vaccination shows genome-wide significant association with major histocompatibility complex (MHC) class II alleles. The most statistically significant association with higher levels of anti-RBD antibody was HLA-DQB1*06 (P = 3.2 × 10
    MeSH term(s) Humans ; Alleles ; Antibodies, Viral ; Breakthrough Infections ; ChAdOx1 nCoV-19 ; COVID-19/genetics ; COVID-19/prevention & control ; COVID-19 Vaccines/immunology ; Histocompatibility Antigens Class II ; Immunogenicity, Vaccine ; SARS-CoV-2 ; Vaccination
    Chemical Substances Antibodies, Viral ; ChAdOx1 nCoV-19 (B5S3K2V0G8) ; COVID-19 Vaccines ; Histocompatibility Antigens Class II
    Language English
    Publishing date 2022-10-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/s41591-022-02078-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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