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  1. Article ; Online: Accelerated waning of the humoral response to COVID-19 vaccines in obesity.

    van der Klaauw, Agatha A / Horner, Emily C / Pereyra-Gerber, Pehuén / Agrawal, Utkarsh / Foster, William S / Spencer, Sarah / Vergese, Bensi / Smith, Miriam / Henning, Elana / Ramsay, Isobel D / Smith, Jack A / Guillaume, Stephane M / Sharpe, Hayley J / Hay, Iain M / Thompson, Sam / Innocentin, Silvia / Booth, Lucy H / Robertson, Chris / McCowan, Colin /
    Kerr, Steven / Mulroney, Thomas E / O'Reilly, Martin J / Gurugama, Thevinya P / Gurugama, Lihinya P / Rust, Maria A / Ferreira, Alex / Ebrahimi, Soraya / Ceron-Gutierrez, Lourdes / Scotucci, Jacopo / Kronsteiner, Barbara / Dunachie, Susanna J / Klenerman, Paul / Park, Adrian J / Rubino, Francesco / Lamikanra, Abigail A / Stark, Hannah / Kingston, Nathalie / Estcourt, Lise / Harvala, Heli / Roberts, David J / Doffinger, Rainer / Linterman, Michelle A / Matheson, Nicholas J / Sheikh, Aziz / Farooqi, I Sadaf / Thaventhiran, James E D

    Nature medicine

    2023  Volume 29, Issue 5, Page(s) 1146–1154

    Abstract: Obesity is associated with an increased risk of severe Coronavirus Disease 2019 (COVID-19) infection and mortality. COVID-19 vaccines reduce the risk of serious COVID-19 outcomes; however, their effectiveness in people with obesity is incompletely ... ...

    Abstract Obesity is associated with an increased risk of severe Coronavirus Disease 2019 (COVID-19) infection and mortality. COVID-19 vaccines reduce the risk of serious COVID-19 outcomes; however, their effectiveness in people with obesity is incompletely understood. We studied the relationship among body mass index (BMI), hospitalization and mortality due to COVID-19 among 3.6 million people in Scotland using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) surveillance platform. We found that vaccinated individuals with severe obesity (BMI > 40 kg/m
    MeSH term(s) Humans ; COVID-19 Vaccines ; Obesity, Morbid ; Longitudinal Studies ; Prospective Studies ; COVID-19/epidemiology ; COVID-19/prevention & control ; SARS-CoV-2 ; Obesity/epidemiology ; Antibodies, Neutralizing ; Antibodies, Viral ; Vaccination
    Chemical Substances COVID-19 Vaccines ; Antibodies, Neutralizing ; Antibodies, Viral
    Language English
    Publishing date 2023-05-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/s41591-023-02343-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Age-associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade.

    Yam-Puc, Juan Carlos / Hosseini, Zhaleh / Horner, Emily C / Gerber, Pehuén Pereyra / Beristain-Covarrubias, Nonantzin / Hughes, Robert / Lulla, Aleksei / Rust, Maria / Boston, Rebecca / Ali, Magda / Fischer, Katrin / Simmons-Rosello, Edward / O'Reilly, Martin / Robson, Harry / Booth, Lucy H / Kahanawita, Lakmini / Correa-Noguera, Andrea / Favara, David / Ceron-Gutierrez, Lourdes /
    Keller, Baerbel / Craxton, Andrew / Anderson, Georgina S F / Sun, Xiao-Ming / Elmer, Anne / Saunders, Caroline / Bermperi, Areti / Jose, Sherly / Kingston, Nathalie / Mulroney, Thomas E / Piñon, Lucia P G / Chapman, Michael A / Grigoriadou, Sofia / MacFarlane, Marion / Willis, Anne E / Patil, Kiran R / Spencer, Sarah / Staples, Emily / Warnatz, Klaus / Buckland, Matthew S / Hollfelder, Florian / Hyvönen, Marko / Döffinger, Rainer / Parkinson, Christine / Lear, Sara / Matheson, Nicholas J / Thaventhiran, James E D

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 3292

    Abstract: Age-associated B cells (ABC) accumulate with age and in individuals with different immunological disorders, including cancer patients treated with immune checkpoint blockade and those with inborn errors of immunity. Here, we investigate whether ABCs from ...

    Abstract Age-associated B cells (ABC) accumulate with age and in individuals with different immunological disorders, including cancer patients treated with immune checkpoint blockade and those with inborn errors of immunity. Here, we investigate whether ABCs from different conditions are similar and how they impact the longitudinal level of the COVID-19 vaccine response. Single-cell RNA sequencing indicates that ABCs with distinct aetiologies have common transcriptional profiles and can be categorised according to their expression of immune genes, such as the autoimmune regulator (AIRE). Furthermore, higher baseline ABC frequency correlates with decreased levels of antigen-specific memory B cells and reduced neutralising capacity against SARS-CoV-2. ABCs express high levels of the inhibitory FcγRIIB receptor and are distinctive in their ability to bind immune complexes, which could contribute to diminish vaccine responses either directly, or indirectly via enhanced clearance of immune complexed-antigen. Expansion of ABCs may, therefore, serve as a biomarker identifying individuals at risk of suboptimal responses to vaccination.
    MeSH term(s) Humans ; Immunity, Humoral ; Immune Checkpoint Inhibitors ; COVID-19 Vaccines ; COVID-19/prevention & control ; SARS-CoV-2 ; Vaccination ; Antigen-Antibody Complex ; Antibodies, Viral
    Chemical Substances Immune Checkpoint Inhibitors ; COVID-19 Vaccines ; Antigen-Antibody Complex ; Antibodies, Viral
    Language English
    Publishing date 2023-06-27
    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/s41467-023-38810-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens.

    Moore, Shona C / Kronsteiner, Barbara / Longet, Stephanie / Adele, Sandra / Deeks, Alexandra S / Liu, Chang / Dejnirattisai, Wanwisa / Reyes, Laura Silva / Meardon, Naomi / Faustini, Sian / Al-Taei, Saly / Tipton, Tom / Hering, Luisa M / Angyal, Adrienn / Brown, Rebecca / Nicols, Alexander R / Dobson, Susan L / Supasa, Piyada / Tuekprakhon, Aekkachai /
    Cross, Andrew / Tyerman, Jessica K / Hornsby, Hailey / Grouneva, Irina / Plowright, Megan / Zhang, Peijun / Newman, Thomas A H / Nell, Jeremy M / Abraham, Priyanka / Ali, Mohammad / Malone, Tom / Neale, Isabel / Phillips, Eloise / Wilson, Joseph D / Murray, Sam M / Zewdie, Martha / Shields, Adrian / Horner, Emily C / Booth, Lucy H / Stafford, Lizzie / Bibi, Sagida / Wootton, Daniel G / Mentzer, Alexander J / Conlon, Christopher P / Jeffery, Katie / Matthews, Philippa C / Pollard, Andrew J / Brown, Anthony / Rowland-Jones, Sarah L / Mongkolsapaya, Juthathip / Payne, Rebecca P / Dold, Christina / Lambe, Teresa / Thaventhiran, James E D / Screaton, Gavin / Barnes, Eleanor / Hopkins, Susan / Hall, Victoria / Duncan, Christopher J A / Richter, Alex / Carroll, Miles / de Silva, Thushan I / Klenerman, Paul / Dunachie, Susanna / Turtle, Lance

    Med (New York, N.Y.)

    2023  Volume 4, Issue 3, Page(s) 191–215.e9

    Abstract: Background: Both infection and vaccination, alone or in combination, generate antibody and T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the maintenance of such responses-and hence protection from ... ...

    Abstract Background: Both infection and vaccination, alone or in combination, generate antibody and T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the maintenance of such responses-and hence protection from disease-requires careful characterization. In a large prospective study of UK healthcare workers (HCWs) (Protective Immunity from T Cells in Healthcare Workers [PITCH], within the larger SARS-CoV-2 Immunity and Reinfection Evaluation [SIREN] study), we previously observed that prior infection strongly affected subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination.
    Methods: Here, we report longer follow-up of 684 HCWs in this cohort over 6-9 months following two doses of BNT162b2 or AZD1222 (Oxford/AstraZeneca) vaccination and up to 6 months following a subsequent mRNA booster vaccination.
    Findings: We make three observations: first, the dynamics of humoral and cellular responses differ; binding and neutralizing antibodies declined, whereas T and memory B cell responses were maintained after the second vaccine dose. Second, vaccine boosting restored immunoglobulin (Ig) G levels; broadened neutralizing activity against variants of concern, including Omicron BA.1, BA.2, and BA.5; and boosted T cell responses above the 6-month level after dose 2. Third, prior infection maintained its impact driving larger and broader T cell responses compared with never-infected people, a feature maintained until 6 months after the third dose.
    Conclusions: Broadly cross-reactive T cell responses are well maintained over time-especially in those with combined vaccine and infection-induced immunity ("hybrid" immunity)-and may contribute to continued protection against severe disease.
    Funding: Department for Health and Social Care, Medical Research Council.
    MeSH term(s) Humans ; COVID-19 Vaccines ; BNT162 Vaccine ; ChAdOx1 nCoV-19 ; Prospective Studies ; COVID-19 ; SARS-CoV-2 ; Vaccines ; Antibodies, Neutralizing ; Health Personnel ; Immunity, Humoral
    Chemical Substances COVID-19 Vaccines ; BNT162 Vaccine ; ChAdOx1 nCoV-19 (B5S3K2V0G8) ; Vaccines ; Antibodies, Neutralizing
    Language English
    Publishing date 2023-02-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ISSN 2666-6340
    ISSN (online) 2666-6340
    DOI 10.1016/j.medj.2023.02.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Age-Associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade

    Yam-Puc, Juan Carlos / Hosseini, Zhaleh / Horner, Emily C / Gerber, Pehuen Pereira / Beristain-Covarrubias, Nonantzin / Hughes, Robert / Rust, Maria / Boston, Rebecca / Ali, Magda / Simmons Rosello, Edward / O'Reilly, Martin / Robson, Harry / Booth, Lucy H / Kahanawita, Lakmini / Grigoriadou, Sofia / Correa-Noguera, Andrea / Ceron-Guiterez, Lourdes / Mulroney, Thomas / Lulla, Aleksei /
    Fischer, Katrin / Craxton, Andrew / Anderson, Georgina SF / Sun, Xiao-Ming / Elmer, Anne / Saunders, Caroline / Bermperi, Areti / Jose, Sherly / Chapman, Mike / MacFarlane, Marion / Willis, Anne E / Patil, Kiran R / Hollfelder, Florian / Hyvonen, Marko / CITIID-NIHR COVID-19 BioResource Collaboration / Spencer, Sarah / Staples, Emily / Buckland, Matthew S / Doffinger, Rainer / Parkinson, Christine / Lear, Sara / Matheson, Nicholas J / Thaventhiran, James ED

    medRxiv

    Abstract: The effect of immune checkpoint blockade on COVID-19 immunity is unclear. In this study, we determine whether immune checkpoint blockade expanded age-associated B cells (ABCs) are similar to those present in other conditions, and whether they enhance or ... ...

    Abstract The effect of immune checkpoint blockade on COVID-19 immunity is unclear. In this study, we determine whether immune checkpoint blockade expanded age-associated B cells (ABCs) are similar to those present in other conditions, and whether they enhance or detract from the COVID-19 vaccine responses. First, we use single cell RNA sequencing (scRNAseq) to show that ABCs arising from distinct aetiologies have common transcriptional profiles and may be further subdivided according to expression of genes associated with different immune functions, including the autoimmune regulator (AIRE). Next, we perform detailed longitudinal profiling of the COVID-19 vaccination response in patients. Finally, we show that high pre-vaccination ABC frequency correlates with decreased levels of antigen-specific memory B cells, and reduced magnitude and longevity of neutralising capacity against authentic SARS-CoV-2 virus. Expansion of ABCs is a biomarker for individuals with cancer requiring additional or more frequent booster immunisation against COVID-19.
    Keywords covid19
    Language English
    Publishing date 2022-09-20
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2022.09.17.22280033
    Database COVID19

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  5. Article ; Online: Accelerated waning of the humoral response to SARS-CoV-2 vaccines in obesity

    van der Klaauw, Agatha A. / Horner, Emily C. / Pereyra-Gerber, Pehuen / Agrawal, Utkarsh / Foster, William S. / Spencer, Sarah / Vergese, Bensi / Smith, Miriam E. / Henning, Elana / Ramsay, Isobel D. / Smith, Jack A. / Guillaume, Stephane M. / Sharpe, Hayley J. / Hay, Iain M. / Thompson, Sam / Innocentin, Silvia / Booth, Lucy H / Robertson, Chris / McCowan, Colin /
    Mulroney, Thomas E / O'Reilly, Martin J / Guragama, Thevinya P / Guragama, Lihinya P / Rust, Maria A / Ferreira, Alex / Ebrahimi, Soraya / Ceron-Gutierrez, Lourdes / Scotucci, Jacopo / Kronsteiner, Barbara / Dunachie, Susanna J. / Klenerman, Paul / PITCH Consortium / Park, Adrian J. / Rubino, Francesco / Stark, Hannah / Kingson, Nathalie / Doffinger, Rainer / Linterman, Michelle A. / Matheson, Nicholas J. / Sheikh, Aziz / Farooqi, I. Sadaf / Thaventhiran, James E.

    medRxiv

    Abstract: Obesity is associated with an increased risk of severe Covid-19. However, the effectiveness of SARS-CoV-2 vaccines in people with obesity is unknown. Here we studied the relationship between body mass index (BMI), hospitalization and mortality due to ... ...

    Abstract Obesity is associated with an increased risk of severe Covid-19. However, the effectiveness of SARS-CoV-2 vaccines in people with obesity is unknown. Here we studied the relationship between body mass index (BMI), hospitalization and mortality due to Covid-19 amongst 3.5 million people in Scotland. Vaccinated people with severe obesity (BMI>40 kg/m2) were significantly more likely to experience hospitalization or death from Covid-19. Excess risk increased with time since vaccination. To investigate the underlying mechanisms, we conducted a prospective longitudinal study of the immune response in a clinical cohort of vaccinated people with severe obesity. Compared with normal weight controls, six months after their second vaccine dose, significantly more people with severe obesity had unquantifiable titres of neutralizing antibody against authentic SARS-CoV-2 virus, reduced frequencies of antigen-experienced SARS-CoV-2 Spike-binding B cells, and a dissociation between anti-Spike antibody levels and neutralizing capacity. Neutralizing capacity was restored by a third dose of vaccine, but again declined more rapidly in people with severe obesity. We demonstrate that waning of SARS-CoV-2 vaccine-induced humoral immunity is accelerated in people with severe obesity and associated with increased hospitalization and mortality from breakthrough infections. Given the prevalence of obesity, our findings have significant implications for global public health.
    Keywords covid19
    Language English
    Publishing date 2022-06-14
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2022.06.09.22276196
    Database COVID19

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    Inter-library loan at ZB MED

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  6. Article ; Online: Evolution of long-term hybrid immunity in healthcare workers after different COVID-19 vaccination regimens: a longitudinal observational cohort study

    Moore, Shona C / Kronsteiner, Barbara / Longet, Stephanie / Adele, Sandra / Deeks, Alexandra S / Liu, Chang / Dejnirattisai, Wanwisa / Silva Reyes, Laura / Meardon, Naomi / Faustini, Sian / Al-Taei, Saly / Tipton, Tom / Hering, Luisa M / Angyal, Adrienn / Brown, Rebecca / Nicols, Alexander R / Dobson, Susan L / Supasa, Piyada / Tuekprakhon, Aekkachai /
    Cross, Andrew / Tyerman, Jessica K / Hornsby, Hailey / Grouneva, Irina / Plowright, Megan / Zhang, Peijun / Newman, Thomas A.H. / Nell, Jeremy M. / Abraham, Priyanka / Ali, Mohammad / Malone, Tom / Neale, Isabel / Phillips, Eloise / Wilson, Joseph D. / Shields, Adrian / Horner, Emily C. / Booth, Lucy H. / Stafford, Lizzie / Bibi, Sagida / Wootton, Daniel G. / Mentzer, Alexander J. / Conlon, Christopher P. / Jeffery, Katie / Matthews, Philippa C. / Pollard, Andrew J. / Brown, Anthony / Rowland-Jones, Sarah L. / Mongkolsapaya, Juthathip / Payne, Rebecca P. / Dold, Christina / Lambe, Teresa / Thaventhiran, James E.D. / Screaton, Gavin / Barnes, Eleanor / Hopkins, Susan / Hall, Victoria / Duncan, Christopher JA / Richter, Alex Richter / Carroll, Miles / de Silva, Thushan I. / Klenerman, Paul / Dunachie, Susanna / Turtle, Lance

    medRxiv

    Abstract: Both infection and vaccination, alone or in combination, generate antibody and T cell responses against SARS–CoV–2. However, the maintenance of such responses – and hence protection from disease – requires careful characterisation. In a large prospective ...

    Abstract Both infection and vaccination, alone or in combination, generate antibody and T cell responses against SARS–CoV–2. However, the maintenance of such responses – and hence protection from disease – requires careful characterisation. In a large prospective study of UK healthcare workers (PITCH, within the larger SIREN study) we previously observed that prior infection impacted strongly on subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination. Here, we report longer follow up of 684 HCWs in this cohort over 6–9 months following two doses of BNT162b2 or AZ1222 (Oxford/AstraZeneca) vaccination and following a subsequent BNT162b2 booster vaccination. We make three important observations: Firstly, the dynamics of humoral and cellular responses differ; binding and neutralising antibodies declined whereas T and B cell responses were better maintained after the second vaccine dose. Secondly, vaccine boosting restored IgG levels to post second dose levels and broadened neutralising activity against variants of concern including omicron BA.1, alongside further boosting of T cell responses. Thirdly, prior infection maintained its impact driving larger T cell responses compared to never infected people, including after the third dose. In conclusion, the maintenance of T cell responses in time and against variants of concern may account for continued protection against severe disease.
    Keywords covid19
    Language English
    Publishing date 2022-06-07
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2022.06.06.22275865
    Database COVID19

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