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2. Sensitive Detection of SARS-CoV-2-Specific Antibodies in Dried Blood Spot Samples

Author

Morley, Gabriella L., Taylor, Stephen, Jossi, Sian, Perez-Toledo, Marisol, Faustini, Sian E., Marcial-Juarez, Edith, Shields, Adrian M., Goodall, Margaret, Allen, Joel D., Watanabe, Yasunori, Newby, Maddy L., Crispin, Max, Drayson, Mark T., Cunningham, Adam F., Richter, Alex G., and OShea, Matthew K.

Subjects
Blood -- Medical examination, Serodiagnosis -- Methods, Health
Abstract

A confirmed diagnosis of acute coronavirus disease (COVID-19) depends on the detection of RNA from the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In contrast, although serologic testing [...]

Published
2020
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3. SARS-CoV-2 infection is associated with anti-desmoglein 2 autoantibody detection

Author

Ward, Kerensa E, primary, Steadman, Lora, additional, Karim, Abid R, additional, Reynolds, Gary M, additional, Pugh, Matthew, additional, Chua, Winnie, additional, Faustini, Sian E, additional, Veenith, Tonny, additional, Thwaites, Ryan S, additional, Openshaw, Peter J M, additional, Drayson, Mark T, additional, Shields, Adrian M, additional, Cunningham, Adam F, additional, Wraith, David C, additional, and Richter, Alex G, additional

Published
2023
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5. Determinants of Antibody Responses to SARS-CoV-2 Vaccines: Population-Based Longitudinal Study (COVIDENCE UK)

Author

Jolliffe, David A., primary, Faustini, Sian E., additional, Holt, Hayley, additional, Perdek, Natalia, additional, Maltby, Sheena, additional, Talaei, Mohammad, additional, Greenig, Matthew, additional, Vivaldi, Giulia, additional, Tydeman, Florence, additional, Symons, Jane, additional, Davies, Gwyneth A., additional, Lyons, Ronan A., additional, Griffiths, Christopher J., additional, Kee, Frank, additional, Sheikh, Aziz, additional, Shaheen, Seif O., additional, Richter, Alex G., additional, and Martineau, Adrian R., additional

Published
2022
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6. Vitamin D Supplementation Does Not Influence SARS-CoV-2 Vaccine Efficacy or Immunogenicity: Sub-Studies Nested within the CORONAVIT Randomised Controlled Trial

Author

Jolliffe, David A., primary, Vivaldi, Giulia, additional, Chambers, Emma S., additional, Cai, Weigang, additional, Li, Wenhao, additional, Faustini, Sian E., additional, Gibbons, Joseph M., additional, Pade, Corinna, additional, Coussens, Anna K., additional, Richter, Alex G., additional, McKnight, Áine, additional, and Martineau, Adrian R., additional

Published
2022
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7. Vitamin D status: a U-shaped relationship for SARS-CoV-2 seropositivity in UK healthcare workers

Author

Lugg, Sebastian T, primary, Mackay, William R, additional, Faniyi, Aduragbemi A, additional, Faustini, Sian E, additional, Webster, Craig, additional, Duffy, Joanne E, additional, Hewison, Martin, additional, Shields, Adrian M, additional, Parekh, Dhruv, additional, Richter, Alex G, additional, Scott, Aaron, additional, and Thickett, David R, additional

Published
2022
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8. SARS-CoV-2 Spike- and Nucleoprotein-Specific Antibodies Induced After Vaccination or Infection Promote Classical Complement Activation

Author

Lamerton, Rachel E., primary, Marcial-Juarez, Edith, additional, Faustini, Sian E., additional, Perez-Toledo, Marisol, additional, Goodall, Margaret, additional, Jossi, Siân E., additional, Newby, Maddy L., additional, Chapple, Iain, additional, Dietrich, Thomas, additional, Veenith, Tonny, additional, Shields, Adrian M., additional, Harper, Lorraine, additional, Henderson, Ian R., additional, Rayes, Julie, additional, Wraith, David C., additional, Watson, Steve P., additional, Crispin, Max, additional, Drayson, Mark T., additional, Richter, Alex G., additional, and Cunningham, Adam F., additional

Published
2022
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9. SARS‐CoV‐2‐specific IgG1/IgG3 but not IgM in children with Pediatric Inflammatory Multi‐System Syndrome

Author

Perez‐toledo, Marisol, Faustini, Sian E., Jossi, Sian E., Shields, Adrian M., Marcial‐juarez, Edith, Kanthimathinathan, Hari Krishnan, Allen, Joel D., Watanabe, Yasunori, Goodall, Margaret, Willcox, Benjamin E., Willcox, Carrie R., Salim, Mahboob, Wraith, David C., Veenith, Tonny V., Syrimi, Eleni, Drayson, Mark T., Jyothish, Deepthi, Al‐abadi, Eslam, Chikermane, Ashish, Welch, Steven B., Masilamani, Kavitha, Hackett, Scott, Crispin, Max, Scholefield, Barnaby R., Cunningham, Adam F., Richter, Alex G., and Genuneit, Jon

Subjects
2019-20 coronavirus outbreak, biology, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, medicine.disease, Virology, Immunoglobulin G, Systemic inflammatory response syndrome, Immunoglobulin M, Pediatrics, Perinatology and Child Health, biology.protein, Immunology and Allergy, Medicine, business, Letters to the Editor, Letter to the Editor
Abstract

During the COVID-19 outbreak, reports have surfaced of children who present with features of a multisystem inflammatory syndrome with overlapping features of Kawasaki disease and toxic shock syndrome - Paediatric Inflammatory Multisystem Syndrome- temporally associated with SARS-CoV-2 pandemic (PIMS-TS). Initial reports find that many of the children are PCR-negative for SARS-CoV-2, so it is difficult to confirm whether this syndrome is a late complication of viral infection in an age group largely spared the worst consequences of this infection, or if this syndrome reflects enhanced surveillance.Children hospitalised for symptoms consistent with PIMS-TS between 28 April and 8 May 2020, and who were PCR-negative for SARS-CoV-2, were tested for antibodies to viral spike glycoprotein using an ELISA test.Eight patients (age range 7-14 years, 63% male) fulfilled case-definition for PIMS-TS during the study period. Six of the eight patients required admission to intensive care. All patients exhibited significant IgG and IgA responses to viral spike glycoprotein. Further assessment showed that the IgG isotypes detected in children with PIMS-TS were of the IgG1 and IgG3 subclasses, a distribution similar to that observed in samples from hospitalised adult COVID-19 patients. In contrast, IgG2 and IgG4 were not detected in children or adults. IgM was not detected in children, which contrasts with adult hospitalised adult COVID-19 patients of whom all had positive IgM responses.Strong IgG antibody responses can be detected in PCR-negative children with PIMS-TS. The low detection rate of IgM in these patients is consistent with infection having occurred weeks previously and that the syndrome onset occurs well after the control of SARS-CoV-2 viral load. This implies that the disease is largely immune-mediated. Lastly, this indicates that serology can be an appropriate diagnostic tool in select patient groups.

Published
2021

10. SARS-CoV-2 vaccine responses following CD20-depletion treatment in patients with haematological and rheumatological disease: a West Midlands Research Consortium study

Author

Shields, Adrian M, primary, Venkatachalam, Srinivasan, additional, Shafeek, Salim, additional, Paneesha, Shankara, additional, Ford, Mark, additional, Sheeran, Tom, additional, Kelly, Melanie, additional, Qureshi, Iman, additional, Salhan, Beena, additional, Karim, Farheen, additional, De Silva, Neelakshi, additional, Stones, Jacqueline, additional, Lee, Sophie, additional, Khawaja, Jahanzeb, additional, Kaudlay, Praveen Kumar, additional, Whitmill, Richard, additional, Kakepoto, Ghulam Nabi, additional, Parry, Helen M, additional, Moss, Paul, additional, Faustini, Sian E, additional, Richter, Alex G, additional, Drayson, Mark T, additional, and Basu, Supratik, additional

Published
2021
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11. Vaccine Efficacy after Rituximab Exposure: First Interim Analysis of Virtue Project on Behalf of West Midlands Research Consortium, UK

Author

Shields, Adrian M, primary, Venkatachalam, Srinivasan, additional, Paneesha, Shankara, additional, Ford, Mark, additional, Sheeran, Tom, additional, Kelly, Melanie, additional, Karim, Farheen, additional, Qureshi, Iman, additional, Salhan, Beena, additional, DeSilva, Neelakshi, additional, Stones, Jacqueline, additional, Lee, Sophie, additional, Khawaja, Jahanzeb, additional, Kaudlay, Praveen Kumar, additional, Whitmill, Richard, additional, Nabikakepoto, Ghulam, additional, Faustini, Sian E, additional, Richter, Alex G, additional, Drayson, Mark T, additional, and Basu, Supratik, additional

Published
2021
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12. Response to COVID-19 Vaccines in Patients Receiving Intensified Post-ASCT Therapy with Daratumumab, Lenalidomide, Bortezomib (Dara-VR) Due to Ultra-High Risk (UHiR) Newly Diagnosed Myeloma (NDMM) or Primary Plasma Cell Leukemia (pPCL): Exploratory Analysis of the UK Optimum/Muknine Trial

Author

Jenner, Matthew W, primary, Hall, Andrew, additional, Faustini, Sian E, additional, Pitchford, Alexandra, additional, de Tute, Ruth M., additional, Roberts, Sadie, additional, Ingleson, Emma, additional, Bowles, Kristian M, additional, Garg, Mamta, additional, Lokare, Anand, additional, Messiou, Christina, additional, Jackson, Graham, additional, Pratt, Guy, additional, Cook, Gordon, additional, Owen, Roger G, additional, Brown, Sarah R, additional, Drayson, Mark T, additional, and Kaiser, Martin F., additional

Published
2021
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13. Serological responses to SARS-CoV-2 following non-hospitalised infection: clinical and ethnodemographic features associated with the magnitude of the antibody response

Author

Shields, Adrian M, primary, Faustini, Sian E, additional, Perez-Toledo, Marisol, additional, Jossi, Sian, additional, Allen, Joel D, additional, Al-Taei, Saly, additional, Backhouse, Claire, additional, Dunbar, Lynsey A, additional, Ebanks, Daniel, additional, Emmanuel, Beena, additional, Faniyi, Aduragbemi A, additional, Garvey, Mark, additional, Grinbergs, Annabel, additional, McGinnell, Golaleh, additional, O'Neill, Joanne, additional, Watanabe, Yasunori, additional, Crispin, Max, additional, Wraith, David C, additional, Cunningham, Adam F, additional, Drayson, Mark T, additional, and Richter, Alex G, additional

Published
2021
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14. Establishing the prevalence of common tissue-specific autoantibodies following severe acute respiratory syndrome coronavirus 2 infection

Author

Richter, Alex G, primary, Shields, Adrian M, additional, Karim, Abid, additional, Birch, David, additional, Faustini, Sian E, additional, Steadman, Lora, additional, Ward, Kerensa, additional, Plant, Timothy, additional, Reynolds, Gary, additional, Veenith, Tonny, additional, Cunningham, Adam F, additional, Drayson, Mark T, additional, and Wraith, David C, additional

Published
2021
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15. Development of a high‐sensitivity ELISA detecting IgG, IgA and IgM antibodies to the SARS‐CoV‐2 spike glycoprotein in serum and saliva

Author

Faustini, Sian E., primary, Jossi, Sian E., additional, Perez‐Toledo, Marisol, additional, Shields, Adrian M., additional, Allen, Joel D., additional, Watanabe, Yasunori, additional, Newby, Maddy L., additional, Cook, Alex, additional, Willcox, Carrie R., additional, Salim, Mahboob, additional, Goodall, Margaret, additional, Heaney, Jennifer L., additional, Marcial‐Juarez, Edith, additional, Morley, Gabriella L., additional, Torlinska, Barbara, additional, Wraith, David C., additional, Veenith, Tonny V., additional, Harding, Stephen, additional, Jolles, Stephen, additional, Ponsford, Mark J., additional, Plant, Tim, additional, Huissoon, Aarnoud, additional, O'Shea, Matthew K., additional, Willcox, Benjamin E., additional, Drayson, Mark T., additional, Crispin, Max, additional, Cunningham, Adam F., additional, and Richter, Alex G., additional

Published
2021
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17. Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study.

Author

Shields, Adrian M., Faustini, Sian E., Hill, Harriet J., Al-Taei, Saly, Tanner, Chloe, Ashford, Fiona, Workman, Sarita, Moreira, Fernando, Verma, Nisha, Wagg, Hollie, Heritage, Gail, Campton, Naomi, Stamataki, Zania, Drayson, Mark T., Klenerman, Paul, Thaventhiran, James E. D., Elkhalifa, Shuayb, Goddard, Sarah, Johnston, Sarah, and Huissoon, Aarnoud

Subjects
ANTIBODY formation, PRIMARY immunodeficiency diseases, SARS-CoV-2, COVID-19 vaccines, IMMUNIZATION
Abstract

Background: Patients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity. Objectives: To determine the immunogenicity of the third primary SARS-CoV-2 immunisation in a heterogeneous cohort of patients with antibody deficiency. Methods: Participants enrolled in the COV-AD study were sampled before and after their third vaccine dose. Serological and cellular responses were determined using ELISA, livevirus neutralisation and ELISPOT assays. Results: Following a two-dose schedule, 100% of healthy controls mounted a serological response to SARS-CoV-2 vaccination, however, 38.6% of individuals with antibody deficiency remained seronegative. A third primary SARS-CoV-2 vaccine significantly increased anti-spike glycoprotein antibody seroprevalence from 61.4% to 76.0%, the magnitude of the antibody response, its neutralising capacity and induced seroconversion in individuals who were seronegative after two vaccine doses. Vaccine-induced serological responses were broadly cross-reactive against the SARS-CoV-2 B.1.1.529 variant of concern, however, seroprevalence and antibody levels remained significantly lower than healthy controls. No differences in serological responses were observed between individuals who received AstraZeneca ChAdOx1 nCoV-19 and Pfizer BioNTech 162b2 during their initial two-dose vaccine schedule. SARS-CoV-2 infectionnaive participants who had received a heterologous vaccine as a third dose were significantly more likely to have a detectable T cell response following their third vaccine dose (61.5% vs 11.1%). Conclusion: These data support the widespread use of third primary immunisations to enhance humoral immunity against SARS-CoV-2 in individuals with antibody deficiency. [ABSTRACT FROM AUTHOR]

Published
2022
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18. Production and efficacy of a low-cost recombinant pneumococcal protein polysaccharide conjugate vaccine

Author

Herbert, Jenny A, Kay, Emily J, Faustini, Sian E, Richter, Alex, Abouelhadid, Sherif, Cuccui, Jon, Wren, Brendan, and Mitchell, Timothy J

Subjects
Vaccines, Synthetic/administration & dosage, Glycoengineering, Polysaccharides, Bacterial/immunology, Article, Pneumococcal Vaccines, Mice, Conjugate vaccine, Escherichia coli, Animals, Technology, Pharmaceutical, Pneumococcal Vaccines/administration & dosage, Streptococcus pneumoniae/immunology, Pneumonia, Pneumococcal/immunology, Vaccines, Synthetic, Vaccines, Conjugate, Protein glycan coupling technology, Polysaccharides, Bacterial, Pneumonia, Pneumonia, Pneumococcal, Vaccines, Conjugate/administration & dosage, Escherichia coli/genetics, Disease Models, Animal, Streptococcus pneumoniae, Treatment Outcome, Technology, Pharmaceutical/economics, Female
Abstract

Highlights • Pneumococcal glycoconjugate vaccines produced in E. coli are protective in mice. • Protection correlates with opsonic antibody levels. • This is a cheaper way to produce conjugate vaccines., Streptococcus pneumoniae is the leading cause of bacterial pneumonia. Although this is a vaccine preventable disease, S. pneumoniae still causes over 1 million deaths per year, mainly in children under the age of five. The biggest disease burden is in the developing world, which is mainly due to unavailability of vaccines due to their high costs. Protein polysaccharide conjugate vaccines are given routinely in the developed world to children to induce a protective antibody response against S. pneumoniae. One of these vaccines is Prevnar13, which targets 13 of the 95 known capsular types. Current vaccine production requires growth of large amounts of the 13 serotypes, and isolation of the capsular polysaccharide that is then chemically coupled to a protein, such as the diphtheria toxoid CRM197, in a multistep expensive procedure. In this study, we design, purify and produce novel recombinant pneumococcal protein polysaccharide conjugate vaccines in Escherichia coli, which act as mini factories for the low-cost production of conjugate vaccines. Recombinant vaccine efficacy was tested in a murine model of pneumococcal pneumonia; ability to protect against invasive disease was compared to that of Prevnar13. This study provides the first proof of principle that protein polysaccharide conjugate vaccines produced in E. coli can be used to prevent pneumococcal infection. Vaccines produced in this manner may provide a low-cost alternative to the current vaccine production methodology.

Published
2018

20. SARS-CoV-2 vaccine responses following CD20-depletion treatment in patients with haematological and rheumatological disease: a West Midlands Research Consortium study.

Author

Shields, Adrian M, Venkatachalam, Srinivasan, Shafeek, Salim, Paneesha, Shankara, Ford, Mark, Sheeran, Tom, Kelly, Melanie, Qureshi, Iman, Salhan, Beena, Karim, Farheen, De Silva, Neelakshi, Stones, Jacqueline, Lee, Sophie, Khawaja, Jahanzeb, Kaudlay, Praveen Kumar, Whitmill, Richard, Kakepoto, Ghulam Nabi, Parry, Helen M, Moss, Paul, and Faustini, Sian E

Subjects
VACCINE effectiveness, COVID-19 vaccines, BOOSTER vaccines, CONSORTIA, B cells, IMMUNE reconstitution inflammatory syndrome, AUTOIMMUNE diseases
Abstract

B-cell-depleting agents are among the most commonly used drugs to treat haemato-oncological and autoimmune diseases. They rapidly induce a state of peripheral B-cell aplasia with the potential to interfere with nascent vaccine responses, particularly to novel antigens. We have examined the relationship between B-cell reconstitution and SARS-CoV-2 vaccine responses in two cohorts of patients previously exposed to B-cell-depleting agents: a cohort of patients treated for haematological B-cell malignancy and another treated for rheumatological disease. B-cell depletion severely impairs vaccine responsiveness in the first 6 months after administration: SARS-CoV-2 antibody seroprevalence was 42.2% and 33.3% in the haemato-oncological patients and rheumatology patients, respectively and 22.7% in patients vaccinated while actively receiving anti-lymphoma chemotherapy. After the first 6 months, vaccine responsiveness significantly improved during early B-cell reconstitution; however, the kinetics of reconstitution was significantly faster in haemato-oncology patients. The AstraZeneca ChAdOx1 nCoV-19 vaccine and the Pfizer BioNTech 162b vaccine induced equivalent vaccine responses; however, shorter intervals between vaccine doses (<1 m) improved the magnitude of the antibody response in haeamto-oncology patients. In a subgroup of haemato-oncology patients, with historic exposure to B-cell-depleting agents (>36 m previously), vaccine non-responsiveness was independent of peripheral B-cell reconstitution. The findings have important implications for primary vaccination and booster vaccination strategies in individuals clinically vulnerable to SARS-CoV-2. B cell depleting drugs including rituximab are commonly used to treat haematological malignancy and autoimmune diseases but may impair the immunological response to vaccination. This study investigates SARS-CoV-2 vaccine responses in individuals with haematological and rheumatological disease with previously exposure to B cell depleting agents. Vaccination within the first 6 months of B cell depletion is associated with significant impairment of vaccine responsiveness; however, rheumatology and haemato-oncological patients display different kinetics of B cell reconstitution corresponding to differential vaccine responsiveness over time. [ABSTRACT FROM AUTHOR]

Published
2022
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21. Humoral immunity to memory antigens and pathogens is maintained in patients with chronic kidney disease

Author

Wall, Nadezhda A., primary, Dominguez-Medina, C. Coral, additional, Faustini, Sian E., additional, Cook, Charlotte N., additional, McClean, Andrew, additional, Jesky, Mark D., additional, Perez-Toledo, Marisol, additional, Morgan, Matthew D., additional, Richter, Alexandra G., additional, Ferro, Charles J., additional, Cockwell, Paul, additional, Moss, Paul A., additional, Henderson, Ian R., additional, Harper, Lorraine, additional, and Cunningham, Adam F., additional

Published
2018
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23. Vitamin D status and seroconversion for COVID-19 in UK healthcare workers.

Author

Faniyi AA, Lugg ST, Faustini SE, Webster C, Duffy JE, Hewison M, Shields A, Nightingale P, Richter AG, and Thickett DR

Subjects
Adult, Female, Humans, Male, Middle Aged, United Kingdom, COVID-19 blood, Health Personnel, Seroconversion, Vitamin D blood
Abstract

Competing Interests: Conflict of interest: A.A. Faniyi has nothing to disclose. Conflict of interest: S.T. Lugg has nothing to disclose. Conflict of interest: S.E. Faustini has nothing to disclose. Conflict of interest: C. Webster has nothing to disclose. Conflict of interest: J.E. Duffy has nothing to disclose. Conflict of interest: M. Hewison reports personal fees for lectures from Thornton Ross, outside the submitted work. Conflict of interest: A. Shields has nothing to disclose. Conflict of interest: P. Nightingale has nothing to disclose. Conflict of interest: A.G. Richter has nothing to disclose. Conflict of interest: D.R. Thickett reports personal fees for lectures from Thornton Ross, outside the submitted work.

Published
2021
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