Investigation of proven vaccine breakthrough by SARS-CoV-2 variants in established UK healthcare worker cohorts: SIREN consortium & PITCH Plus Pathway

Lead Research Organisation: Public Health England
Department Name: National Infection Service

Abstract

This project builds on the established PHE SIREN and associated cohorts (PITCH and HICC) working with leading immunologists and scientists to improve understanding of the immune response to infection and vaccines and study in detail those individuals who have proven vaccine breakthrough. These studies are following more than 45,000 healthcare workers, 94% of whom have received two doses of vaccine, and will assess their immune system response to COVID-19 infections and vaccinations.

Understanding the immune response is essential to determine who is most at risk of infections after vaccination, and also for vaccine developers who can target key components of the immune response effectively for future boost vaccines. The adaptive immune system has two major components - B-cells and T-cells. The B-cells produce antibodies that can be detected after previous infection or vaccination. We will be studying two that are expressed against proteins from the virus - the Spike (S) and Nucleocapsid (N) proteins that are measured using assays that can give us the quantity of each present and also a measurement of neutralising or "sterilising" immunity - assessing how well an individual's blood can kill or neutralise either a live SARS-CoV-2 virus or a lab created replica. The T-cells directly kill virus infected cells by releasing proteins known as cytokines, which can signal to other cells and provide instructions to the immune system on its strength and range of response.

The research is focused on key areas:
1. Why do some people get reinfections or infections after vaccination?
2. In individuals who get infections after vaccination, can we identify which parts of their immune system are not working to provide immune protection?
3. How long does this immunity from vaccinations last and how does it differ with different vaccines?
4. How does the immune system respond to booster doses of vaccination?
5. How do changes in the SARS-CoV-2 virus genetic make-up cause evasion of the immune response?
6. What are the differences that can be detected in the human genetic code that are associated with different immune responses to the virus and vaccination?

We will assess these questions using blood from key groups of individuals recruited into our cohort studies to assess the immune response. We will study:
a) individuals who have a re-infection (a second infection after having a previous confirmed infection) and one or two doses of vaccination and
b) individuals who develop an infection after two doses of vaccine.

We can do this effectively because all individuals who are in the study have PCR tests every two weeks and regular blood tests for antibodies that are stored for future analysis. In addition, for individuals who develop infections after vaccination, we will discuss with them in more detail to determine whether they could have a functional problem with their immune system, take specific medications that could prevent their immune system from responding and seek their consent to take additional blood tests to perform detailed analysis of their immune response to COVID. This will involve analysis of their blood tests before and after the infection episode and we will ask if they would like to participate in genetic analysis of their DNA code to see if there are particular mutations in their DNA code that might predict a poor response to vaccination.

We will seek to do this scientifically using specific study designs that will compare individuals who acquire an infection after vaccination to others who do not get infections, matched to age, sex, ethnicity, and co-morbidities. The T and B-cell immune responses will be compared to determine if there are key detectable differences between these groups.

Technical Summary

The SIREN Consortium aims to investigate the correlates of immunity against SARS-CoV-2 post-vaccination, including the durability of the immune response in healthcare workers (HCW).
The study uses the strengths of the largest global cohort study (N~45,000) with regular serological and alternate weekly SARS-CoV-2 PCR testing.
This additional funding enables detailed immunological nested case-control studies where cases are infections post-vaccination and compared to appropriately matched controls. 75 proven vaccine breakthrough cases have already been identified and daily alerts for new infections are in place.

It will assess host and pathogen factors related to infections post-vaccination with the PITCH Plus pathway
1. Anti-S and anti-N neutralising antibodies against the current SARS-CoV-2 variants of concern, using validated pseudovirus microneutralisation (pMN) assay and live virus MN & Tcell memory responses, by IFNG Elispot and T cell proliferation assay
2. The durability of binding and quantification S and N antibody, neutralising antibody and T-cell responses in recipients of different vaccines and vaccination schedules
3. Genotype to phenotype mapping including centralised genomic surveillance for all cases, analysis and exploratory assessment to better define the correlates of humoral and cellular immunity for novel mutations/ emerging variants.
4. Clinical immunology consultation: individuals with post-vaccine infections will be invited to a telephone consultation to review their medical history, have bloods undertaken to assess underlying health conditions, associated immunodeficiency and the humoral and cellular immune system.
5. Human genotyping with consent we will obtain and store genetic material from vaccine breakthrough cases to enable future assessment of known single nucleotide polymorphisms and where necessary whole genome sequencing for associations with suboptimal vaccine response and immunodeficiency.

Publications

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Ragonnet-Cronin M (2023) Generation of SARS-CoV-2 escape mutations by monoclonal antibody therapy in Nature Communications

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Escudero-Pérez B (2023) Immune correlates of protection for SARS-CoV-2, Ebola and Nipah virus infection in Frontiers in Immunology

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Hall V (2022) Protection against SARS-CoV-2 after Covid-19 Vaccination and Previous Infection. in The New England journal of medicine

 
Guideline Title COVID-19: the green book, chapter 14a
Description Citation in the UK vaccine "green book"
Geographic Reach National 
Policy Influence Type Citation in clinical guidelines
Impact This paper described enhanced immunogenicity of COVID vaccine with increasing time between vaccine doses. This supported government policy to space out the vaccine doses in early 2021.
URL https://www.gov.uk/government/publications/covid-19-the-green-book-chapter-14a
 
Description Impact of omicron variants on the T cell response to spike
Geographic Reach National 
Policy Influence Type Participation in a guidance/advisory committee
Impact This information supported national response by informing key decision makers on the immune response to omicron.
 
Description Levels of neutralisation required to prevent infection
Geographic Reach National 
Policy Influence Type Participation in a guidance/advisory committee
Impact This work is feeding into policy advice through advisory groups and a working comittee.
 
Description Member of COVID-19 nMABs and Antivirals Access and Policy National Expert Group (DHSC)
Geographic Reach National 
Policy Influence Type Participation in a guidance/advisory committee
Impact Likely to be reducing mortality in the most vulnerable groups.
 
Description Member of UK-HSA SARS-CoV-2 variant technical group
Geographic Reach National 
Policy Influence Type Participation in a guidance/advisory committee
Impact The risk assessments from this committee have been used to set government policy for COVID lockdowns and administration of vaccines
URL https://www.gov.uk/government/publications/investigation-of-sars-cov-2-variants-technical-briefings
 
Description NICE therapeutics panel
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
Impact Ensured correct advice on neutralising monoclonals wrt variants.
 
Description Participant Involvement Panel
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact The work was highlighted in the upcoming NCSi Public and Participant Involvement Cases Studies report.
 
Description Presentation of results to Department of Health and Social Care
Geographic Reach National 
Policy Influence Type Participation in a guidance/advisory committee
Impact Quantitative information on changes in vaccine-induced antibody and T cell responses with omicron variant compared to delta and Wuhan strain.
 
Description Report - Patient and public involvement in COVID-19 research: bridging the gap between theory and practice
Geographic Reach National 
Policy Influence Type Contribution to new or improved professional practice
Impact Increased awareness of the role of patient and participation involvement in research
URL https://www.covidvaccineresearch.org/sites/default/files/2022-12/NCSI%20PPI%20Report.pdf
 
Description SIREN scientific and surveillance outputs
Geographic Reach National 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact Efficient dissemination of SIREN's scientific and surveillance outputs has informed policy decisions during the COVID-19 pandemic.
 
Description Scientific Advisor (Immunologist) to UK's New & Emerging Respiratory Virus Advisory Group (NERVTAG)
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a guidance/advisory committee
URL https://www.gov.uk/government/groups/new-and-emerging-respiratory-virus-threats-advisory-group
 
Description Scientific Advisor to the Scottish Parliament
Geographic Reach National 
Policy Influence Type Contribution to a national consultation/review
Impact Every 3 weeks I (along with 2 other Scientific Advisors) brief the Scottish Parliament's COVID-19 Recovery Committee, which consists of 6 MSPs, and this has directly influenced policy decisions for COVID-19 in Scotland including vaccine passports, face coverings, hospitality opening, social distancing, and spending. Topics I have been asked to give an opinion on include: - Duration of immunity from vaccines and infection - Predictions of harm from omicron variant - Vaccine hesitancy and how to tackle - Vaccine safety in pregnancy - Impact of vaccines on viral transmission - Impact of masks on viral transmission - How to improve morale and effectiveness in healthcare sector - Risks to national logistics from workforce absences
URL https://www.parliament.scot/chamber-and-committees/committees/current-and-previous-committees/sessio...
 
Description Variant Technical Group
Geographic Reach Multiple continents/international 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact The knowledge and risk assessments on emerging variants is used to inform government policy on travel, COVID-19 restrictions, healthcare resources and workforce planning.
URL https://www.gov.uk/government/publications/investigation-of-sars-cov-2-variants-technical-briefings
 
Description Broadly neutralising antibodies after vaccination
Amount £1,000,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 04/2023 
End 04/2028
 
Description EME NIHR
Amount £1,800,000 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 03/2023 
End 04/2026
 
Description MRC clinician scientist fellowship
Amount £1,940,331 (GBP)
Funding ID MR/X006751/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 04/2023 
End 04/2028
 
Description PITCH2 - Protective Immunity through T Cells in Healthcare workers 2
Amount £2,023,708 (GBP)
Funding ID MR/X009297/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 12/2022 
End 11/2024
 
Description PITCH2 - Protective Immunity through T Cells in Healthcare workers 2
Amount £1,999,350 (GBP)
Funding ID MR/X009297/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2023 
End 01/2025
 
Description SIREN Winter Pressures Study
Amount £34,378 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 01/2023 
End 03/2023
 
Description Southeast Asia initiative to combat SARS-CoV-2 variants SEACOVARIANTS
Amount £2,999,984 (GBP)
Funding ID 226120/Z/22/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2023 
End 02/2026
 
Title Founded PITCH International 
Description I have brought together researchers in UK, Indonesia, India, Bangladesh, Vietnam, Thailand, Kenya and UAE to study the T cell response to SARS-CoV-2 following vaccination and infection. I supported an outstanding Vietnamese colleague to lead a successful £3million application to Wellcome for SEACOVARIANTs - capacity building to understanding the biological impact of SARS-CoV-2 
Type Of Material Improvements to research infrastructure 
Year Produced 2021 
Provided To Others? No  
Impact I assembled and chaired a symposium at the Joint International Tropical Medicine Meeting in Bangkok, Thailand (virtual) in 2021, with speakers from Bangladesh, Kenya and Vietnam reporting research my lab has supported by collaboration with methods and reagents. In 2022 I supported an outstanding Vietnamese colleague to lead a successful £3million application to Wellcome for SEACOVARIANTs - capacity building to understanding the biological impact of SARS-CoV-2 from 2023-26 
URL https://www.jitmm.com/Home
 
Title Pseudotyped virus microneutralisation (pMN) assay for SARSCoV-2 and antigenic variants 
Description This method is a surrogate of the SARSCoV-2 live virus neutralisation aassay. The pMN uses a recombinant lentivirus pseudotype which expresses the Spike protein of the SARSCoV-2 ancestral Wuhan virus or aany of the variants that emerged during this pandemic. This psudotypee virus is non replicative and caarried a luciferase reportre gene which serves to measure the levels of activ infection aftr incubaton with susceptible cells. When the pseudotype virus is incubated with plasma samples containing virus neutralising antibodies there is a reduction of th luciferase signal that is quantifiable. Virus neutralising antibodies were detected and quantified by a pseudotype-based neutralisation assay based on a lentiviral system that enables the generation of replication-defective recombinant human immunodeficiency virus (HIV) displaying the Spike protein of SARS-CoV-2 on their viral envelope, as previously described (see references from the published paprs). Briefly, HEK293T cells were seeded in 10 sqcm cell culture dishes at a density to achieve 70% confluency after 24 hours for next day transfection. HEK293T cells were maintained in DMEM (Dulbecco Minimum Essential Medium) containing 10% foetal bovine serum and 1% penicillin/streptomycin, at 37°C and 5% CO2. Cell maintenance was done by three cell passages per week. On the day of transfection, the culture medium was replaced with fresh complete DMEM. Cells were transfected with 1000 ng of pcDNA-SARS-CoV-2 Spike plasmid, 1000ng of HIV 8.91 gag/pol plasmid and 1500ng of pCSFLW luciferase plasmid, using FuGENE HD (Promega, UK), at a 1:3 ratio (plasmid:FuGENE HD). The culture media was harvested 48 hours post-transfection and filtered through a 0.45µm filter. The filtered pseudotype virus (PV) was aliquoted, titrated and stored at -80°C. Titration of PVs was carried out in a 96 well white plate typically using doubling serial dilutions. Pre-transfected HEK293T target cells expressing human ACE2 and TMPRSS2 were seeded at 10000 cells per well and plates were incubated for 48 hours prior to the addition of Bright-Glo reagent (Promega, UK) and reading the result in a luminometer. For detecting and quantifying neutralising antibodies, serial doubling dilutions of the plasma samples in complete DMEM were performed from an initial 1/40 dilution. SARS-CoV-2 PVs were added at 5x100000 - 5x1000000 RLU/ml in each well and the plates incubated for 1 hour in at 37°C, 5% CO2 incubator. Post incubation, pre-transfected HEK293T target cells expressing human ACE2 and TMPRSS2 were seeded at 10000 cells per well and plates were incubated for 48 hours prior to the addition of Bright-Glo reagent and assaying using a luminometer. In addition to the test sample dilutions, all test runs included dilution series of an external calibrant (NIBSC 20/162) or an internal calibrant (HICC Serum 2) and a single dilution of a positive control per plate (NIBSC 20/136). All samples were tested in duplicate and the average of the OD values determined. The IC50 values of each sample dilution series were determined and expressed as relative potency respect to the Internal or External Calibrant which enabled the expression of results in International Units using the WHO International Standard 20/136 as a primary calibrator. 
Type Of Material Technology assay or reagent 
Year Produced 2021 
Provided To Others? Yes  
Impact This assay has been successfully used by us and others to quantify virus neutralising antibodies against ARSCoV-2 in plasma samples from individuals or experimental exposed to SARSCoV-2. The assay correlates very weell with the live virus neutralisation assy but can be performed undere BSL-2 biosafety measures. Also, the assay can be adapted quickly to measuring specific VNAb against new emergent vaariants. So far we have developed this assay for the following SARSC0V-2 strains: Wuhan, Alpha, Beta, Gamma, Delta, Omicron and BA2. VNAb is the first bio-marker identified to predict reasonably likely in vaccinatd and SARSCoV-2 convalescent individuals the outcome of infection upon exposure / re-exposure to the virus. The continuous emergence of new variants of concern (VOC) represents a challenge for measuring the breadth of the virus neutraalising antibody response in SARS-CoV-2 vaccinated and / or infected individuals. The live virus neutralisation test involves the use of a panel of viruses representing the latest emerging strains or variants, which often differ from each other by aa limited number of residues in the Spike amino acid sequence. When these viruses are grown in tissue culture they can experiment further mutations that misrepresent the true antigenic characteristics of the Spike of the natural variant. This problem is overcome by using the pseutyped virus microneutralisation test. Indeed, pseudotyped retroviruses can display the exact Spike protein of the new VOC without the rist of introducing additional unwanted mutations resulting from growing the live virus in tissue culture. During the course of the HICC project a set of pseudotype retroviruses displaying the Spike protein of the following SARS-CoV-2 virses were generated: Wuhan (Ancestral SARSCoV-2), B1.1.7, B.1.351, P1, B1.617.2, B.1617.2, B1.1.529. During the SIREN project, Partnering with Dr Tom Peacock and Prof Wendy Barclay and the G2P consortium, we have been able to generate new pseudotype viruses repsenting the latest VOC, namely: BA1, BA2, BA4/5, BQ.1.1, XBB, BA.2.75.2, BA2.3.20, BA.4.6, BA.2.3.20, BQ.1.1, XBB and XBB1.5. These are being used in this project and will be made avialble for further research aimed at characterising the breadth of the VNAb responses of vaccinated and infected individuals. The pseutotype retroviruses listed above completes 
 
Title Standardisation of virus neutralising antibody levels and antigen-specific binding antibodies to SARSCoV-2 
Description In collaboration with Dr Mark Page, NIBSC (National Institute for Biological Standards and Control), we have adapted all our virus neutralisation assays (VNAb) and antigen-specific binding antibody assays to express the results in International Units (IU) or Binding Antibody Units (BAU) using WHO standard reagents. Thus, measurements of these assays could be transformed from MFI units or IC50 into IU or BAU for VNAb or binding antibody (ELISA, Luminex, Semi-automated Western blotting) assays. We calculated log IC50 values to summarise the RBD-specific and N-specific antibodies as measured by ELISA and neutralising antibody titre as measured by neutralisation. Log IC50 values were estimated by fitting four parameter log-logistic regression dose response curves in the R package drc (see reference from publication). The four parameters of this curve are the minimum response, the maximum response, the log of the dilution halfway between the two (IC50), and the gradient at the IC50. Our models actually estimated the natural log of IC50 values because it improved model convergence and produced normally distributed values for downstream analyses. To ensure IC50 values were comparable, a single gradient, minimum, and maximum value was estimated for dose response curves of all samples. To minimise noise between experimental runs the gradient, minimum, and maximum parameters were estimated based on a random subset of 200 samples and fixed for all other samples. Graphical checks showed that these parameters produced curves that fit the observed data well. We observed that this parameter fixing decreased the variance in estimated log IC50 values for calibrants. Samples and calibrants could be assigned an international unitage based on their potency relative to the international standard NIBSC 20/136 which has been assigned an arbitrary unitage of 1000 IU/ml. Unitage for a sample was expressed as Units of sample=Calibrant units×Sample IC50/Calibrant IC50 In practice, the unitage of calibrants was quantified in international units as shown above and the unitage of samples was calculated based on their potency relative to a calibrant with a known international unitage. The reason for this two-step process is that the international standard was not available until December 2020. To assign international units to the calibrants, these were run in duplicate alongside the international standard and relative potencies and international units were calculated as described above. The assumption of parallel curves was verified by comparing the AIC of models which allowed separate gradients to those which did not. The Spearman's rank correlation coefficient for variables pairs and Mann-Whitney U tests were calculated using R. The standardisaation of antibody titres against SARS-CoV-2 is a continuous process that requires revisions according to the emergence of new variants with different antigenicity. This drives the generation of updated WHO Reference antisera which need to be used for calibration of secondary standards (National) and terciary standards (Calibrants for use in testing laboratories). The new WHO standards for SARSC0V-2 bcame aavbailaable laate 2022 and they are currently being used to express the results of antibody titres in International Units. 
Type Of Material Technology assay or reagent 
Year Produced 2021 
Provided To Others? Yes  
Impact The use of IU and BAU is reecognised by WHO as a critical step to improve comparative analysis of vaccine eefficacy data geeneerated in different laboratories around the world. The use of a common Intrenational unit will accelerate vaccine development. By working alongsid eNIBSC in this endevour we are alignede to the ehighest psisblee standards of quality in SARSCoV2 research and we can provide advisee and leadership in this area of research. More work is needed as the emergence of SARSCoV-2 VOC represents an additinal challenge for international standardisation of antibody measurements but th meethods developed during project represent a solid basis on which to build furthere refinemeents that will have real impact in SARSoV-2 immunology. 
 
Title VIBRANT Participant Clinical History Questionnaire 
Description A questionnaire distributed to participants that collected information on their background, clinical history, vaccination history, COVID-19 infection, and household. It received over 1300 responses. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2022 
Provided To Others? No  
Impact The detailed nature of the questionnaire (8 pages long) enabled a more comprehensive understanding of participant's medical histories and experiences of COVID-19, complimenting the existing SIREN datasets. 
 
Description COG-UK 
Organisation UK Health Security Agency
Country United Kingdom 
Sector Public 
PI Contribution I have contributed CL3 facilities and staff to aim with sample processing early in the pandemic for COG-UK (this was a relatively minor contribution)
Collaborator Contribution COG-UK sequenced many SARS-CoV-2 genomes in the UK
Impact Many - but my contribution was very small hence I am not listing them all.
Start Year 2020
 
Description Increase the capability of SIREN for SARS-CoV-2 virus neutralising antibody testing 
Organisation University of Kent
Country United Kingdom 
Sector Academic/University 
PI Contribution Our team in Cambridge has been conducting the required virus neutralising antibody tests of Vaccine Breakthrough plasma samples in Cambridge laboratory facilities and in the Pseudotype Virus Unit (PVU) of the Faculty of Pharmaacy at the University of Kent. Professor Nigel Temperton, the lead of the PVU, Kent, is a long standing collaborator and a member of the HICC (Humoral Immune Correlaaes of COVID-19) and a collaborator of the Laboratory of Viral Zoonotics at the University of Cambridge. On this occassion, Prof Temperton offered his facilities, additional reaagents and expertise to accelerate and support the testing of the large number of plasma samples of this project. Dr Javier Castillo-Olivares is working at both Cambridge and Kent facilities to rpvide high quality data for the SIREN project. In addition, this interaction will increase the capability of conducting in-depth research on the antigenic variability of SARS-CoV-2 variants. Indeed, the capacity of HICC (including PVU, Kent) to generate a large panel of SARS-CoV-2 Spike pseudotypes is significant and would represent an emergency resource for conducting VNAb tests of samples originating from future outbreaks due to novel VOC
Collaborator Contribution As above.
Impact Outputs: VNAb data for the SIREN project. Papers in preparation. Disciplines: Serology, virology, epidemiology
Start Year 2022
 
Description European Congress of Clinical Microbiology & Infectious Diseases Invitation to Talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk European Congress of Clinical Microbiology & Infectious Diseases - PITCH.
Year(s) Of Engagement Activity 2022
 
Description Further articles in London review of Books on COVID-19 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact https://www.lrb.co.uk/the-paper/v43/n24/rupert-beale/on-omicron
Year(s) Of Engagement Activity 2020,2021
URL https://www.lrb.co.uk/the-paper/v43/n24/rupert-beale/on-omicron
 
Description Investigating cases of vaccine break-through (VBT) infections with Delta SARS-CoV-2 within the SIREN Cohort 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact As part of the G2P Consortium, Imperial College London has investigated cases of vaccine break-through (VBT) infections with Delta SARS-CoV-2 within the SIREN Cohort. The hypothesis is that following a vaccine, individuals may elicit either a general or more focused immune response and that the latter would be less effective at neutralising a virus with a mutated epitope within the Spike protein, resulting in a VBT case. Preliminary data has been generated, and this research has involve colleagues at the Crick Institute and University of Glasgow. Further testing will be carried out to add a single mutant to an established delta VBT pseudovirus neutralisation platform. The mutant will be tested against its matching homologous serum as well as a panel of standardized control sera.
Year(s) Of Engagement Activity 2022,2023
 
Description Invited talk American Society for Nephrology 2022, Orlando 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk American Society for Nephrology 2022, Orlando
Year(s) Of Engagement Activity 2022
 
Description Invited talk Federation of Clinical Immunology Societies 2022, San Francisco 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk Federation of Clinical Immunology Societies 2022, San Francisco (Crick)
Year(s) Of Engagement Activity 2022
 
Description Invited talk Microbiology Society 2022 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited talk Microbiology Society 2022, Belfast
Year(s) Of Engagement Activity 2022
 
Description Keynote speaker European Society for Clinical Virology 2022, Manchester 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Keynote speaker European Society for Clinical Virology 2022, Manchester (CRICK)
Year(s) Of Engagement Activity 2022
 
Description Living with immunodeficiency, living with COVID Webinar. Organised in collaboration with British Socitey of Immunology Immunodeficiency UK UKPIN and the COVAD study 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Webinar in response to national concern from immunodeficiency patients about national policy to remove covid restrictions without a specific plan for this patient group who remain vulnerable due to poor response to vaccination. Collaborating with our key patient organisation, our national professional network UKPIN and the BSI. ~Speakers include patient rep, chair of UKPIN, and co lead in COVAD Professor Burns. We delivered 3 talks around covid through the waves for our patients, vaccine responses and treatment options. There was a 30 minutes Q&A. Questions from this will be taken forward to lobby the government through these partner organisations
Year(s) Of Engagement Activity 2022
URL https://www.immunology.org/events/living-immunodeficiency-living-covid-19
 
Description NHS HRA blog: How public involvement improved our study 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Anna Howells, a Public Health Fellow in the SIREN team at the UKHSA wrote a blog for the NHS Health Research Authority website on the importance of public involvement and how it benefitted the SIREN study. This blog covers information on learnings from SIREN's experience of working with our Participant Involvement Panel to date and how the Panel has helped the research team overcome challenges. The blog was published to coincide with the one year anniversary of the Shared Commitment on Public Involvement and has been publicised through multiple online and social media channels.
Year(s) Of Engagement Activity 2023
URL https://www.hra.nhs.uk/planning-and-improving-research/best-practice/public-involvement/putting-peop...
 
Description Oral presentations at European Congress of Clinical Microbiology & Infectious Diseases 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Abstracts have been selected for presentation at ECCMID 2022 in Lisbon, Portugal April 23rd-26th 2022, the 32nd meeting of this large international infectious diseases conference.
Including:
26/04, 13:30 - 15:30 WET 2-Hour Oral Session
12. COVID-19 vaccine immunogenicity, efficacy and effectiveness
1. Ashley Otter "Determinants of SARS-CoV-2 anti-spike antibody levels following BNT162b2 vaccination: a cross-sectional analysis of 6,000 UK healthcare workers (SIREN study)"
2. Victoria Hall "Effectiveness and durability of protection against future SARS-CoV-2 infection conferred by COVID-19 vaccination and previous infection: findings from the UK SIREN prospective cohort study of healthcare workers March 2020 to September 2021"
3. Susanna Dunachie "Humoral and cellular immunity to SARS-CoV-2 from vaccination and infections: the UK PITCH consortium"
Year(s) Of Engagement Activity 2022
URL https://www.eccmid.org/scientific_programme/2022_programme_live_sync/
 
Description PPI (Patient and Public Involvement) Panel 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact Two phases of the SIREN PIP have been recruited and run. Around 30 participants expressed an interest in joining Phase 1 of the PIP, with this number increasing to 485 for Phase 2. Seven participants were involved in Phase 1 for eight months and ten participants were involved in Phase 2 for six months. Eleven SIREN PIP meetings have taken place, in Phase 1 the average attendance rate across the six meetings was 76%, with an attendance rate of 85% recorded for Phase 2.

Over 15 researchers from the SIREN study team and Consortium organisations have joined meetings to seek insights from the PIP on a broad range of topics. The PIP have been able to share advice around the planning phase of projects as well as inputting into how to best share findings with SIREN participants or the wider public.

The PIP plays a vital role in informing the design of participant and public engagement activities, including written communications such as newsletters and plain language summaries, and joining participant webinars and featuring in SIREN public videos.
Year(s) Of Engagement Activity 2022,2023
 
Description Panel member for British Society of Immunology / UK-CIC public & patient engagement discussion for studies understanding COVID-19 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact I was 3 x a Panel member for British Society of Immunology / UK-CIC public & patient engagement discussion for studies understanding COVID-19. These were targeted at patient representatives with immunocompromise, who sought to understand the impact of various causes of immune compromise on their response to vaccination against COVID-19
Year(s) Of Engagement Activity 2021,2023
URL https://twitter.com/britsocimm/status/1407600541841166337?s=20&t=xmlBl2fVkp2BC_-m5pFePQ
 
Description Participation in a visit from the Minister for Health Maggie Throup to unit to discuss role of SIREN and Consortium in contributing to Policy 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Minister for Health visited site to discuss the research work that SIREN was delivering in order to deliver on policy objectives related to vaccines
Year(s) Of Engagement Activity 2022
 
Description Presentation at the British Society for Immunology Congress on Antibody correlates of protection from SARS-CoV-2 reinfection: a case-control study 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A poster presentation at the British Society for Immunology Congress, as below:

Ana Atti, Ferdinando Insalata, Edward J Carr, Ashley D Otter, Javier Castillo-Olivares, Mary Wu, Ruth Harvey, Michael Howell, Andrew Chan, Jonathan Lyall, Nigel Temperton, Diego Cantoni, Kelly da Costa, Angalee Nadesalingam, Andrew Taylor-Kerr, Nipunadi Hettiarachchi, Caio Tranquillini, Jacqueline Hewson, Michelle J Cole, Sarah Foulkes, Katie Munro, Edward J M Monk, Iain D Milligan, Ezra Linley, Meera A Chand Colin S Brown, Jasmin Islam, Amanda Semper, Andre Charlett, Jonathan L Heeney, Rupert Beale, Maria Zambon, Susan Hopkins, Tim Brooks, Victoria Hall, SIREN Study Group and the Crick COVID Immunity Pipeline Consortium. Antibody correlates of protection from SARS-CoV-2 reinfection: a case-control study. British Society for Immunology Congress - 05-08 December 2022, Liverpool, UK.
Year(s) Of Engagement Activity 2022
 
Description Presentation at the British Society for Immunology on SIREN PIP members past & present 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A poster presentation at the British Society for Immunology, as below:

Erika Aquino, Anna Howells, Jennie Evans, Victoria Hall, Jasmin Islam, SIREN PIP members past & present Embedding participant involvement in the SARS-CoV 2 immunity and reinfection evaluation (SIREN) study. British Society for Immunology, December 2022 Liverpool, UK
Year(s) Of Engagement Activity 2022
 
Description Presentation at the British Society for Immunology on antibody responses following third doses of BNT162b2 mRNA vaccine 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Poster presentation at the British Society for Immunology, as below:

Iain Milligan, Edward Carr, Sarah Foulkes, Ashley Otter, Ross Harris, Ayoub Saei, Jasmin Islam, Amanda Semper, Susan Hopkins, Tim Brooks, Rupert Beale Victoria Hall. Binding and neutralising antibody responses following third doses of BNT162b2 mRNA vaccine in COVID-19 naïve and recovered healthcare workers in the SIREN study. British Society for Immunology, December 2022 Liverpool, UK
Year(s) Of Engagement Activity 2022
 
Description Presentation for the UK Health Security Agency Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact A poster presentation titled 'How do you keep a cohort engaged? Lessons from one year of following up over 44,000 SIREN study participants' was presented at the UK Health Security Agency Conference, October 2022, UK to raise awareness of the Consortium's work engaging the SIREN cohort.
Year(s) Of Engagement Activity 2022
 
Description Presentations at UK Variant Technical Group and Joint Committee of Vaccinations and Immunisations 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The work from SIREN and PItch Plus consortium including the basic science work has been presented to the Variant Technical group and resulting reports and also to JCVI who lead on the recommendations for vaccines to Ministers.
Year(s) Of Engagement Activity 2021,2022
URL https://www.gov.uk/government/publications/investigation-of-sars-cov-2-variants-technical-briefings
 
Description Presentations on SIREN at the European Conference of Clinical Microbiology and Infectious Diseases (ECCMID April 2022 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Seven abstracts on the immune response to vaccination and infection in SIREN and PITCH cohorts were accepted for presentation at the ECCMID conference April 2022 by Ashley Otter, Susannah Dunachie, Victoria Hall, Ana Atti, Sarah Foulkes, Edward Monk and Stephanie Evans. This raises the profile of the SIREN Consortium within the academic community, and shares valuable data with the international scientific community.
Year(s) Of Engagement Activity 2022
URL https://2022.eccmid.org/
 
Description Presentations on SIREN at the European Conference on Applied Infectious Disease Epidemiology (ESCAIDE 2022) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentations on SIREN at ESCAIDE:

Sarah Foulkes. How do we keep a cohort engaged? Lessons from one year of following up over 44,000 SIREN study participants. The European Scientific Conference on Applied Infectious Disease Epidemiology (ESCAIDE) 23-25/11/2022, Stockholm Sweden.

Michelle Cole. Early Warning Surveillance for SARS-CoV-2 Omicron Variants, United Kingdom, November 2021-September 2022. The European Scientific Conference on Applied Infectious Disease Epidemiology. 23-25 November 2022, Stockholm, Sweden.

Edward J M Monk, Diane Pople, Stephanie Evans, Sarah Foulkes, Jasmin Islam, Enemona Adaji, Naomi Platt, Edgar Wellington, Ana Atti, Russell Hope, SIREN Study Group, Julie Robotham, Susan Hopkins, Colin S Brown, Victoria J Hall. Occupational risk factors for SARS-CoV-2 infection amongst healthcare workers in England during the second wave: the SIREN prospective cohort study, September 2020 - April 2021. The European Scientific Conference on Applied Infectious Disease Epidemiology. 23-25 November 2022, Stockholm, Sweden.

Victoria Hall, Ferdinando Insalata, Sarah Foulkes et al. Effectiveness of BNT162b2 mRNA booster doses and hybrid-immunity in protecting against SARS-CoV-2 infections during the Delta and Omicron variant waves; the UK SIREN study September 2021 to February 2022. The European Scientific Conference on Applied Infectious Disease Epidemiology. 23-25 November 2022, Stockholm, Sweden.
Year(s) Of Engagement Activity 2022
URL https://www.escaide.eu/en/escaide-programme-2023
 
Description Rapid analysis of protection from vaccination and prior infection in SIREN cohort during Omicron variant period 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Rapid analysis of protection from vaccination and prior infection in SIREN cohort during Omicron variant period published in UKHSA Variant Technical Briefings and comprehensive analysis for peer reviewed publication in final stages (Preprint/submission May 2022)
Year(s) Of Engagement Activity 2022
 
Description Research Paper on the Participant Engagement Panel due to be submitted 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A research paper centred on the SIREN Consortium's Participant Involvement Panel has been drafted, titled: 'Demonstrating the learning and impact of embedding participant involvement in a pandemic research study: The experience of the SARS-CoV-2 Immunity & Reinfection Evaluation (SIREN) study UK, 2020-2023'.

it is due to be submitted for publication shortly.
Year(s) Of Engagement Activity 2023
 
Description SIREN Consortium Featured in National Core Studies Immunity COVID-19 Report 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact A report by the National Core Studies Immunity, titled 'Patient and public involvement in COVID-19 research: bridging the gap between theory and practice' featured a section on VIBRANT, which discussed the SIREN Consortium's work, including the Participant Involvement Panel. It included quotes from participants involved in the Panel, and from Alex Richter outlining how valuable the Panel has been for the SIREN Consortium.
Year(s) Of Engagement Activity 2022
URL https://www.covidvaccineresearch.org/sites/default/files/2022-12/NCSI%20PPI%20Report.pdf
 
Description SIREN Consortium Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact A SIREN Consortium Workshop was held in October 2022 at Nobel House, Westminster, to discuss the Consortium's research to-date, and promising avenues for future research that had been identified with the group.
Year(s) Of Engagement Activity 2022
 
Description SIREN Participant webinars 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact The SIREN team run regular online participant webinars, as part of the evolving cohort retention programme. These provide updates on study development and latest research outputs from SIREN and the SIREN Consortium, presented in an inclusive format. The events include live participant Q&A sessions so participants can ask questions directly from the study team. Events are recorded and circulated to those unable to attend in person, and digests are shared via email.
Year(s) Of Engagement Activity 2021,2022,2023
 
Description SIREN Webpage on the Government Website 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The UK Government added a page on SIREN to its COVID-19 information, which includes a section on the SIREN Consortium.

The aim was to raise awareness of SIREN and the Consortium's research to the general public. The webpage contains information on the Consortium partners and research funding.
Year(s) Of Engagement Activity 2022
URL https://www.gov.uk/guidance/siren-study
 
Description SIREN asked to present at the National Core Studies Immunity (NCSi) Patient and Public Involvement (PPI) training course 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact UKHSA SIREN researchers were asked to present at the NCSi PPI course taking place in March 2023, to share learning from the SIREN experience of setting up, recruiting and running a Participant Involvement Panel (PIP). The SIREN PIP is run in partnership with the British Society for Immunology (BSI). Attendees at the NCSi PPI course are other researchers looking to implement PPI in their own studies or practice.
Year(s) Of Engagement Activity 2023
 
Description SIREN study video series 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact The SIREN team designed and developed a series of three videos to showcase the study, highlight its story and demonstrate the valuable role of research teams and participants within the study. The first video in the series was premiered in a participant-wide webinar in July 2022, with the video series subsequently shared via NHS site and participant newsletters, before being uploaded onto the gov.uk SIREN study webpage. The videos have led to increased engagement with sites and participants, including requests from site teams to share the video at events taking place at their organisations.
Year(s) Of Engagement Activity 2022
URL https://www.gov.uk/guidance/siren-study
 
Description Scientific advisor for resources to explain COVID-19 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact I worked with the media office of the British Society for Immunology to create visual tools to explain vaccination and immunity to SARS-CoV-2 to a general lay audience
Year(s) Of Engagement Activity 2021
URL https://www.immunology.org/coronavirus/connect-coronavirus-public-engagement-resources/covid-immunit...
 
Description UK Clinical Immunology Consortium Invitations 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited talk UK Clinical Immunology Consortium by two different members.
Year(s) Of Engagement Activity 2022
 
Description UK Covid Vaccine Research Hub blog celebrating the SIREN study and consortium 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The SIREN study were asked to write a blog to be published on the UK Vaccine Research Hub, a national network to share news about COVID-19 funded by UK Research and Innovation (UKRI). The blog was shared on social media (Twitter) and highlighted in SIREN study newsletters sent out to NHS site teams and participants.
Year(s) Of Engagement Activity 2022
URL https://www.covidvaccineresearch.org/news/siren-study-and-consortium-strength-strength
 
Description UK Government Blog on the SIREN Consortium 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact A blog on the government website, credited to the UK Health Security Agency and Public Health England, announced the grant award to the SIREN Consortium, and outlined their key activities and research partnerships.
Year(s) Of Engagement Activity 2021
URL https://www.gov.uk/government/news/ukhsa-launches-study-to-better-understand-covid-19-vaccine-respon...
 
Description UK Health Security Agency UK COVID-19 surveillance Data Debrief Group 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact National group of expert scientists and policymakers meeting weekly to review latest COVID-19 data to advise Secretary of State. SIREN data on PCR positivity, reinfections and variants presented fortnightly by Sarah Foulkes and Victoria Hall
Year(s) Of Engagement Activity 2021,2022,2023
 
Description Visit from shadow health secretary 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Visit from shadow health minister and local MP to hear about the COVID work that had been undertaken in Birmingham. Presented COVAD and highlighted the difficulties for immunodeficiency patients who remain vulnerable to feed into the labour strategy of living with COVID. The Local MP tabled a question in parliament to raise this issue in response to the visit.
Year(s) Of Engagement Activity 2022