Protective and Dysfunctional Antiviral Immunity
We focus on viruses that are major global health challenges. As part of this, we analyse how innate and adaptive immune responses differ in people with efficient versus poor virus control.
Our Work
Haemodialysis on response to vaccination and infection
Dr Douglas Fink has received a start-up grant to investigate why response to vaccination and infection is reduced in patients receiving haemodialysis.
The immune system has the capacity to mount protective immunity to acute and chronic virus infections but when such responses fail, they can instead contribute to the resulting disease pathology. Careful dissection of the molecular basis of protective and harmful immunity using human samples, in addition to appropriate model systems, is essential to tailor novel therapies.
We research both innate and adaptive immune responses, analysing how these differ in those with efficient versus poor virus control. We take advantage of our close links with the Royal Free London to access tissue samples, allowing us to study organ-specific immunity at the sites of infection.
Projects
We have identified an association between memory T cells targeting the conserved replication-transcription complex of SARS-CoV-2 and early viral control without seroconversion (ie abortive infection). We are now characterising these T cells to identify which qualities and specificities confer protection.
Lead Investigators
- Dr Leo Swadling (Institute of Immunity & Transplantation, UCL)
- Professor Mala Maini (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Mahdad Noursadeghi (Infection, UCL)
- Professor Antonio Bertoletti (Duke-NUS, Singapore)
Funding
- Rosetrees Trust & Pears Foundation – Advancement Fellowship
- MRC Consortium funding
We identified tissue-resident T cells in pre-pandemic human airway samples able to cross-recognise SARS-CoV-2, optimally situated to abort infection through frontline immune surveillance. We are examining persistence of these sentinel mucosal responses following SARS-CoV-2 infection and/or vaccination in UK and Malawi cohorts +/- HIV infection. We will investigate whether airway T and B cells have superior potential for transmission-blocking pan-coronavirus reactivity through enhanced cross-reactivity +/- more rapid/potent antiviral function.
Lead Investigator
- Professor Mala Maini (Institute of Immunity & Transplantation, UCL)
Network Collaborators
- Dr Elena Mitsi (University of Oxford)
- Dr Daniela Ferreira (University of Oxford)
- Dr Kondwani Jambo (Liverpool School of Tropical Medicine and Malawi)
Collaborators
- Professor Tao Dong (University of Oxford)
- Professor Elma Tchilian (Pirbright Institute)
- Dr Laura McCoy (Institute of Immunity & Transplantation, UCL)
Funding
- Wellcome Covid-19 Variants Network award
- Wellcome Investigator award
We are characterising adaptations of ‘gold-standard’ HBV-specific and global liver-resident T cells surviving and maintaining control in naturally resolved infection and testing immunotherapeutic strategies to recapitulate their functional hallmarks.
Lead Investigator
- Professor Mala Maini (Institute of Immunity & Transplantation, UCL)
Collaborators
- Dr Leo Swadling (Institute of Immunity & Transplantation, UCL)
- Prof Muzlifah Haniffa (University of Newcastle and Sanger Institute)
- Professor Xavier Forns (Hospital Clínic de Barcelona)
- Liver surgical team and Tissue Access for Patient Benefit (Royal Free Hospital)
Funding
- Wellcome Investigator award
We are identifying protective TCR sequences from the site of hepatitis-B virus (HBV) infection, the liver, to increase our understanding of immune regulation of this virus and to develop next generation TCR gene therapies.
Lead Investigator
- Dr Leo Swadling (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Xavier Forns (Hospital Clínic de Barcelona)
- Professor Mala Maini (Institute of Immunity & Transplantation, UCL)
Funding
- Medical Research Foundation
We are investigating whether alterations in B cell phenotypes explain why only rare individuals are able to make broadly neutralising antibodies against HIV. We are particularly interested in how B cell activation differences are related to antibody affinities.
Lead Investigator
- Dr Laura McCoy (Institute of Immunity & Transplantation, UCL)
Collaborators
- Dr Marit van Gils (University of Amsterdam)
- Professor Aine McKnight (Queen Mary, University of London)
- Professor Ravindra Gupta (University of Cambridge)
- Professor Rachel McKendry (London Nanotechnology Centre)
- Professor Peter Cherepanov (The Francis Crick Institute, London)
- Professor Menna Clatworthy (University of Cambridge)
Funding
- European Research Council
We are investigating how HIV-1 latency is established or reversed. We study how the three-dimensional organization of chromatin in lymphocytes affects the establishment of HIV-1 latency and how HIV-1 gene expression is controlled in specific T helper cell subtypes.
Lead Investigator
- Professor Ariberto Fassati (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Eric Schirmer (Institute of Cell Biology, University of Edinburgh)
- Professor Petronela Ancuta (CHUM, University of Montreal, Canada).
Funding
- Medical Research Council
- Canadian Institute of Health Research
- Government of Oman
- Government of Saudi Arabia
We are dissecting the host and viral mechanisms responsible for controlling latency and reactivation of human cytomegalovirus (HCMV) - a pathogen important for disease in transplant patient populations. Key questions include defining the molecular determinants that regulate viral infection, alongside understanding the immunological basis for control in healthy people. We aim to harness this knowledge to develop strategies to protect our immune-suppressed transplant patients.
Lead Investigator
- Dr Matthew Reeves (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Judy Breuer (Institute of Child Health, UCL)
- Professor Reza Motallabzadeh (Institute of Immunity & Transplantation, UCL)
- Dr. Mark Harber (Royal Free Hospital, UCL)
- Professor Mark Wills (University of Cambridge)
- Professor Richard Stanton (University of Cardiff)
Funding
- Medical Research Council
- Wellcome Trust
- BBSRC
- Royal Free Charity
- Qatari Government (Defence Attache)
Human cytomegalovirus (HCMV) replicates in tissue to cause disease. Understanding the role of tissue resident immunity for the control of viral replication is important for the design of future immunological interventions. We have recently identified that differences in donor-derived immune responses within the transplant organ are a potential correlate of outcome post-transplant in the recipient. The goal now is to understand the role of individual immune functions and why they are protective when enriched for in the transplanted organ.
Lead Investigator
- Dr Matthew Reeves (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Reza Motallabzadeh (Institute of Immunity & Transplantation, UCL)
- Dr Victoria Male (Imperial College London)
- Professor Mark Wills (University of Cambridge)
Funding
- Medical Research Council
- Kidney Research UK
- Rosetrees
BK polyoma virus (BKpV) is a major cause of disease in renal transplant patients. Relieving immune suppression is the only mechanism of viral control but leads to graft rejection. We are currently using samples from our patient cohorts to identify immunological correlates of protection with a specific focus on broadly neutralising antibody responses that protect from infection with multiple BKpV genotypes.
Lead Investigator
- Dr Matthew Reeves (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Alan Salama, Department of Renal Medicine, UCL)
- Dr Stephanie Chong (Department of Renal Medicine, UCL)
- Professor Reza Motallabzadeh (Institute of Immunity & Transplantation, UCL)
- Dr Laura McCoy (Institute of Immunity & Transplantation, UCL)
Funding
- Kidney Research UK
- Rosetrees
- Royal Free Charity
- St Peter's Trust
This project aims to identify the innate immune mechanisms involved in the initial response to HIV infection, including identification of NK cell subsets with adaptive/‘memory’ features that can be induced by novel vaccination strategies.
Lead Investigator
- Dr Dimitra Peppa (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Sarah Rowland Jones (University of Oxford)
- Professor Eduard Sanders (Kilifi, Kenya)
Funding
- BHIVA
- Saudi Ministry of Education Prize scholar (D.Phil. Student)
Type 1 interferon (T1IFN) signalling is critical in immune responses to viruses. Auto-antibodies (Abs) that bind and neutralise T1IFN are strongly associated with poor outcomes during SARS-CoV-2, influenza and West Nile Virus disease. We will measure the full spectrum anti-IFN auto-Abs (across T1IFN, T2IFN and T3IFN sub-types) in people living with chronic virus infection, including HIV and chronic hepatitis B virus, and characterise associations with key virological and clinical outcomes.
Lead Investigator
- Dr Douglas Fink (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Mala Maini (Institute of Immunity & Transplantation, UCL)
- Dr Laura McCoy (Institute of Immunity & Transplantation, UCL)
- Dr Dimitra Peppa (Institute of Immunity & Transplantation, UCL)
- Dr Upkar Gil (Queen Mary, University of London)
Funding
- British HIV Association
- UCL Therapeutic Acceleration Support Fund
Coronaviruses typically infect people through cells lining their nose, throat and lungs. Mucosal immunity generated at these surfaces is highly specialised and very different to immune responses in the circulation. Boosting mucosal immunity could be the key to developing vaccines that can block viruses from being able to spread from one person to another. The five-year Mucosal Immunity in human Coronavirus Challenge (MusiCC) project will be led by Imperial College London and involve collaborators across the UK, Europe, Singapore and USA. The consortium will develop human challenge models for coronavirus trials and mechanistic studies of mucosal immunity. The trials will test potential mucosal vaccine candidates against beta-coronaviruses. UCL and the Royal Free Hospital will deliver clinical and laboratory work packages within the consortium.
Chief Investigator
- Professor Christopher Chiu (Imperial College London)
Principal Investigator
- Dr Douglas Fink (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Rob Heyderman (UCL)
- Professor Mahdad Noursadeghi (UCL)
- Professor Helen McShane (University of Oxford)
Funding
- Coalition for Epidemic Preparedness Innovations (CEPI)
- Horizon Europe
The circadian clock is a crucial regulator of immunity, influencing how the body defends against pathogens. Our research aims to understand how the circadian system regulates immune responses to viral infections, with a specific focus on the hepatitis B virus. This will allow us to optimise the time-of-day for vaccine administration to improve efficacy. Additionally, our work involves characterising the communication between immune cells and the liver stroma in the context of the circadian clock and investigating how infections may alter this communication.
Lead Investigator
- Dr Alan Xiaodong Zhuang (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Russell Foster (University of Oxford)
- Professor Mala Maini (Institute of Immunity & Transplantation, UCL)
Funding
- Medical Research Council
Our Experts
Pears & Rosetrees Fellow
Viral Immunity
Associate Professor
Cellular & Molecular Virology
Associate Professor
HIV Immunology
Principal Clinical Fellow
Infection & Immunity
Are Some People 'Super-Immune' to Covid?
At least some people who have avoided Covid are beyond lucky - they appear to have a sort of 'super immunity'. Dr Leo Swadling speaks to Bloomberg.
Funding and Partnerships
Selected Publications
- Sun B, da Costa KAS, Alrubayyi A ... Maini MK, Bashford-Rogers R, Gill US, Peppa D (2024). HIV/HBV coinfection remodels the immune landscape and natural killer cell ADCC functional responses. Hepatology. 2024 Sep 1;80(3): 649-663.
- Fink DL, Idilli O, Shields A, et al (2024). Prevalence of Anti-Interferon α Auto-Antibodies in Patients with Antibody Deficiency. J Clin Immunol. 2024 Jul 11;44(7): 161.
- Thomas P, Rees-Spear C, Griffith S ... McCoy LE (2024). High affinity mAb infusion can enhance maximum affinity maturation during HIV Env immunization. iScience. 2024 Mar 11;27(4): 109495.
- Moreno-Cubero E, Alrubayyi A, Balint S ... Peppa D (2024). IL-15 reprogramming compensates for NK cell mitochondrial dysfunction in HIV-1 infection. JCI Insight. 2024 Jan 16;9(4): e173099.
- Murray MJ, Bradley E, Ng Y ... Reeves MB (2023). In silico interrogation of the miRNAome of infected hematopoietic cells to predict processes important for human cytomegalovirus latent infection. J Biol Chem. 2023 Jun;299(6): 104727.
- Borrmann H, Ulkar G, Kliszczak AE ... Zhuang X, McKeating JA (2023). Molecular components of the circadian clock regulate HIV-1 replication. iScience. 2023 May 29;26(7): 107007.
- Forrest C, Chase TJG, Cuff AO ... Reeves M (2023). Control of human cytomegalovirus replication by liver resident natural killer cells. Nat Commun. 2023 Mar 14;14(1): 1409.
- Touizer E, Alrubayyi A, Ford R ... Peppa D, McCoy LE (2023). Attenuated humoral responses in HIV after SARS-CoV-2 vaccination linked to B cell defects and altered immune profiles. iScience. 2023 Jan 20;26(1): 105862.
- Fink DL, Callaby H, Luintel A, et al (2023). Clinical features and management of individuals admitted to hospital with monkeypox and associated complications across the UK: a retrospective cohort study. Lancet Infect Dis. 2023 May;23(5): 589-597.
- Alrubayyi A, Moreno-Cubero E, Hameiri-Bowen D ... Peppa D (2022). Functional Restoration of Exhausted CD8 T Cells in Chronic HIV-1 Infection by Targeting Mitochondrial Dysfunction. Front Immunol. 2022 Jul 5;13: 908697.
- Diniz MO, Schurich A, Chinnakannan SK ... Maini MK (2022). NK cells limit therapeutic vaccine-induced CD8+T cell immunity in a PD-L1-dependent manner. Sci Transl Med. 2022 Apr 13;14(640): eabi4670.
- Wiche Salinas TR, Zhang Y, Sarnello D ... Fassati A (2021). Th17 cell master transcription factor RORC2 regulates HIV-1 gene expression and viral outgrowth. Proc Natl Acad Sci USA. 2021 Nov 30;118(48): e2105927118.
- Zhuang X, Tsukuda S, Wrensch F, et al (2021). The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells. iScience. 2021 Oct 22;24(10): 103144.
- Rees-Spear C, Muir L, Griffith SA ... McCoy LE (2021). The effect of spike mutations on SARS-CoV-2 neutralization. Cell Rep. 2021 Mar 23;34(12): 108890.
- Zhuang X, Forde D, Tsukuda S, et al (2021). Circadian control of hepatitis B virus replication. Nat Commun. 2021 Mar 12;12(1): 1658.
- Swadling L, Pallett LJ, Diniz MO ... Maini MK (2020). Human Liver Memory CD8+ T Cells Use Autophagy for Tissue Residence. Cell Rep. 2020 Jan 21;30(3): 687-698.e6.
- Monit C, Morris ER, Ruis C ... Fassati A, Goldstein RA (2019). Positive selection in dNTPase SAMHD1 throughout mammalian evolution. Proc Natl Acad Sci USA. 2019 Sep 10;116(37): 18647-18654.
- Dupont L, Du L, Poulter M, Choi S, McIntosh M, Reeves MB (2019). Src family kinase activity drives cytomegalovirus reactivation by recruiting MOZ histone acetyltransferase activity to the viral promoter. J Biol Chem. 2019 Aug 30;294(35): 12901-12910.
- Burton AR, Pallett LJ, McCoy LE, Suveizdyte K, Amin OE, Swadling L ... Maini MK (2018). Circulating and intrahepatic antiviral B cells are defective in hepatitis B. J Clin Invest. 2018 Oct 1;128(10): 4588-4603.
- Zhyvoloup A, Melamed A, Anderson I ... Fassati A (2017). Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation. PLoS Pathog. 2017 Jul 20;13(7): e1006460.
Novel CMV vaccine prevents cell-to-cell spread
In a post-pandemic world, governments around the world are looking to get ahead of the next threat to public health. However, to outsiders, the pace of vaccine development compared to the COVID-19 vaccine could seem slow. One of the herpes family of viruses, CMV, has likely infected billions of people just since the 1970s. Dr Matthew Reeves discusses his input to CMV management, vaccine research, and virology as a whole.
New immunotherapy 'highly effective' against hep B virus
UCL scientists have identified a new immunotherapy to combat the hepatitis B virus (HBV), the most common cause of liver cancer in the world.
