Antiviral Vaccines and Therapies
We focus on translating our research findings into novel approaches to prophylactic vaccination (e.g. against coronavirus) and therapeutic vaccination (and hepatitis B virus).
Novel CMV vaccine prevents cell-to-cell spread
Dr Matthew Reeves discusses his input to the management of CMV (one of the herps family of viruses), vaccine research, and virology as a whole.
Our work
At the IIT, we have a strong focus on translating our research findings into novel approaches to prophylactic and therapeutic vaccination, for example against coronaviruses and hepatitis B virus, respectively.
We also prioritise researching the particular issues associated with harnessing effective immunity in populations with inherited or acquired immunodeficiency, including HIV.
By studying the suboptimal responses of these populations to existing antivirals and vaccines, we aim to identify those most at risk and tailor next generation therapeutics suitable to overcome immunodeficiencies.
Projects
Informed by our earlier work on T cell correlates of protection, we are now investigating whether a vaccine containing early expressed and conserved coronavirus antigens, targeted to the respiratory mucosa, will provide pan-coronavirus protection.
Lead Investigators
- Dr Leo Swadling (Institute of Immunity & Transplantation, UCL)
- Professor Mala Maini (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Ellie Barnes (University of Oxford)
- Professor Matteo Iannacone (San Raffaele Scientific Institute, Milan)
Funding
- MRC - Therapeutic accelerator scheme
We are studying the impact of intravenous sotrovimab for COVID-19 in immunosuppressed patients, in terms of viral persistence, viral mutation (especially those associated with sotrovimab resistance) and clinical outcomes. This study (LUNAR) is funded and sponsored by GlaxoSmithKline with viral sequencing done at UCL.
Lead Investigators
- Dr David Lowe (Institute of Immunity & Transplantation, UCL)
- Professor Judy Breuer (Institute of Child Health, UCL)
Funding
- GlaxoSmithKline
We are running a sub-study of the national Platform Adaptive trial of for eArly NOvel antiviRals treatMent of COVID-19 in the Community (PANORAMIC) study. The trial is investigating early oral treatments for COVID-19 in high-risk patients and the UCL sub-study investigates the impact of the drugs on viral load, viral mutation, host inflammatory response and host immune response (anti-SARS-CoV-2 spike antibody).
Lead Investigators
- Dr David Lowe (Institute of Immunity & Transplantation, UCL)
- Professor Judy Breuer (Institute of Child Health, UCL)
- Professor Joe Standing (Institute of Child Health, UCL)
Collaborators
- Professor Chris Butler (University of Oxford)
- Dr Ly-Mee Yu (University of Oxford)
- Professor Alex Richter (University of Birmingham)
- Dr Adrian Shields (University of Birmingham)
- Dr Theo Sanderson (The Francis Crick Institute, London)
Funding
- National Institute for Health and Care Research (NIHR)
As part of the nationwide PACE study, we have explored immune responses to COVID-19 vaccination in patients with acute myeloid leukaemia (AML) and are now analysing samples to understand serious infection in AML and whether it can be predicted. We are exploring the host transcriptome, microbial DNA in blood and the microbiome in several sample types.
Lead Investigator
- Dr David Lowe (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Tim McHugh (Clinical Microbiology, UCL)
- Dr Sylvia Rofael (Division of Infection & Immunity, UCL)
- Professor Simon Stanworth (University of Oxford)
- Dr Justin Loke (University of Birmingham)
Funding
- Blood Cancer UK
- Bristol Myers Squibb
We are investigating the fundamental rules that underpin T cell cross-reactivity and how vaccines can be rationally designed to induce the most cross-protective immunity. We are studying viral sequence evolution and TCR characteristics to identify cross-reactive epitopes for inclusion in vaccines.
Lead Investigator
- Dr Leo Swadling (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Mala Maini (Institute of Immunity & Transplantation, UCL)
- Dr Lucy van Dorp (UCL Genetics)
- Dr Andreas Mayer (Institute of Immunity & Transplantation, UCL)
We are exploring the role of antibody competition in B cell repertoire development to viral infection. We are also investigating why vaccines fail in immunocompromised populations and how HIV infection alters vaccine responses to coronaviruses, influenza and monkey pox virus.
Lead Investigator
- Dr Laura McCoy (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Ravindra Gupta (University of Cambridge)
- Professor Menna Clatworthy (University of Cambridge)
- Professor Emma Morris (Institute of Immunity & Transplantation, UCL)
- Dr Fiona Burns (Royal Free Hospital / Dept of Population Health, UCL)
- Professor Richard Gilson (Dept of Population Health, UCL)
Funding
- Medical Research Council
- European Research Council
We are leading the antiviral B cell immune monitoring (and contributing to the T cell monitoring) for a multicentre ERC Horizon 2020-funded Phase I/II trial to test a novel immunotherapeutic prime/boost vaccine strategy (TherVacB) for HBV functional cure.
Lead Investigator
- Professor Mala Maini (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Percy Knolle (Technical University of Munich)
- Professor Ulrike Protzer (Technical University of Munich)
- Dr Sabela Lens (FCRB, Barcelona)
- Professor Carlo Ferrari (University of Parma)
Funding
- ERC Horizon 2020
We have uncovered novel paradigms of organ-specific regulation of T cells, for example by liver-resident NK cells and immunosuppressive neutrophils, and are defining molecular pathways to interrupt these in order to enhance immunogenicity of therapeutic vaccines in chronic viral infections like HBV.
Lead Investigators
- Professor Mala Maini (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Eleanor Barnes (University of Oxford)
- Professor Ulrike Protzer (Technical University of Munich)
Funding
- Wellcome Investigator Award
We are interrogating samples collected from a previous phase II trial of a HCMV vaccine performed at the Royal Free Hospital. This approach has identified mechanistic correlates of protection that are being used to inform the design of new vaccines better able to control HCMV infection and disease. This work exploits novel nucleic acid nanotechnology to enhance vaccine design against multiple pathogens.
Lead investigators
- Dr Matthew Reeves (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Paul Griffiths (Emeritus UCL)
- Professor Ben Seddon (Institute of Immunity & Transplantation, UCL)
- Professor Stefan Howorka (Department of Chemistry, UCL)
- Professor Mark Wills (University of Cambridge)
Funding
- Rosetrees Trust
- BBSRC
- Wellcome Trust
- Medical Research Council
- Kidney Research UK
Our primary focus is to gain a comprehensive understanding of immune responses in individuals with chronic HBV and HIV/HBV coinfection, with special emphasis on Natural Killer (NK) cells. By delving into the adaptive-like attributes of NK cells within different anatomical compartments, we aim to unveil new insights into their functionality. Our ultimate objective is to pave the way for the development of cutting-edge NK cell-based immunotherapies tailored for patients with chronic viral diseases.
Lead Investigator
- Dimitra Peppa (Institute of Immunity & Transplantation, UCL)
Collaborators
- Prof. Mala Maini (Institute of Immunity & Transplantation, UCL)
- Dr Upkar Gill (Barts Liver Centre, Barts & The London School of Medicine & Dentistry, QMUL)
- Prof. Karl-Johan Malmberg (Oslo University Hospital)
- Dr Rachael Bashford-Rogers (Department of Biochemistry, University of Oxford, UK)
Funding
- NIH / NIAID
We aim to determine the molecular and cellular mechanisms governing NK cell antiviral function in HIV infection. Based on our recent findings highlighting NK cells modulation of humoral responses, an important aim is to identify key pathways and receptor-ligand interactions that mediate NK cell immunoregulation of the HIV antibody response. This will be instrumental in designing future vaccine strategies that target these pathways, ultimately enhancing the generation of broadly neutralising antibodies.
Lead Investigators
- Dr Dimitra Peppa (Institute of Immunity & Transplantation, UCL)
Collaborators
- Dr Todd Bradley (University of Missouri-Kansas City School of Medicine)
- Professor Persephone Borrow (University of Oxford)
- Professor Bart Haynes (Duke University School of Medicine, USA)
Funding
- NIH / NIAID
Our aim is to dissect the involvement of T cells and NK cell memory responses following SARS-CoV2 natural infection/vaccination, particularly in individuals with suboptimal humoral immunity. By gaining a deeper insight into the factors that offer protection, we can enhance our understanding of vaccine efficacy. This knowledge will guide the development of novel vaccine strategies and enable better monitoring of vulnerable patient populations.
Lead Investigator
- Dr Dimitra Peppa (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Fiona Burns (Royal Free Hospital / Dept of Population Health, UCL)
- Dr Laura Waters (Mortimer Market Centre)
- Mortimer Market Centre, CNWL Research team for Jenner II study
- Ian Charleson Day Centre, Royal Free Hospital, Research team for Jenner II study
Funding
- Roche
The primary objective of this project is to assess the interplay between CMV burden, ongoing inflammation and immune cell dysregulation in people living with HIV. Our goal is to identify patients who would derive significant advantages from CMV prophylaxis and targeted immunotherapies, aiming to reduce the potential emergence of adverse clinical outcomes in the future.
A Pilot, Randomized, Open-Label, Non-Active Comparator Controlled Clinical Trial to Evaluate the Effects of Letermovir Prophylaxis on T-cell Immune Activation in Participants with Treated HIV-1 Infection (PROACTIV TRIAL)
This is an investigator-led randomised open label study, with parallel blood and gut tissue sampling in people living with HIV. It is designed to study the adjunctive use of Letermovir with antiretroviral therapy in reducing immune cell activation by preventing CMV reactivation, investigating its potential to attenuate chronic inflammation.
Lead Investigator
- Dr Dimitra Peppa (Institute of Immunity & Transplantation, UCL)
Collaborators
- Professor Margaret Johnson (ICDC, RFH and UCL)
- Dr Mike Youle (ICDC, RFH)
Funding
- MSD
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.
Our Experts
Hon. Clinical Associate Professor
Viral Immunology
Associate Professor
HIV Immunology
Pears & Rosetrees Advanced Fellow
Funding and Partnerships
Selected Publications
- Cankat S, Demael MU, Swadling L (2024). In search of a pan-coronavirus vaccine: next-generation vaccine design and immune mechanisms. Cell Mol Immunol. 2024 Feb;21(2): 103-118.
- Standing JF, Buggiotti L, Guerra-Assuncao JA … Lowe DM, Breuer J; PANORAMIC Virology Group (2024). Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients. Nat Commun 2024;15(1): 1652.
- Swadling L, Maini MK (2023). Can T Cells Abort SARS-CoV-2 and Other Viral Infections? Int J Mol Sci. 2023 Feb 22;24(5): 4371.
- Alrubayyi A, Touizer E, Hameiri-Bowen D ... McCoy LE, Peppa D (2023). Natural killer cell responses during SARS-CoV-2 infection and vaccination in people living with HIV-1. Sci Rep. 2023;13(1): 18994.
- Gomes AC, Baraniak IA, Lankina A, Moulder Z ... Reeves MB (2023). The cytomegalovirus gB/MF59 vaccine candidate induces antibodies against an antigenic domain controlling cell-to-cell spread. Nat Commun. 2023 Feb 23;14(1): 1041.
- Swadling L, Diniz MO ... McCoy LE, Valdes AM ... Maini MK (2022). Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2. Nature. 2022 Jan;601(7891): 110-117.
- Diniz MO, Mitsi E, Swadling L ... Maini MK (2022). Airway-resident T cells from unexposed individuals cross-recognize SARS-CoV-2. Nat Immunol. 2022 Sep;23(9): 1324-1329.
- Lowe DM, Brown LK, Chowdhury K, et al. (2022). Favipiravir, lopinavir-ritonavir, or combination therapy (FLARE): A randomised, double-blind, 2 × 2 factorial placebo-controlled trial of early antiviral therapy in COVID-19. PLoS Med. 2022 Oct 19;19(10): e1004120.
- Jeffery-Smith A, Burton AR, Lens S ... McCoy LE, Maini MK (2022). SARS-CoV-2-specific memory B cells can persist in the elderly who have lost detectable neutralizing antibodies. J Clin Invest. 2022 Jan 18;132(2): e152042.
- Brown LK, Moran E, Goodman A ... Lowe DM (2022). Treatment of chronic or relapsing COVID-19 in immunodeficiency. J Allergy Clin Immunol. 2022 Feb;149(2): 557-561.e1.
- Alrubayyi A, Gea-Mallorquí E, Touizer E ... McCoy LE, Peppa D (2021). Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV. Nat Commun. 2021 Oct 5;12(1): 5839.
- Capone S, Brown A, Hartnell F ... Swadling L (2020). Optimising T cell (re)boosting strategies for adenoviral and modified vaccinia Ankara vaccine regimens in humans. NPJ Vaccines. Oct 12;5:94.
- 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.
- Baraniak I, Gomes AC, Sodi I ... Reeves MB (2019). Seronegative patients vaccinated with cytomegalovirus gB-MF59 vaccine have evidence of neutralising antibody responses against gB early post-transplantation. EBioMedicine. 2019 Dec;50: 45-54.
- Baraniak I, Kropff B, Ambrose L ... Reeves MB (2018). Protection from cytomegalovirus viremia following glycoprotein B vaccination is not dependent on neutralizing antibodies. Proc Natl Acad Sci U S A. 2018 Jun 12;115(24): 6273-6278.
- Bradley T, Peppa D, Pedroza-Pacheco I, Li D, et al (2018). RAB11FIP5 Expression and Altered Natural Killer Cell Function Are Associated with Induction of HIV Broadly Neutralizing Antibody Responses. Cell. 2018 Oct 4;175(2): 387-399.e17.
Pre-existing polymerase-sp T cells expand in abortive sero-ve SARS-CoV-2 infection
Dr Leo Swadling works on identifying T cell correlates of protection by applying emerging technologies and bioinformatics to the characterisation of T cells at the extremes of controlled or uncontrolled viral infection and post-vaccination. He is probing the link between specificity and function of liver-resident memory T-cells in resolved HBV infection and investigating T cell correlates of protection in abortive versus seropositive SARS-CoV-2 infection.
