Dr Carly Bliss

Publication

• Date
• Type

Research

Adenoviral Vector Development

Adenoviruses (Ad) can be used as vaccine vectors, whereby a transgene is selected based on a specific antigen from a pathogen of interest. Following inoculation with the Ad vectored vaccine, the transgene is expressed at a high level, leading to the generation of potent immune responses against the encoded antigen. Pre-existing immunity to human Ad can hinder this type of vaccine platform, and is a therefore a key consideration when developing viral vectored vaccines. My research explores the use of rare species Ads and chimeric Ads to induce potent immune responses against the vaccine antigen whilst circumventing pre-existing immunity against the vaccine vector. Rare species Ads have low seroprevalence in the human population, while adenoviral chimeras aim to avoid pre-existing immunity via modifications to immunodominant capsid proteins. These two approaches underpin my novel vaccine research into cancer and respiratory pathogens.

Cancer Immunotherapy

Immune responses against viral antigens are maintained at the population level through vaccination and natural infection. Through combining antiviral T cells with selective delivery of viral antigens to tumours, cellular immunity is harnessed as a cancer immunotherapy. This research combines with pre-clinical development of antiviral vaccines, in addition to direct cancer targeting vaccines using adenviral vectors. 

Universal SARS-CoV-2 Vaccines

Using lessons learned in the universal influenza virus vaccine field, I am developing vaccines against SARS-CoV-2 (the causative virus of COVID-19) to induce immune responses that are reactive against multiple variants of concern. This work focuses on inducing potent immune responses against conserved regions of the SARS-CoV-2 spike protein, in addition to highly conserved non-spike targets.

Universal Influenza Virus Vaccines

Universal influenza virus vaccines aim to protect against multiple viral strains and subtypes through the induction of broadly reactive immune responses. This can be achieved by targeting conserved influenza virus proteins, with the aim of generating influenza virus vaccines that do not require annual re-formulation and re-administration. My research targets the conserved portion of the influenza viral haemagglutinin (HA), termed the HA stalk domain, using novel Ad vectored vaccine approaches. This strategy negates the issues associated with egg-based influenza vaccine production and the uncertainty of matching influenza vaccine strains to the seasonal circulating strains.

My Research Goals

1. Generating Ad vectors that can circumvent pre-existing Ad-based immunity, whilst inducing broad and potent immune responses against the encoded viral or cancer antigen. 
2. Harnessing immunogenic, virus-specific T cells as a cancer immunotherapy tool, using tumour targeting adenoviral vectors and a range of anti-cancer readouts. 
3. Evaluating mucosal and systemic immune responses against conserved influenza and SARS-CoV-2 antigens, through quantification and phenotyping of antibody and T cell responses in lung tissue, bronchoalveolar lavage fluid, peripheral blood and the spleen, and elucidating their functional profile and mechanisms of action through epitope mapping and viral challenge studies. 

Teaching

• Supervise undergraduate and Professional Training Year (PTY) student projects.
• Supervise PhD student projects.
• Tutor for medical PRE-SSC student projects. 
• Provide PhD student feedback as part of ECR-PhD student pairing programme.
• Deliver postgraduate student seminars.
• Examination marker. 
• PhD student mentor. 

Biography

I completed a BA in Biological Sciences at the University of Oxford, and subsequently worked as a Research Assistant at the University’s Jenner Institute where I performed extensive immunological testing of human peripheral blood T cells as part of clinical vaccine trials against malaria. This included multiple overseas placements at MRC laboratories in The Gambia and Wellcome Trust laboratories in Kenya, in addition to rapid response clinical testing of Ebola virus vaccines during the 2014 outbreak.

My PhD focussed on immune responses to vaccines against malaria, specifically using poxviral and chimpanzee adenoviral vectored vaccines. My research explored the immune responses induced by vaccination in both adult and paediatric cohorts. This included the development of a novel in vitro assay to measure antigen-specific CD8+ T cell killing of malaria-infected hepatocytes, and a fully validated whole blood intracellular cytokine staining assay for roll-out at clinical vaccine testing field sites in sub-Saharan Africa.

A shift of focus as a Postdoctoral Research Scientist at the Nuffied Department of Experimental Medicine (University of Oxford) led me to evaluate adaptive cellular responses following clinical administration of candidate vaccines against hepatitis C virus, with particular focus on T cell phenotype and proliferation, in addition to pre-clinical animal model development. A Postdoctoral Research Fellow position at the Icahn School of Medicine at Mount Sinai Hospital (New York) furthered my interest in viral pathogens, with particular focus on influenza A virus. My pre-clinical research explored the use of human adenovirus type 5 (Ad5)-based vaccine vectors to induce broadly reactive cellular and humoral immune responses against the influenza haemagglutinin as an approach for universal influenza virus vaccine development. My research extended to the evaluation of human T cell responses following “chimeric inactivated” and “chimeric live-attenuated” universal influenza vaccine candidates undergoing Phase I clinical testing.

I joined Cardiff University as a Wellcome Trust Institutional Strategic Support Fund (ISSF) Fellow, researching pre-clinical universal vaccine development against respiratory pathogens, and now extend this vaccine research to cancer as a Lecturer in Cancer Immunology in the Division of Cancer and Genetics. Specifically, my research aims to induce broadly cross-reactive adaptive immune responses against conserved antigens within influenza virus or SARS-CoV-2. I utilise rare species adenoviral vectors with low seroprevalence and Ad5-based vector pseudotypes, which aim to circumvent pre-existing adenovirus immunity from highly seroprevalent adenoviruses such as Ad1, Ad2, Ad5. My interests include the identification of functional immune subsets at mucosal sites that can be induced by vaccination and which underpin protection from infection and disease. This work is directly linked to the development of novel cancer therapies using adenoviral vectors, with strategies designed at directly inducing anti-cancer cellular immune responses through vaccination, or by re-directing anti-viral, vaccine-induced T cells against epithelial tumours. I work closely with many research groups within the School of Medicine, particularly those from the Division of Cancer and Genetics, for adenoviral vector development and engineering, and from the Division of Infection and Immunity, for vaccine evaluation and immunological phenotyping.

Awards and Honours

• 2022: Completion of Welsh Crucible Programme if Personal, Professional and Leadership Development. 
• 2020: Awarded Best ECR Oral Presentation at Infection & Immunity Annual Meeting (Cardiff, UK).
• 2020: Awarded Centre of Excellence for Influenza Research and Surveillance (CEIRS) Training Grant.
• 2019: Awarded  Multidisciplinary Digital Publishing Institute (MDPI) Vaccines Travel Grant.
• 2019: Awarded  MDPI Antibodies Excellent Young Researcher Certificate.
• 2014-2019: Awarded British Society for Immunology International Travel Grants.
• 2016: Awarded scholarship for Molecular Approaches to Malaria conference (Lorne, Australia)
• 2013: Awarded scholarship for Ceppellini Advanced School of Immunology meeting (Naples, Italy).

Professional Memberships                

• 2020 - present: Member of British Society for Gene and Cell Therapy, including elected Board member role.
• 2018 - present: Member of Microbiology Society
• 2012 - present: Member of British Society for Immunology

Internal Committees

• 2021 – present: Seminar series organiser for Institute of Cancer & Genetics, Cardiff University.
• 2021 - present: Member of Network for Researcher Development (NeRD) Organising Committee at Institute of Cancer & Genetics, Cardiff University.

External Committees

• 2024: Local organising committee member for British Society for Gene and Cell Therapy (BSGCT) annual meeting.
• 2023: Scientific committee member for 15th International Adenovirus Meeting. 
• 2023-present: Elected to the executive board of BSGCT, and co-chair of the Communications and Promotions subcommittee. 
• 2023: Local organising committee member for BSGCT annual meeting. 
• 2022: Local organinising committee member for the European Society for Gene and Cell Therapy 2022 congress.
• 2021 - present: Editor at Frontiers in Immunology; Vaccines and Molecular Therapeutics.
• 2020 - 2023: Co-chair of the BSGCT Early Career Development and Collaboration subcommittee 
• 2020 - 2023: Early Career Researcher on the executive board for the BSGCT.
• 2018 - present: Regular manuscript reviewer for a range of peer-reviewed journals.

Supervisions

I currently supervise:

• Ms Daisy Adamson - Cardiff University, UK. Undergraduate Professional Training Year (PTY) student; Evaluating immune responses to adenoviral vectored vaccine antigens following intramuscular and intranasal delivery. 
• Ms Rebecca Wallace – Cardiff University, UK. PhD student funded by Cancer Research UK; Development of precision virotherapies capable of evading anti-vector immunity.
• Ms Rosie Mundy - Cardiff University, UK. PhD student funded by GW4; Structural and biological insights into novel adenovirus based platforms for therapeutic applications.

I have previously supervised:

• Ms Aimee Lucignoli – Cardiff University, UK. Undergraduate Professional Training Year (PTY) student; Re-targetting SARS-CoV-2 cellular immunity towards cancer.
• Ms Caitlin Dop – Cardiff University, UK. 3rd year Pharmacology Research Project student; Evaluating pre-clinical immunogenicity of adenoviral vectored vaccines encoding SARS-CoV-2 non-structual proteins. 
• Ms Hannah Sharpe – University of Oxford, UK. PhD rotation funded by Wellcome Trust studentship in Infection, Immunology and Translational Medicine (IITM); Characterising the T cell response of rats infected with a rat hepacivirus.
• Ms Caitlin Dop – Cardiff University, UK. Undergraduate Professional Training Year (PTY) student; Designing broadly reactive vaccines against SARS-CoV-2 using adenoviral vectors.

I am interesting in supervising students in the areas of:

• Adenoviral vector platforms for gene delivery.
• Anti-vector immunity to vectored vaccines.
• Cancer immunotherapies. 
• Vaccine immunology and pre-clinical testing.
• Immunity against viral pathogens.

Engagement

I am currently an Early Career Representative on the Board of the British Society for Gene and Cell Therapy (BSGCT) and participate actively in the society’s work both with researchers and the public, including contribution of lay blog articles on gene and cell therapy to the society's website (https://www.bsgct.org/education/bsgct-blogs.aspx). I have spoken at multiple outreach events: Development and Alumni Relations Showcase seminar at Cardiff University (https://www.youtube.com/watch?v=h3PRkiJ0KEM&t=1370s); Welsh Government's celebration of International Women's Day (https://www.youtube.com/watch?v=57IGp8cdA80); Merthyr Tydfil "Lates" session on vaccines; and and have given interviews on student radio and national television on the topic of vaccine development. I have hosted primary and secondary school student work experience placements in both the UK and USA, and am currently a mentor for PhD students. I have contributed to public engagement events such as World Hepatitis Day at the John Radcliffe Hospital in Oxford, and I maintain an active social media presence with promotion of accessible scientific events, materials and articles.