Active Infection & Immunity Lungs & Breathing

Investigating the impact of pre-existing adenovirus immunity on the safety and efficacy of adenoviral-based vaccines and therapeutics

Funder Wellcome Charity-funded
Recipient organisation University of Liverpool
Funding £713K
Period Nov 2025 — Nov 2030

In plain English

AI plain-English summary

Adenoviruses that most people have already been exposed to through common colds can cripple the performance of vaccines and gene therapies built from the same viral backbones. This matters because the Oxford COVID-19 vaccine and many experimental gene therapies use adenovirus vectors, but pre-existing immunity from natural infection—and cross-reactivity between different adenovirus types—can blunt their effectiveness and may contribute to rare adverse events. The researchers will first map the specific T-cell targets that the immune system remembers from past adenovirus infections, using blood samples from healthy donors and from patients who experienced vaccine side effects. They will then test whether those cross-reactive T-cells actually reduce vaccine performance in the lab. Finally, they will redesign the viral vectors themselves—engineering out the immune-triggering regions—so that the body’s memory response no longer attacks the therapy before it can work. If successful, this fundamental redesign of adenovirus vectors could make future vaccines more reliable and gene therapies safer for people who have already been infected with common cold viruses. The work is primarily fundamental science, clarifying how the immune system’s memory of past infections interferes with engineered viral delivery systems, but it directly underpins the next generation of viral vectors for global health.

View original technical description
My research programme aims to improve the safety and efficacy of adenoviral vector-based vaccines and therapies by introducing a fundamental shift in vector design. Human adenoviruses are routinely used as delivery vectors for gene therapies and vaccines. Human adenovirus serotype 5 (HAd5) was the backbone of adenoviral vector development. However, concerns have been raised regarding future suitability due to the high prevalence of pre-existing immunity. Prior exposure to circulating human adenovirus through natural infection can hamper vaccine and therapeutic performance. In addition, immune cross-reactivity is widespread between conserved proteins of HAd5 and non- human adenoviral vector alternatives, such as the Oxford COVID-19 vaccine (ChAdOx1). Key goals: First, we will identify and characterise conserved immunodominant T-cell epitopes shared across adenoviral vector vaccines and circulating human adenoviruses of high seroprevalence using healthy donor models and patients with vaccine-mediated adverse events. Second, we will evaluate the impact of cross-reactive adenoviral T-cell epitopes on vaccine performance and assess the clinical significance of adenovirus cross- reactivity. Lastly, we will engineer modified adenoviral vectors to evade T-cell immunogenicity and off-target immune stimulation. Through innovative modifications that mitigate immunogenicity, this work will broaden therapeutic applications, improve efficacy and underpin the development of next generation adenoviral-based vectors.

View the original record at the funder ↗

Researchers

Joshua Gardner (EPMC Awardee)

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Original classification

Early-Career Award

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