Trinity scientists’ discovery offers ‘significant hope’ for improved vaccines

Better vaccine adjuvants can enhance cell mediated immune responses — and Irish researchers may have discovered a new way of measuring them

Scientists in Trinity College have discovered a ‘Goldilocks’ effect in identifying the size of a ‘vaccine adjuvant’ that can trigger strong immune responses and, as an example, have shown that a safe, biodegradable adjuvant can boost the action of cancer-killing cells — if the particles are the correct size.

The discovery has ‘wide-ranging implications’ for the design of new, improved vaccines that are badly needed to enhance cell mediated immune responses against cancers and a host of infectious diseases.

Professor Ed Lavelle, from the Trinity Biomedical Sciences Institute, is the senior author of a research article outlining the discovery. It was published this week in the journal Cell Reports Medicine.

“To allow the rational design of vaccines we need to know what the rules are governing how adjuvants activate different types of immune response,” he said.

Professor Ed Lavelle, of the Trinity Biomedical Sciences Institute

“If we have that crucial info, we can then tailor vaccine development for specific applications, as the responses required depend on the disease — one size does not fit all.”

Adjuvants are essentially ‘special ingredients’ that enhance the effectiveness of a vaccine, for example by boosting killer T cells or antibody production. This results in longer-lasting immunity, or in reducing the dose of active agent — the ‘antigen’ — needed in the vaccine.

Scientists have been hunting for better adjuvants that enhance cell mediated immune responses. One key application of such adjuvants would be eliciting cytotoxic T cells that can kill tumours and virally infected cells.

Natalia Munoz-Wolf, Research Assistant Professor in Trinity’s School of Medicine, and Ross Ward, a PhD student in the School of Biochemistry and Immunology, are first co-authors of the research article.

Natalia Munoz-Wolf, Research Assistant Professor in Trinity’s School of Medicine

They say they have established that the size of adjuvant particles is critical for determining the induction of cell-mediated immune responses — including the action of cytotoxic T cells – and that a biodegradable polymer can be used to develop a highly effective adjuvant that promotes cytotoxic T cells if the particles are the correct size.

The scientists also say they have shown for the first time that nanoparticles of around 50 nm in size can activate a signalling pathway called the non-canonical inflammasome that allows the induction of effective cell mediated immune responses.

“We propose that small nanoparticles like this promote reactive oxygen species in cells, which in turn lead to the activation of key components of this pathway including caspase 11 and gasdermin proteins, which are essential for generation of cell mediated immunity,” the pair said.

In combination their work represents a ‘significant step forward’ in the development of next-gen adjuvants for improved anticancer and antiviral vaccines.

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