New study explains how adjuvant AS01 initiates immune response in humans

Opens the door for broader use of AS01 in vaccines and to streamline vaccine development.

A recent study, published in The Journal of Clinical Investigation, has used a new technique to explain how a vaccine adjuvant, an immune stimulant called AS01, activates the immune response in human lymph nodes. It has also shown that, unlike other adjuvants, the effectiveness of AS01 is not limited by age. AS01 is a key component of the shingles vaccine, Shingrix™, which is highly effective, across all adult ages.

This finding highlights the potential for AS01 to be used in vaccines to benefit a wider age range. The new technique, used by a team based at The Westmead Institute for Medical Research (WIMR) and affiliated with the University of Sydney, could be used to screen new formulations to help streamline vaccine development.

Adjuvants are substances that enhance the body’s immune response.  Adjuvants are added to a range of vaccines to increase their efficacy and durability, particularly for the ageing and immune-compromised people.

AS01 is currently used in vaccines for shingles and respiratory syncytial virus (RSV), both for older adults, as well as a malaria vaccine for children.

Professor Tony Cunnigham AO, one of the lead authors on this study explains, “Over the past decade there have been two major advances in the development of vaccines for important viral illnesses: RNA vaccines for COVID and the combination of a single viral protein with an immune stimulant, or adjuvant, which enhances the correct immune pathway to combat the disease.

“Recombinant Zoster Vaccine (RZV) for shingles, a painful disease of the ageing, is the supreme example of the latter. It is a paradigm for immunisation in our ageing populations, achieving a remarkable efficacy of more than 90%, even in those over 80 years of age. In this population, it is effective for more than 10 years, currently exceeding by far all other vaccines in this age group.

“These remarkable attributes are provided by the ‘adjuvant system’, AS01, consisting of two molecules stimulating the immune response in different ways. It has also been incorporated into vaccines for the major winter pathogen, respiratory syncytial virus and malaria (the latter with a lesser response). To understand how to improve and best use this remarkable adjuvant, its mechanism of action needs to be determined.”

The WIMR research team set out to discover how this vaccine adjuvant initiates immunity in humans. Vicki Stylianou is the first author on the research paper.  At the time of the study, she was a student at the University of Sydney and completed her PhD at WIMR. While at WIMR, Vicki was supervised by senior researchers, Professor Tony Cunningham AO and Dr Kerrie Sandgren, who are also lead authors of this study.

The new approach developed by the WIMR team used tissue samples from human lymph nodes that were donated by patients who had undergone lymph node dissection for breast cancer at Westmead Hospital.

Vicki Stylianou says, “We exposed the intact lymph node tissue samples to vaccine adjuvants, and this revealed responses that had previously not been detected using other methods.

“We then used this method to look more closely at adjuvant AS01. We discovered that the immune system’s response to AS01 requires a coordinated activation of lymph node cells.”

Dr Kerrie Sandgren explains, “We found that AS01 kickstarted a cascade of controlled inflammation in the lymph node tissue that magnified the resulting protective immune response. Working with the lymph node tissue was critical as we did not see these responses when we removed the cells from the tissue or looked in blood.”

Professor Tony Cunningham says, “Unlike the lymph node response to other adjuvants, the response to AS01 was not dependent on the age of the adult donor. This might explain why AS01 adjuvanted vaccines, like Recombinant Zoster Vaccine (Shingrix™), are remarkably effective in older adults. This finding could open up the use of AS01 to a range of other vaccines.

“This study has also shown that this new approach of exposing human lymph node tissue samples to vaccines is a valuable tool for studying how adjuvants work in humans, and is a potential new tool for screening new formulations to help streamline vaccine development.”

CATEGORIES