World-first human challenge trial of Strep A vaccine

Strep A is a highly virulent organism with multiple strains, factors that help it subvert immunity and that have hampered previous vaccine research.

Professor Michael Good AO, Associate Professor Manisha Pandey and their team from Griffith University’s Institute for Biomedicine and Glycomics have identified two small molecules, known as epitopes, that are present on every Strep A strain.

By combining these molecules, they were able to create a vaccine capable of enhancing the body’s natural immune response.

“There is currently no vaccine available for Strep A, and natural immunity takes years to develop,” said Professor Good AO.

“My team has developed what we hope will be the world’s first vaccine to market for the prevention of diseases caused by Strep A infection.”

The team’s research includes two vaccine approaches.

The lead candidate currently in human clinical trials at the University of Alberta in Canada is a typical vaccine formulation that includes an aluminium adjuvant. Early results from the trial, in which the vaccine is being tested for safety and immunogenicity, are very encouraging.

The second approach employs an innovative way to deliver the vaccine by the nose.

For many, Strep A infections may be associated with relatively benign conditions such as tonsillitis and impetigo (school sores).

However, Strep A kills an estimated 500,000 people each year worldwide, and untreated or repeated infections can lead to life-threatening diseases such as rheumatic fever, rheumatic heart disease, inflammation of the kidneys, necrotising fasciitis (flesh eating disease) and toxic shock syndrome.

While Strep A and its associated diseases can affect people of all ages and socio-economic levels, they are particularly devastating for First Nations peoples and developing countries. In Australia, First Nations peoples have a high rate of both rheumatic fever (92% of the 2,784 new cases that occurred between 2017-2021) and rheumatic heart disease (78% of the nearly 7,000 people registered as of 31 December 2021).

A recently received $5 million philanthropic donation from the International Leducq Foundation will move the vaccine into the next stages, including a human clinical trial at the Murdoch Children’s Research Institute, Melbourne, Australia. In this trial volunteers will be vaccinated and then given a deliberate, controlled dose of Strep A to test the vaccine. A separate trial will then use a comprehensive testing strategy to identify the optimal dose of the vaccine to take into a Phase II clinical trial, where hundreds of children will be vaccinated and followed to test the efficacy of the vaccine in a real-world setting.

Dr David Milan, Leducq Chief Scientific Officer, said supporting this effort to develop a Strep A vaccine falls squarely within the cardiovascular disease mission of the Leducq Foundation.

“Leducq is excited about the potential of a Strep A vaccine to reduce not only Strep A throat infections but downstream rheumatic heart disease, a major source of worldwide mortality, especially in low- and middle-income countries,” said Dr Milan.

If the trials are successful, the vaccine could be available within five years.

“Not only does this vaccine give hope in the fight against Strep A, but in future, the vaccine nasal delivery platform could pave the way for other vaccines against mucosal pathogens,” said Professor Good AO. “My team and our collaborators will continue to strive towards preventing such serious diseases.”

The vaccine currently progressing through a human Phase 1 clinical trial in Canada has been made possible thanks to the generous support of the Heart Foundation, the Li Ka Shing Institute (Canada), the Snow Foundation, the National Health and Medical Research Council (NHMRC) and the National Foundation for Medical Research and Innovation.