mRNA offers new hope to Strep A vaccine development
The funding will allow researchers from the University of Queensland – along with partners from Moderna – to conduct and complete preclinical trials with the goal of reaching the clinic in the next three years.
Strep A vaccine challenges
There is no vaccine for the prevention of Strep A, which causes strep throat and scarlet fever and is a major driver of antibiotic use in children. Repeated infections can lead to rheumatic heart disease, the most significant cause of childhood death due to heart failure.
Strep A vaccine development has been ongoing for decades: and yet has been hindered by a number of factors
Controversy around a 1978 study resulted in an US FDA ban on subsequent vaccine trials: stalling development for 30 years until this was overturned.
Other factors include the complexity of the epidemiology and Strep A infections – there are more than 200 serotypes - and concerns about potential efficacy and vaccine coverage. There has also been a lack of commercial interest and reluctance to invest: over questions about the size of the market in high-income countries.
However, as well as addressing the 500,000 premature deaths a year which are associated with Strep A infections and their most serious complications, a vaccine would also limit the use of antibiotics and the spread of antibiotic resistance.
With the support of the Leducq Foundation, the University of Queensland is now setting out to complete pre-clinical studies in animal models for the mRNA candidate: in the hope of taking the vaccine into the clinic in the next three years.
An mRNA vaccine could offer advantages in two key areas. Firstly – as with other mRNA vaccines and demonstrated with COVID-19 vaccines – the approach can simplify the manufacturing process.
But secondly, it could also offer advantages where other technologies have struggled. The researchers think the mRNA vaccine will stimulate the right kind of protective immunity for a Strep A vaccine.
Meanwhile, another of the challenges for Strep A vaccines has been perceptions of the risk of autoimmune complications triggered by vaccines: specifically from the M protein and group A carbohydrate.
The mRNA vaccine formulation, in contrast, does not contain either of these antigens.
Efficacy data from the team’s pre-clinical studies is described as ‘promising’: with researchers confirming that the five vaccine antigen combination with an experimental adjuvant provides protective immunity in preclinical animal models.
The next step is to confirm pre-clinical efficacy with an mRNA formulation.
The team includes researchers from UQ, the University of Melbourne, the Murdoch Children’s Research Institute, Emory University, CONACYT and mRNA pioneer Moderna: which will help with vaccine manufacture and could one day commercialize the vaccine.
Other Strep A vaccine candidates include:
- StreptAnova: a 30-valent vaccine developed by the University of Tennessee & Vaxent completed a Phase 1 study in 2020 demonstrating significant immunogenicity towards most of the targeted antigens.
- J8-K4S2 and p*17-K4S2: In November, researchers from the University of Alberta (Canada) and Griffith University (Australia) announced they have taken their peptide-based candidate into clinical trials.
- StrepInCor, a peptide vaccine from the University of Sao Paulo, Brazil, has been shown to elicity protective immunity in mice.