As of 16 December, at least 19 children have died in the UK in recent months from an invasive infection of strep A bacteria. On a global scale, the bacteria kill more than half a million people each year. Many of these deaths could be prevented by a vaccine 鈥� so why don鈥檛 we have one?
Strep A is a bacterium known as聽. It is best known for causing a sore throat, so-called strep throat, and scarlet fever. In rare cases, the bacteria can also cause invasive infections that affect internal organs, which is what killed the children in the UK.
On top of this, the bacteria can cause the flesh-eating condition necrotising fasciitis or lead to puerperal sepsis, an infection of the genital tract following birth, which is one of the main causes of maternal deaths worldwide. Most strep A-related deaths, however, are a result of the infection triggering an autoimmune response known as rheumatic fever, which damages the heart and sometimes the kidneys.
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The true toll of strep A is probably much more than . Due to a lack of testing and case reporting in many countries, that number is considered an underestimate, says at the University of Tennessee Health Science Center.
A vaccine could greatly reduce strep A鈥檚 death toll and spare many more from its rare but serious complications. Despite this, no major vaccine manufacturer has tried to get a vaccine approved, says Dale. As is often the case, companies may not think a strep A vaccine would be profitable.
One reason is that strep A is treatable with penicillin, so pharmaceutical companies may not see the need for a vaccine. But the widespread use of penicillin for strep A 鈥� mostly as a precaution against serious complications 鈥� is contributing to resistance both in strep A and in other bacteria.
鈥淭here is evidence that group A sensitivity [to penicillin] is decreasing,鈥� says Dale. Penicillin is known to be effective and safe, as well as relatively cheap. Other antibiotics could be used instead, but it would be far better to reduce our reliance on antibiotics via vaccines, says Dale.
Another issue is that it is unclear how strep A causes the autoimmune response behind rheumatic fever. The vaccine candidates could therefore trigger this response in some people during trials. That isn鈥檛 a risk companies want to take, says Dale.
Then there are the technical challenges. An obvious target for vaccines is the so-called m protein found on the outside of the bacterium, which helps it fend off attacks by the immune system. However, there are more than 200 variants of the m protein and its diversity is highest in the low-income countries where vaccines are most needed, making it hard to develop a single vaccine that works against all strains.
To try to solve this, Dale鈥檚 team has developed candidate vaccines that contain around 30 variants of the m protein. Animal studies suggest the candidates would trigger .
Another candidate vaccine, developed by at Griffith University in Queensland, Australia, and his colleagues, targets part of the m protein that is shared among almost all strep A strains.
Since the World Health Organization (WHO) highlighted the need for a strep A vaccine in 2018, more research institutes have turned their attention to the issue, says at Imperial College London, who is part of the .
鈥淚 think the WHO recommendation prompted many [non-commercial] funders to think again,鈥� she says. 鈥淎 number [of vaccine candidates] are progressing to clinical studies in the next couple of years.鈥�
Dale agrees there have been advances on the technical side, which could be accelerated by mRNA technology. mRNA vaccines are much cheaper and faster to manufacture than other vaccine technologies, which speeds up every stage of their development and rollout. 鈥淭he mRNA platform is going to dramatically alter vaccine development,鈥� he says. For now, though, there are no trials for mRNA vaccine candidates for strep A.
The strep A vaccine candidate trials that are lined up are small ones, designed to test safety. For instance, Good鈥檚 vaccine is being . With vaccine manufacturers reluctant to fund trials, it is unclear how any success in such small, initial trials can lead to funding for the much larger and more expensive ones that are needed to establish efficacy and ultimately get approval.
鈥淲e鈥檝e not made any progress in the way of large vaccine manufacturers and their hesitancy to take these on,鈥� says Dale.
