Auckland scientist Dr Jacelyn Loh is developing a vaccine to prevent rheumatic fever – a disease killing and maiming New Zealanders. When could that breakthrough happen? The answer could depend on funding.
In a lab across from Auckland Hospital, a scientist steadily works towards a world-first vaccine for a Third World disease that still claims well over 100 lives every year in New Zealand.
Dr Jacelyn Loh’s TeeVax vaccine works to boost the immune system to fight off infections from Group A streptococcus bacteria, including “strep throat”.
If untreated, those infections can trigger an autoimmune condition called acute rheumatic fever, which inflames and damages heart valves, resulting in disability and early death – often decades later.
On average, about 140 New Zealanders die from rheumatic heart disease every year.
Māori and Pacific children and teenagers make up nearly all cases of rheumatic fever. Symptoms include a high temperature, joint pain, tiredness and breathlessness.
Its persistence has been called a national shame because the disease is closely associated with poverty, including low-quality, overcrowded housing.
Loh is reformulating TeeVax and has found combinations that should significantly boost the protection it offers.
The next step will be more animal studies to confirm that. Further along, finding the millions of dollars needed to conduct clinical trials in humans will be a daunting challenge.
“I think there is hope, certainly,” said Loh, who balances research with raising two boys, aged 8 and 10.
“It’s a constant cycle. We go back, we redesign, then we retest.”
Why NZ has high rheumatic fever rates
Global rheumatic fever rates dropped away as living standards rose. New Zealand is now just one of three developed countries where the disease has a foothold (the others being Australia and Canada, where the disease mostly affects Aboriginal and Torres Strait Islanders, and First Nations peoples.)
In Aotearoa, it almost exclusively affects Māori and Pacific (mostly Samoan and Tongan) young people aged 4-19 years, who experience rheumatic fever rates otherwise only seen in Third World nations.
One study found that even when adjusted for age, sex and socio-economic deprivation, hospitalisation rates are about 24 times higher for Pacific and 12 times higher for Māori, compared to European and other ethnicities.
In some areas the difference is even bigger: the risk of initial hospitalisation in Auckland is increased 240 times for Pacific peoples, and 87 times for Māori.
A November 2021 report by the Office of the Prime Minister’s Chief Science Adviser found there were multiple and interwoven reasons for the disease’s spread (some of which aren’t yet well understood), including poverty, poor quality housing, overcrowding, and problems accessing healthcare, including because of systemic racism.
“The exact reasons for the increased risk among these ethnicities are likely to be complex and multifaceted,” the report stated.
“[One study] clearly demonstrated that Māori and Pacific peoples from the least deprived areas still had higher risk than European, Asian or other ethnicities from the most deprived areas.
“In addition to being a disease of concern itself, rheumatic fever is a symptom of broader health inequities.”
Antibiotics can usually cure throat infections. However, not every child or young person has a sore throat before developing rheumatic fever (up to 50 per cent don’t recall having a sore throat in the weeks prior, one study estimated).
Even if symptoms are present, they can be misdiagnosed. Most sore throats are caused by a viral infection, for which antibiotics should not be prescribed, including to limit the worsening risk of antimicrobial resistance.
Less than 3 per cent of people with untreated strep throat develop rheumatic fever, but those who do are more likely to have another episode.
Each autoimmune attack causes inflammation in the heart. When that resolves, the damage remains. People suffer heart failure, arrhythmia, increased risk of infection, stroke, problems in pregnancy, and early death.
Further rheumatic fever and heart complications can be prevented by monthly and painful injections of penicillin into the buttocks – an ordeal repeated for at least 10 years.
Sick children and teens often have to take long breaks from school, and can have life-long health complications and repeat heart operations.
About 150 New Zealanders have a first episode of rheumatic fever each year, and around 270 people are diagnosed with rheumatic heart disease – mostly adults whose infection happened years or decades earlier, when they were a child or teenager.
The true burden is likely much greater – previous screening of Pacific young adults in South Auckland found 1 in 50 may be living with rheumatic heart disease.
The race for a rheumatic fever vaccine
Preventing that suffering has been a focus for the Cure Kids NZ charity, which for more than 50 years has funded child health research.
Almost $680,000 has gone to a small team led by Dr Loh, a senior research fellow at the University of Auckland.
Her vaccine work began after she returned home to New Zealand in 2013, following several years in Switzerland working on immunotherapies to treat brain cancer.
Back in Auckland, she worked with Thomas Proft, a Professor in Molecular Medicine and Pathology and leading researcher on Group A streptococcus.
He was studying pili, which are thin, hair-like proteins on the bacterial cell surface.
They were only discovered on Group A streptococcus in 2005, and it’s now known they play an important role in infection by helping the bacteria stick to the throat, or skin.
Pili are multimeric structures – lots of proteins joined together, like beads in a chain. Different strains of Group A strep bacteria have many different types, Proft helped confirm.
“That was a concern, because obviously we wanted our vaccine to cover all the strains, rather than just a few,” Loh said.
They took T-antigen proteins – or individual beads – from different pili, and joined them together, to make new, fused chains.
These work to prime the body’s natural response to an infection, in which white blood cells (lymphocytes) are produced to destroy infected cells.
This happens in response to specific antigens on the surface of pathogens.
Loh’s vaccine introduces multiple, fused T-antigen proteins to trigger this process.
If that person was later infected with Group A streptococcus, the aim is that their immune system would be trained or primed to create antibodies to fight off the pathogen.
“It’s like a tag – the antibodies can tag the bacteria to tell the immune system that it’s bad, and then they’ll kill it.”
In 2018, Loh went to Brisbane to test the vaccine in mice. The animals were vaccinated, then infected with Group A strep under their skin.
“It wasn’t complete protection from disease,” she said of the results. “But we did see about 50 per cent of the mice protected.”
Since then, Loh has worked on reformulating the vaccine, adding extra ingredients to try and boost its effectiveness.
These include liposomes, which are tiny droplets or nanoparticles of fat, and act as a delivery system to help the body produce more antibodies in response to the vaccine.
“We’ve found some formulations that make way better antibodies, as well as some T-cell responses, which are good at creating long-lived immunity.”
Those will be tested in another mouse trial. It could then be possible to move to clinical trials in humans – but just getting the high-grade material produced would cost millions of dollars, and many millions more to conduct the actual, multi-phase trials needed to prove efficacy.
When could a rheumatic fever vaccine be ready?
More funding is needed for the full animal protection studies, which could happen in the next few years.
Proft supports Loh in an advisory role, and she has a senior research technician, Adrina Khemlani, who helps her in the laboratory.
“And any postgrad students we can get at the time. Obviously, if we had money to fund more technicians, we could certainly speed up the process.”
The entirety of Loh’s salary is paid externally from the university – through grants and funding from groups like Cure Kids and the Heart Foundation.
“My funding runs out in June. I am applying to various sources. My technician is also funded through research grants,” she said.
“It is a funny way to work. You aren’t guaranteed that you can continue, even though you plan your experiments longer-term.
“It can be stressful. You spend a lot of time writing grant applications, when you really wish you could just do the research. It is tricky to balance. But many other researchers are in the same boat.”
Last November, the Government announced $10 million to help University of Auckland’s medical faculty to collaborate with a rheumatic fever vaccine programme under development in Australia.
The Australian Strep A Vaccine Initiative (ASAVI) is preparing to fast-track a vaccine into human trials.
A number are being developed internationally, and the initiative is not tied to any particular project – just whichever is promising and ready. (TeeVax could be considered, for instance.)
In announcing the funding, then Health Minister Ayesha Verrall said it would ensure that any vaccine progressed through ASAVI would cover the Strep A strains circulating in New Zealand.
“As an infectious diseases doctor, I cared for rangatahi who experienced some of the worst outcomes from this illness,” she said at the time.
“Several had heart valve replacements that became infected, and some suffered strokes. One young woman needed a heart transplant, and later tragically died.”
The money would also support enhanced surveillance of Group A streptococcus, Verrall said, “and preparations to ensure Aotearoa New Zealand is ready to conduct clinical trials”.
No funding went directly to Loh’s work. Other vaccines are progressing in Australia and the United States, including some that have completed phase one clinical trials.
However, hers is the only T-antigen version, which holds promise to more easily cover the hundreds of bacteria strains circulating globally.
“We are getting New Zealand information about New Zealand strains. And so that really helps us design our vaccine better,” she said.
“We might alter it in future to make sure we cover any new variants that might arise in New Zealand. So having those close links I think is really important.”
Loh is investigating a possible mRNA vaccine, which would use genetic code to teach cells how to make a protein that triggers an immune response.
Crucially, that would be much cheaper to produce for clinical trials.
Rheumatic heart disease in our hospitals
In the meantime, disease continues to spread. In the 12 months to December 31, 2022, there were 82 people admitted to hospital for the first time with rheumatic fever, a drop from 93 in the previous 12 months.
The Ministry of Health, which is helping lead a new rheumatic fever “roadmap” to try and bring down rates, will publish new figures soon.
Its most up-to-date figures for deaths from rheumatic heart disease is 136 in 2020, although there can be a reporting lag while coroner’s reports are done.
Dr Sarah Fairley, a cardiologist at Wellington Hospital, sees that toll close up.
Her specialties include obstetric cardiology (high-risk cardiac pregnancies), and a number of women need treatment because of damage caused years earlier by an “entirely preventable illness”.
“In New Zealand in 2023, we should not still have to manage the complications of rheumatic fever and rheumatic heart disease,” said Fairley, who spoke to the Herald in her role with the Cardiac Society, the professional body for cardiologists.
“I trained in the UK and Ireland, I never encountered rheumatic heart disease and thought it was something we read about in textbooks.
“Unfortunately, it remains a problem in New Zealand… I would challenge the new Government that it should be a focus for them to address.”
For her part, Loh is working day-in, day-out, towards a breakthrough. When could that happen?
“It is really difficult to say. Obviously, I hope as soon as possible… getting to clinical trials, I would say is a minimum of three years away.
“We are testing quite a few different formulations. We don’t have enough funding to test all of them, so we are going with our best guess.”
Nicholas Jones is an investigative reporter at the Herald. He won the best individual investigation and best social issues reporter categories at the 2023 Voyager Media Awards.
