For patients with advanced melanoma without BRAF mutation who no longer respond to immune checkpoint inhibitors, treatment options remain frustratingly limited. A new study from Vanderbilt researchers led by Professor Emerita of Pharmacology Ann Richmond outlines a promising therapeutic strategy that may re-sensitise these resistant tumours to immunotherapy.
Figure 5b from the paper shows the difference between tumours treated with a just an antibody and vehicle (solution) or with trametinib and rigosertib and a CD40 agonist. Image cropped and shared from the paper by Yan et al. published in Nature Communications in 2026 in accordance with a CC BY-NC-ND 4.0 license.
The research introduces a three-drug combination that enhances immune activity and suppresses tumour-promoting immune cells by leveraging a low dose of the MEK inhibitor trametinib and multi-kinase inhibitor rigosertib alongside a CD40 agonist to shift the tumour microenvironment toward immune activation. Notably, all three agents have been either approved by the U.S. Food and Drug Administration or are currently in clinical trials, which may speed their path to patient testing.
“While agonist CD40 therapy can be helpful for treatment of melanoma, this therapy also induces the CD11b+ B regulatory cells that suppress the T cell response to tumours,” Richmond said. “We showed that combining CD40 therapy with trametinib and rigosertib prevents the induction of these B regulatory cells.”
Immune checkpoint inhibitors have become a mainstay of melanoma treatment, working by releasing the molecular “brakes” that prevent T cells from attacking cancer. But resistance to ICI is common in metastatic melanoma, especially in tumours that evolve immune-suppressive microenvironments. While CD40 agonists can activate immune cells, this therapy also unexpectedly expands CD11b+ regulatory B cells.
By combining CD40 activation with MEK and PI3K inhibition, the researchers blocked the expansion of suppressive B cells while retaining the benefits of CD40 stimulation. In preclinical mouse models of melanoma, the triple combination not only suppressed tumour growth but also restored responsiveness to checkpoint blockade.
Key findings
B cells as a resistance mechanism: CD40 therapy alone induced regulatory B cells that dampen T cell–mediated tumor immunity.
Triple combination prevents immune suppression: Co-treatment with trametinib and rigosertib blocked the agonist CD40 induction of regulatory B cells, allowing immune responses to proceed.
ICIs regain effectiveness: The drug cocktail slowed tumor progression and re-sensitized resistant melanomas to anti-PD-1 therapy.
Translational promise
Because trametinib, rigosertib, and CD40 agonists are already in human trials or approved for other indications, this therapeutic strategy may advance more quickly than approaches requiring new drug development. Richmond’s team sees potential for testing the triple therapy in clinical trials for melanoma patients who have progressed on ICI.
“This approach provides a new route to enhance antitumor immunity in patients with tumors that no longer respond to immunotherapy,” Richmond said.
Prenatal magnesium sulfate and steroids can reduce the risks of cerebral palsy and respiratory complications in preterm infants. A review in the International Journal of Gynecology & Obstetrics found that despite being recommended internationally for pregnant women at risk of preterm delivery, these medications are used variably between and within countries.
When they analysed 2012–2024 information on 45 619 babies born at 24–32 weeks’ gestation at 1111 hospitals in an international network, along with information from the UK National Neonatal Research Database and a literature review, investigators found that on average, less than half of infants had been exposed to preterm magnesium sulfate in middle-income countries, and approximately three-quarters in high-income countries. Even within high-income countries, there were large discrepancies in care. Preterm steroids were used more frequently with less variation, although treatment gaps were still apparent.
“Our study has highlighted the international disparities in how two key treatments to protect pre-term babies are implemented. These gaps aren’t because of a lack of evidence,” said corresponding author Hannah B. Edwards, MA, MSc, of the University of Bristol, in the UK. “Lessons can be learned from successful implementation programs like PReCePT, which has transformed use of magnesium sulphate in pre-term births in England. The bigger-picture goal should now be to ensure that no matter where a baby is born, their mother has access to the evidence-based treatments that offer the best start in life.”
We’ve known for a long time that women are more likely than men to have migraine attacks.
As children, girls and boys experience migraine equally. But after puberty, women are two to three times more likely to experience this potentially debilitating condition.
Recently, an Australian study showed it may be even more common than we previously thought – as many as one in three women live with migraine.
For comparison, migraine affects roughly one in 15 men in Australia.
So, what’s behind the difference? Here’s what we know.
More than a headache
Migraine is not just a bad headache – it is a complex disorder that causes the brain to process sensory information abnormally.
This means “migraine brains” can have difficulty processing information from any of the five senses:
sight (leading to problems with light sensitivity and glare)
sound (leading to noise sensitivity)
smell (certain smells can trigger headaches)
touch (leading to face or scalp tenderness)
taste (causing distorted taste, nausea and vomiting).
Migraine attacks typically last anywhere from four hours to three days – but can be longer.
In addition to the symptoms above, attacks can include throbbing head pain, dizziness, fatigue and difficulty concentrating. It is these extra symptoms that help diagnose migraine – not the location of head pain or pain severity.
Why are attacks more frequent in women?
Puberty is when the difference between men and women emerges. This is when our bodies massively increase the production of sex hormones.
People are often surprised to learn that both men and women produce oestrogen, progesterone and testosterone. Testosterone levels are higher in men, whereas women have higher levels of oestrogen and progesterone.
However, it is not just the type of hormone that makes a difference, but the way they fluctuate over time.
For many women, there are certain “milestone moments” when their migraine tends to worsen due to hormonal fluctuations – puberty, menstruation, pregnancy and perimenopause (the lead-up to your final period).
For example, some women notice migraine flare-ups every month, linked to phases in their monthly menstrual cycle when oestrogen levels drop.
They might even be able to predict when their period will start, as migraine attacks typically start a few days before the bleeding.
How hormones affect the brain
Women with migraine can be more sensitive to hormonal changes. This is particularly the case for sudden decreases in oestrogen. But even more subtle changes to hormone levels can cause migraine attacks.
These hormonal changes can activate brain processes that trigger migraine, such as cortical spreading depression. This is a very slow wave of electrical activity that spreads in the brain, causing some areas to function more slowly than others after it passes.
Decrease in oestrogen can also affect how we receive and process information through the trigeminal nerve. This plays a key role in the onset and maintenance of migraine pain.
Oestrogen can affect how we process information through the trigeminal nerve. ttsz/Getty
All kinds of fluctuations can be a trigger
Pregnancy can often destabilise migraine again and make attacks more likely, even when someone has previously enjoyed a period of good migraine control.
Migraine symptoms often become uncontrolled in the first trimester in particular, due to rapid hormonal changes needed to sustain a pregnancy. This usually settles in the second and third trimesters, when hormonal changes stabilise.
However, giving birth is yet another change.
Towards the end of pregnancy, oestrogen levels can be 30 times higher than pre-pregnancy levels, and progesterone can be 20 times higher. When these hormones plummet back to normal after giving birth, migraine attacks can often sharply worsen again.
Perimenopause can also involve random surges of oestrogen from the dwindling supplies of eggs within the ovaries – which previously produced these hormones cyclically and in abundance. This irregular hormone production can cause random spikes in migraine attacks. It can be extra challenging when combined with other symptoms of menopause such as hot flushes or mood changes.
Hormonal contraceptives and menopause hormone therapy can also affect migraine control. Sometimes, supplementing hormones at a regular, steady daily dose can help manage the hormone-sensitive headaches and other symptoms. However, for others, adding extra hormones can cause head pain to flare up.
Does migraine run in the family?
Genes also play a role. It’s not a coincidence that migraine is passed down in families through the maternal side.
This is because mothers pass on mitochondria to children (while fathers do not). Mitochondria are parts inside the cell that control energy.
People with migraine have fewer functional enzymes within their mitochondria, meaning their brains are in an energy-deficient state. This worsens with migraine attacks as there is even more stress to the system.
This is also why extra stress (such as sleep deprivation, missed meals, or emotional stress) can trigger a migraine and worsen pain.
There is also a strong link between migraine in women and anxiety and depression – conditions women are more likely to develop in response to stressful life events.
Knowing your own patterns
If you suspect hormones may be affecting your migraine attacks, it is helpful to keep a diary of symptoms, including headaches. Mark each day per month where you get migraine symptoms, as well as your period, to find patterns.
Identifying patterns in pain flares helps doctors guide you to a personalised medication plan, which may include hormone therapies or non-hormonal therapies.
Long-term data suggests an overall cure rate of 42%
Photo by National Cancer Institute on Unsplash
Unlike some other forms of lymphoma, advanced stage follicular lymphoma is considered incurable. But a new analysis of long-term data on patients treated for the disease years ago with standard regimens of immunotherapy and a chemotherapy combination known as CHOP suggests that many of those patients can now be considered cured.
The analysis is just published in the journal JAMA Oncology.
“A subset of advanced-stage follicular lymphoma patients can achieve cure with CHOP-based chemoimmunotherapy, as relapse rates decline over time,” said Wilmot Cancer Institute Director Jonathan W. Friedberg, MD, MMSc, at the University of Rochester Medical Center, who is senior and corresponding author on the paper.
“This finding represents a paradigm shift in our understanding and approach to follicular lymphoma, with broad implications for initial patient discussions and future research strategies.”
Historically, follicular lymphoma has been considered an incurable disease, with most patients experiencing relapses even years after initial treatment.
The JAMA Oncology paper reports on an analysis of follow-up data from patients with advanced follicular lymphoma who had been treated with a standard first-line chemoimmunotherapy regimen on a large clinical trial.
Roughly 70 percent of the patients remained alive 15 years after beginning treatment, and a statistical method known as cure modelling estimated that 42% of treated patients had been cured.
Cure modelling incorporates background mortality rates in an analysis of patient survival data to estimate what fraction of a group of patients can be considered cured of a disease. Such modelling accounts for the fact that over time some patient deaths will occur that are unrelated to the given disease.
The researchers applied a cure model to 15-year follow-up data from the S0016 clinical trial conducted by the SWOG Cancer Research Network, a clinical trials group funded by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), with the participation of other groups within the NCI-funded National Clinical Trials Network (NCTN).
This phase 3 trial, which opened in 2001, enrolled patients with untreated advanced-stage CD20-positive follicular lymphoma and randomised 531 of them to one of two treatments, both of which were built around a core chemotherapy regimen known as CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone). One arm treated patients with rituximab plus the CHOP combination (R-CHOP), while the other arm used CHOP followed by radioimmunotherapy (CHOP-RIT). Primary results of the S0016 trial were published in 2013 (Press, OW. J Clin Oncol. 2013).
The S0016 modeling, including cure analysis, was carried out by Michael LeBlanc, PhD, a biostatistician at Fred Hutch Cancer Center and director of SWOG’s Statistics and Data Management Center (SDMC), and Hongli Li, MS, also at Fred Hutch and the SWOG SDMC.
It showed that, with a median follow-up time of 15.5 years after a patient had begun treatment, the rate of disease relapse dropped substantially over time, falling from 6.8% of patients relapsing in the first 5 years to only 0.6% relapsing between years 15 and 20.
Fifteen years after starting treatment, about 70%of patients remained alive. The analysis also showed no statistically significant difference between the two treatment arms in the rates of 15-year overall survival.
Based on their work, the authors conclude that a substantial subset of patients with advanced-stage follicular lymphoma can, when treated with a standard regimen that includes immunotherapy and chemotherapy, achieve a functional cure – defined as having no chance of lymphoma recurring during the patient’s expected lifespan.
“These results reinforce that front-line chemoimmunotherapy remains an important option – particularly for appropriate patients – because it can deliver long-term disease control after a time-limited course of treatment, ” said first author Mazyar Shadman, MD, MPH, of Fred Hutch Cancer Center. Shadman is medical director of cellular immunotherapy at Fred Hutch, where he holds the Innovators Network Endowed Chair.
“As we bring novel agents into the first-line setting, the durability seen here sets a high benchmark; new strategies should aim not only to improve short-term response rates but to match or exceed long-term remission and cure potential.”
The idea that many of these patients can be cured could change how newly diagnosed patients are counseled and could eliminate the need for indefinite oncology and radiologic follow-up visits after treatment, with patients eventually transitioning from oncology care back to a primary care team.
A major new study, led by Queen Mary University of London and funded by the National Institute for Health and Care Research (NIHR) has been published in The Lancet Public Health. It found that out of the five million surgical procedures performed each year by the NHS, around 300 000 are carried out on individuals considered high-risk, and within 90 days of surgery, these high-risk patients account for:
four out of five deaths
over half of all hospital bed days
nearly one-third of emergency readmissions
While surgery is safer than ever for most people and remains the best treatment option for many conditions, this study highlights the urgent need to identify high-risk patients earlier, to provide care that is better tailored to their individual needs, and for doctors and patients to have more open, honest conversations about the risks and long-term outcomes for surgery at an individual level.
It also shows that high-risk patients, who tend to be older and live with several long-term health conditions such as heart disease, have poor outcomes not because of technical failings in surgery or anaesthesia, but due to post-operative complications relating to chronic health conditions, age and frailty. Therefore, the findings demonstrate the need for greater investment in specialist perioperative services that focus on the care of older, high-risk patients before, during and after surgery.
Rupert Pearse, Professor and Consultant in Intensive Care Medicine at Queen Mary University of London and Barts Health NHS Trust, and co-lead of the study said: “While surgery is safer than ever before, our findings clearly show that high-risk patients are more likely to have poor outcomes and experience harm after surgery than those deemed low-risk.
“Although these patients make up fewer than one in ten surgical cases, their numbers are increasing as the population ages and more people live longer with chronic illness. It is therefore vital that we work to improve care for this group of patients, pre- and post-surgery, including having open conversations with patients about the individual risk of their procedure.”
He continues: “For many years, surgical success has often been judged by survival at thirty days. Our study shows that this measure does not give the full picture of what happens to many high-risk patients in the months and years after surgery. By looking at longer-term survival and other factors such as time spent in hospital and quality of life, we could make a real difference to patients and potentially help relieve pressure on the wider NHS.”
The study is one of the largest analyses of surgical outcomes ever carried out in the UK. It analysed health records from 13 million adults who had 16.1 million surgical procedures in England, Scotland and Wales between 2015 and 2019.
Mark Bishop, Deputy Chairperson of the Hospital Association of South Africa (HASA) and Chief Commercial Officer at Lenmed Health Group, is a prominent voice in South Africa’s private healthcare sector. With more than three decades of experience, he brings deep insight into hospital management, healthcare systems and patient-centred care. Known for his strategic leadership and operational expertise, Bishop has played a key role in driving sustainable growth and innovation within Lenmed and the broader healthcare industry.
In this Q&A, Mark shares his perspectives on HASA’s role, sector priorities and the future of healthcare in South Africa.
Q: As HASA Deputy Chairperson, what do you see as the organisation’s core contribution to strengthening South Africa’s health system?
A: The private hospital sector plays a vital role by providing essential facilities and capacity for healthcare professionals to deliver quality care. Over the past four decades, private hospitals have expanded bed capacity while public sector capacity has not kept pace with population growth. This helps meet rising demand and relieves pressure on an already overburdened public system. All industry players, providers and funders, will need to consider the best collaborative approach, and the impact this would have for all and not just concentrate on the impact on their own organisations.
Q: What are HASA’s priorities for long-term sustainability of the healthcare sector?
A: Sustainability depends on affordability across both public and private healthcare. Cost drivers are the same, staffing, infrastructure and medical equipment. Improving the utilisation of limited resources across the system is critical to meeting growing healthcare needs.
Q: How do you view the current medical schemes landscape?
A: Medical schemes operate in a challenging environment characterised by stagnant membership, an ageing population, increasing chronic disease and rising costs driven by advances in medical technology. This is a consequence of a raft of incomplete reforms over the years that together have placed a heavy burden on medical scheme members. Rectifying this could take considerable expense off them.
Q: What reforms could improve affordability while maintaining quality?
A: Increasing medical scheme membership would reduce unit costs. Mandatory medical scheme covers for employed individuals, as recommended by, would expand access to care, reduces pressure on public hospitals and support progress towards universal healthcare. This would need to be done with changes to the reimbursement processes for private care, reducing the impact of fee for service and aligning with quality improvements.
Q: Your career spans 30+ years in private healthcare. What have been the most significant shifts?
Over the years, we have seen patients become more informed about their healthcare needs, medical scheme requirements have evolved and the private healthcare landscape change significantly through consolidation in medical aids.
Q: Where do you see the greatest opportunities for collaboration?
A: The private sector has spare capacity that could be used to treat publicly funded patients. Public-private partnerships, shared infrastructure and co-located facilities offer opportunities to reduce waiting times, lower costs and improve access to care. The caution, is that this needs to align with a national strategy to increase the rate at which nurses are trained, the reality is that both public and private sectors struggle to do the limited professional nurse resources.
Q: What motivates you about your role at Lenmed?
A: Lenmed’s vision of building healthier, more prosperous communities resonates with me. Our hospitals maintain a strong community focus, rooted in the founding of Lenmed Ahmed Kathrada Private Hospital over 40 years ago. Private healthcare is at a tipping point and collaboration across the sector will be essential to grow access and create a sustainable, high-quality healthcare system.
Dr Sheetal Kassim, the site lead for the Desmond Tutu Health Foundation’s clinical trial site at Groote Schuur Hospital. (Photo: Nasief Manie/Spotlight)
By Elri Voigt
A cutting-edge, South African-led HIV vaccine trial built on decades of research recently kicked off in Cape Town. Spotlight unpacks what exactly is being studied, and how the resilience, tenacity and urgency of a group of dedicated South African researchers made it possible.
Antiretroviral medicines can suppress HIV in the body and keep people healthy, but we do not yet have a viable cure for HIV or an effective vaccine. It is not for lack of trying. For decades now, researchers across the globe have been working hard to develop a vaccine against HIV. While there have been several major disappointments along the way with vaccines failing in large studies, a new clinical trial in South Africa might soon find vital answers that could reinvigorate the field.
The study was originally set to start in 2025, but researchers had to pivot and find new funders when the United States abruptly terminated much of its international research funding. After some scrambling, a stripped-down version of the study has now started. Rather than being cowed by having to delay, and reduce the size of the study, it seems that forging ahead without US support have sparked a pervasive sense of optimism.
“It feels like the most coherent, involved clinical trial I’ve ever been involved in – so that’s why I’m so excited. I feel like it’s going to lead to big things because it’s bringing so many people with it,” says Professor Penny Moore, a leading virologist who is heading up the laboratory work for the study.
That optimism is tangible at the clinical trial site in the Old Main Building at Groote Schuur Hospital in Cape Town. During our visit, one can’t help noticing how the Desmond Tutu Health Foundation’s signature rainbow logo and colourful walls and furniture breaks through the dark hospital corridors and ancient elevators.
The colourful waiting room at the Desmond Tutu Health Foundation’s clinical research site at Groote Schuur Hospital where a South African led HIV vaccine trial is taking place. (Photo: Nasief Manie/Spotlight)
Like the sugar coating on a Smartie
In the clinical trial, called BRILLIANT 011, researchers are testing two immunogens, says Dr Sheetal Kassim. She is the site lead for the Desmond Tutu Health Foundation’s clinical trial site at Groote Schuur Hospital and Principal Investigator for the trial. An immunogen is an engineered agent designed in a laboratory, she explains, to cause a specific immune response. The aim of this trial, Kassim says, is to see if these two immunogens are able to trigger the development of cells that have the potential to later become special immune cells called broadly neutralising antibodies.
Once HIV is in someone’s body, it is able to stick around mainly by taking over immune cells called CD4 cells. It evades the immune system by constantly mutating so the antibodies sent to find it don’t recognise it. Eventually the infected CD4 cells burst and die, but HIV keeps replicating, weakening the immune system.
Broadly neutralising antibodies are special antibodies that can recognise and fight a range of different HIV strains, no matter how much it has mutated, says Moore.
HIV is covered in something called glycans that make it hard for antibodies to reach it, she explains. Think of these glycans as the hard sugar coating around a Smartie. A broadly neutralising antibody can recognise the parts of the virus that won’t change when it mutates. This allows the broadly neutralising antibody to be able to reach through that hard outer coating, bind to the virus and destroy it.
Two immunogens, given at the same time
In late January, the researchers enrolled the first of an expected 20 healthy participants, who do not have HIV, and are at a low risk for getting HIV. By mid-February, seven participants had received their first shots.
It is a phase one study, which is to say it is still very early days. A phase one trial looks at the safety of a drug or vaccine in a small number of individuals, while a phase two trial looks at safety in slightly larger groups and gives some early indication of efficacy. A phase three trial is much larger and looks mainly at efficacy.
The researchers are testing the immunogenicity – essentially the ability to elicit an immune response against HIV – and safety of the two immunogens in humans for the first time. A special adjuvant – known as SMNP – is being added to the agents to enhance their effect.
The hope is that the study results will help identify a potential vaccine candidate to test in future, larger studies, says Kassim. “We’re not going to come out of this study and say we have a vaccine that can prevent or cure HIV,” she says. “But we will have information on these immunogens that will help us in the future.”
It has already been shown that the two immunogens can target the type of antibody cells that have the potential to become broadly neutralising antibodies and essentially switch them on. Think of it as a talent finding agency, says Kassim, that can find the next “star” that can become an important broadly neutralising antibody.
The two shots are injected into the muscle of the arm on three separate visits, she says. The first is given after a rigorous health screening. The second is given one month later and the final dose is given three months later. Doing it this way, primes the immune system with the first shots and then the doses that follow boost the initial effects.
Putting ‘the puzzle pieces together’
Research studies like this one is still in the “experimental medicine” phase, Professor Linda-Gail Bekker, CEO of the Desmond Tutu Health Foundation, tells Spotlight. She says results from this study will help “put the puzzle pieces together” to get a clearer picture of which immunogens should eventually be tested in a phase three efficacy trial.
The trial is novel because of the use of two immunogens instead of one. Professor Glenda Gray, Chief Scientific Officer at the South African Medical Research Council (SAMRC), refers to it as an “ambitious and aggressive approach”. She tells Spotlight that usually researchers follow a sequential pattern, testing one immunogen, then another and eventually testing them together. The problem with this is that if they don’t work together, you’ve lost up to five years of research.
“We also have this philosophy of ‘failing fast’,” Gray says. “[I]nstead of wasting money and time and effort, we need to know whether our strategy is going to work or not in the beginning.”
A proudly South Africa trial
Beyond the cutting-edge science, it’s clear that what makes this trial so unique is the people involved.
Bekker describes the trial as “proudly South African”. She says: “It’s just terrific that we’re doing this end-to-end. We’re involving the community, the recruiters are people from the country, the people who are taking the blood are people from the country, the people who are doing the laboratory science are from the country, and we’re doing it for people in our country.”
Moore adds: “We’ve got so many people in the background working on these trials at the clinical sites and here in my lab…There’s this huge mass of people all working together on this trial.”
BRILLIANT 011 is one of 22 trials currently running at the Groote Schuur Hospital site, Henriette Kyepa the Unit Manager for the site, tells Spotlight. The doors open at 07:00 and the last participant leaves by 15:00, and since at least 40 participants are being seen each day, she describes the goings on as “bustling”.
The hospital has an illustrious medical history, with the first human heart transplant having been performed in the Old Main building – the Christiaan Barnard Heart Museum is just a few floors down. The Desmond Tutu Foundation’s research site has been operating at the hospital for more than 10 years.
During a tour of the unit, Spotlight was led through a waiting area, pharmacy, and two nursing areas – where patient’s vitals are checked and data captured. Staff manning the different stations were busy, but friendly and took requests for photographs in their stride. There are four doctors’ rooms and a procedure room, equipped with things like a crash cart in case anyone has a bad reaction to a drug or device that’s being tested. The site also includes private counselling rooms and a purple, gender inclusive bathroom. Down the hall, there is a hospital ward and a small laboratory, which is shared with the University of Cape Town Clinical Research Unit, for patients that need timed blood draws for studies where drug levels are being monitored.
But before they come to the site, the first point of contact for many potential trial participants – for BRILLIANT 011 and other studies – are the community recruiters. This is a team of three outreach workers led by Amelia Mfiki, who is the community liaison officer for the Desmond Tutu Health Foundation and lead recruiter. Their job is to keep the local communities updated on what the site is doing, get their feedback and to find participants who fit the eligibility criteria for different studies.
If someone is interested in a study, Mfiki explains, they are sent to the site for an information session, where the trial, eligibility criteria and the commitment required to participate is clearly unpacked. If they meet the criteria and want to participate, they go through a further informed consent process and screening. With a big smile, she tells Spotlight there has been a lot of requests for information about the BRILLIANT 011 trial.
Once enrolled, clinical trial participants will spend a lot of time with the nursing staff. Among them is Viwe Soko, a senior nurse who says “making people smile” is part of his job.
How they’ll test if it works
The BRILLIANT 011 trial participants will need to come back roughly two weeks after each jab to have white blood cells – which contain the cells that can become broadly neutralising antibodies – extracted from their blood through a process called leukapheresis. This is how the researchers are looking for those “star” antibodies that have the potential to become broadly neutralising antibodies.
Basically, the leukapheresis machine draws a participant’s blood and runs it through a centrifuge that separates the white blood cells from all the other cells in the blood, explains Moore. The white blood cells are collected into a sterile blood bag, while the rest of the blood goes back into the participant. (Here’s a useful video showing how it works).
Hundreds of millions of white blood cells are collected each time a participant goes through this process, according to Moore. “The reason we need a crazy number [of cells] is because the responses that we’re looking for are rare as hen’s teeth,” she says.
The cells are then processed in the laboratory at Groote Schuur Hospital and sorted into different tubes containing 20, 50 and 100 million cells respectively, frozen, and then sent more than 1 000 km away to Moore’s laboratory at Wits University in Johannesburg.
Once there, the thawed antibodies are run through a special machine called a flow cytometer, which is able to spit out individual cells of interest via an ultra-thin stream. The cells are mixed with a dye to make them easy to spot, says Moore. Then a laser and computer, under the supervision of a highly trained scientist sorts the cells to isolate the types of antibodies they’re interested in.
These precursors of the broadly neutralising antibodies are “structurally weird”, said Moore, some of them have really long “arms” that can reach through HIV’s hard outer coating, or really short “arms” to get close to it.
At the end of the process, there might be 100 relevant cells which then go through a process called next generation sequencing. The researchers are looking for two specific genetic signatures that will show that the right antibody was produced. Moore likens this to a cell that has “a purple head and an orange arm” and is extremely rare. Once they find all the cells with these signatures, they count them.
At its core, Moore says, they’ll know the immunogens have worked if they find more “cells with purple heads and orange arms” than has been seen in other vaccine trials that only used one immunogen.
“I think this is some of the most important work I’ll ever do,” Moore says. “It feels like 20 years of basic science has finally paid off.”
She has been monitoring the antibody responses for the CAPRISA 002 cohort for the last two decades. It is within this cohort, that a handful of women living with HIV who had naturally produced broadly neutralising antibodies were discovered and since studied. This is part of the foundation on which the BRILLIANT 011 trial has been built.
Because of all the lab work and specialised equipment required, this kind of study is expensive to run. For the study period, it costs about R1 million for each participant to be in the trial, according to Gray. This trial has a budget of R25 million, the bulk of which has been supplied by the Gates Foundation. Some emergency funding from the SAMRC was used to make up the rest.
‘Nobody gets the urgency’ like South Africa
This amount is a far cry from the five-year USAID grant worth over $45 million, that was originally awarded to the BRILLIANT Consortium in 2023. This ambitious African-led Consortium, led by Gray and run out of the SAMRC, had big plans for HIV vaccine research and capacity development across Sub-Saharan Africa. As Spotlight previously reported, the Consortium planned to conduct three HIV vaccine trials, about one a year, and develop laboratory capacity for this kind of research across the African continent.
In the end, they only had the USAID grant for a year, just enough time to set everything up for BRILLIANT 001, a much flashier version of the trial that is currently running. It was set to take place at sites in Uganda, Kenya, Zimbabwe, South Africa and Nigeria, and recruit 60 participants, according to Gray.
“We were actually due to start it [BRILLIANT 001] in February of 2025. And then it was stopped,” Bekker says. “And so, we went through the five stages of grief and finally got to the point of acceptance. And with acceptance came a real sort of verve to try and find alternative funding.”
Essentially, the researchers were racing against the clock on multiple fronts.
The immunogens, which had been donated by labs in the Netherlands and the United States were already in the country and had expiration dates that meant the study could not be delayed indefinitely (in the end the study would start in time for this to no longer to be a concern).
But more importantly there was the roughly eight million people living with HIV in the country.
“I think nobody gets the urgency like a South African,” Bekker says. “It’s very real in our lives that this virus continues to devastate [and] change the lives of people we love and serve and work with. So that sense of urgency is very real within us.”
The team wrote up a new funding proposal and study protocol, which Bekker describes as a much lighter version, “pared down to the absolute bones”. They presented this to the Gates Foundation, which agreed to provide funding for this leaner version, and the team pushed to get everything else in place.
Gray weighs in on how, just as the process was taking off again and the protocol had been submitted to the South African Health Products Regulatory Authority (SAHPRA), which has to review and approve all clinical trials conducted in the country, the adjuvant they had planned to use was recalled by the manufacturer. Luckily, they had had some warning this might happen and had a protocol using another adjuvant ready to go. And just a year after the original trial was meant to start, they were able to kick off BRILLIANT 011.
“No one works in these timelines,” says Gray, adding that part of the reason they were able to pull this off was because of how well the team works together. “Everyone puts in more than their pound of flesh, they work incredibly hard…everyone believes in the kind of programme that we’re trying to put together,” she adds.
‘I want to help my community’
Participants for the 011 trial are reimbursed for their time and travel using a SAHPRA approved model. However, Kassim says there appears to be a more altruistic motive among participants, with some sharing sentiments like: “I want to help people. I want to help my community.”
Bekker notes a similar theme that’s held true over the last two decades of HIV vaccine research. “It’s incredibly encouraging, but it’s also incredibly humbling that, in a country like ours, where people have so many other challenges, that they could … [have] an entirely altruistic motivation, that they are digging deep within themselves and saying: ‘I’m motivated because I want to see an end to the suffering’.”
“If we truly want to bring this epidemic to an end and eliminate transmission, we will need a vaccine,” says Bekker. “And imagine, a world where you could get your vaccination, at age 10 or even younger, and then not have to think about HIV ever again.”
Disclosure: The Gates Foundation is mentioned in this article. Spotlight receives funding from the Gates Foundation but is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.
Houston Methodist researchers find antibiotics aid recovery from traumatic brain injury
Source: CC0
What if healing the brain after traumatic injury starts in the gut? In a new study published in Nature Communications Biology, Houston Methodist researchers led by Sonia Villapol, PhD, found that short-term antibiotic treatment significantly reduced neuroinflammation and neurodegeneration following traumatic brain injury (TBI) by altering the gut microbiome in animal models.
“We found that antibiotic treatment following TBI can reduce harmful gut bacteria, decrease lesion size and limit cell death,” said Villapol, an associate professor in the Department of Neurosurgery at Houston Methodist. “Our results support a gut–brain mechanism in which microbiome changes influence peripheral immunity and, in turn, neuroinflammation after TBI.¨
Administering antibiotics cleans the gut of harmful bacteria, allowing beneficial bacteria to flourish. The study found that two helpful bacteria, Parasutterella excrementihominis and Lactobacillus johnsonii, are key to driving cell repair. According to Villapol, they could also be major regulators for peripheral inflammation in the body.
Notably, 70% of immune system regulation is generated by the gut microbiome. During gut imbalance, the bidirectional nature of the brain-gut axis can wreak havoc throughout the entire body.
“Our brains are constantly sending signals to the rest of our bodies. Following a traumatic brain event, those signals can get scrambled and disrupt other organs, including our digestive system,” Villapol said. “If the gut stays out of balance, the brain may have a harder time healing.”
Recent studies indicate that TBI-induced gut microbiome imbalance may even contribute to the development of neurodegenerative diseases like Parkinson’s, Alzheimer’s and dementia.
Villapol’s lab is focused on investigating and developing new neuroprotective treatments to fight inflammation linked with neurodegenerative disease. “If we can break neuroinflammation in the acute or chronic stage, we can reduce the risk of developing Alzheimer’s or dementia,” said Villapol.
The next phase of the research will focus on bioengineering P. excrementihominis and L. johnsonii to further develop precision therapies to reduce neuroinflammation.
Findings could help patients avoid side significant effects and improve quality of life
Credit: Darryl Leja National Human Genome Research Institute National Institutes Of Health
A new study led by UCLA Health investigators suggests that adding hormone therapy to post-operative radiotherapy may provide little survival benefit for most men with prostate cancer, especially for those with very low PSA levels before treatment.
The researchers found that for men with low PSA levels prior to radiotherapy, adding hormone therapy, whether short-term or long-term, did not improve overall survival. Men with higher PSA levels before radiation may see modest improvements in survival and metastasis-free survival, suggesting hormone therapy may be beneficial primarily for this higher-risk group.
The results were published in The Lancet and presented by Dr Amar Kishan, professor and executive vice chair of radiation oncology at the David Geffen School of Medicine at UCLA, during the plenary session of the American Society of Clinical Oncology Genitourinary Cancers Symposiumin San Francisco.
“Hormone therapy, which impacts the ability of testosterone to stimulate prostate cancer growth and repair, has been shown to improve outcomes when combined with radiotherapy in men whose prostates are still intact. However, whether it has a similar benefit for men receiving radiotherapy after prior surgery has remained unclear,” said Kishan, first author of the study and co-director of the cancer molecular imaging, nanotechnology and theranostics program at the UCLA Health Jonsson Comprehensive Cancer Center. “At the same time, hormone therapy carries significant side effects, including severe fatigue, hot flashes, sexual dysfunction, weight gain, bone loss and metabolic changes that can increase cardiovascular risk. Our findings show that for most men with detectable but low PSA levels (<0.5 ng/mL), after surgery to remove the prostate, post-operative radiotherapy is highly effective on its own. By safely omitting hormone therapy in these patients, we can potentially spare them months of treatment that may substantially affect their quality of life without extending survival.”
To better understand the impact of hormone therapy in this setting, the researchers conducted a large-scale, individual patient-level meta-analysis through the MARCAP Consortium, an international collaboration co-led by Kishan that is designed to evaluate long-term outcomes across randomized clinical trials.
The team analysed data from 6057 men enrolled in six randomised trials comparing post-operative radiotherapy alone to radiotherapy combined with either short-term (4-6 months) or long-term (24 months) hormone therapy. By pooling individual patient data rather than relying on summary trial results, investigators were able to examine outcomes in greater detail, including how pre-radiation PSA levels influenced treatment benefit.
Patients were followed for a median of nine years, allowing researchers to assess long-term overall survival, metastasis-free survival and recurrence outcomes. The analysis also enabled direct comparisons between short-term and long-term hormone therapy to determine whether extending treatment duration improved outcomes.
The researchers found that overall, 83.6% of men who received post-operative radiotherapy alone were alive after 10 years, compared with 84.3% for those who received post-operative radiotherapy plus hormone therapy.
Researchers found that pre-radiotherapy PSA levels, a measure of prostate-specific antigen in the blood after prostatectomy, played a crucial role. Men with low PSA levels before radiotherapy (≤0.5 ng/mL) saw no benefit from hormone therapy. In contrast, men with higher PSA levels showed modest improvements in survival, suggesting that hormone therapy may only be worthwhile for those with elevated PSA.
The study also examined the duration of hormone therapy. Short-term therapy did not improve overall survival, though it slightly reduced the risk of cancer spreading. Long-term therapy showed a small survival benefit, particularly for men with higher PSA levels after prostatectomy. However, the team’s statistical analysis demonstrated that extending short-term therapy to long-term therapy did not further improve survival, although it did modestly lower the risk of metastasis.
“Our goal is always to treat the cancer while minimizing harm,” said Kishan. “This study helps us move toward more personalised care for men with prostate cancer. By better identifying who truly benefits from hormone therapy, we can make treatment smarter, reduce unnecessary interventions and focus on improving patients’ overall well-being.”
Building on those findings, ongoing research is working to further refine that approach. Trials such as the BALANCE Trial aim to pinpoint biomarkers that can identify which men are most likely to benefit from hormone therapy after surgery, helping tailor treatment decisions even more precisely.
In a leap for personalised medicine, scientists have discovered a simple and valuable way to improve brain cancer surgeries.
Taylor Furst, MD, observes a brain mapping procedure in progress at the University of Rochester’s Strong Memorial Hospital. Credit: Matt Wittmeyer
When removing cancerous tissue in the brain, neurosurgeons often use “awake brain mapping” to minimise the risk of causing unintended disruptions to a patient’s quality of life while removing as much tumour as possible. This practice, which has been used for decades, involves waking a patient up mid-surgery to test their neurocognitive functions in real time by stimulating the brain surface and assessing for functional changes.
A new study published in the journal Science Advances details a promising new avenue toward improving awake brain mapping results by investigating the tiny, nearly imperceptible variabilities in patient behaviour that occur during the procedure. This work, led by Carnegie Mellon University researchers, points to a future where brain surgeries are not just safer, but more precisely tailored to protect each patient’s speech, movement and quality of life.
How awake brain mapping works
As cancer grows in the brain, it rarely keeps to itself. Cancerous cells can be found in the seemingly healthy brain tissue surrounding a tumour, presenting neurosurgeons with a dilemma. They need to remove as much tissue infiltrated by cancer as possible, but they also need to avoid the removal of too much tissue since it can cause permanent harm to a patient’s ability to hold a fork or a conversation.
During awake brain mapping, surgeons gently stimulate the brain with small electrical impulses while the patient completes planned tasks. One of the most common applications of awake brain mapping is to identify where language is represented in a patient’s brain, which is done by having the patient name pictures or read words while their brain is being stimulated. If the patient can respond quickly and correctly, the clinicians know the part of the brain they stimulated can be safely removed. If the patient slurs or becomes unable to speak, then that part of the brain may be essential for language. Surgeons require a significant amount of experience to understand the nuances of this complex technique.
While the method may sound extreme, the brain has no sensory nerves, so patients do not feel their brain surgery as it is happening. Recent research also shows that for some types of brain cancer, improving a patient’s quality of life after surgery extends their expected survival into the future. This means that anything that can make awake brain mapping even more effective will translate into improved outcomes for brain cancer patients.
New measures show how slight changes in procedure affect patient behaviour
Based on a decade of research, the study authors uncovered new insights from examining the answers patients get wrong – and right – while undergoing awake brain mapping.
“We found that if you measure both the types of errors that patients make, as well as how fast they respond even when they do not make errors, more granular inferences can be drawn about language organization from an awake brain mapping procedure,” said Bradford Mahon, a cognitive neuroscientist at CMU’s Neuroscience Institute and Department of Psychology and senior author of the study. “We also found that physical parameters of the direct electrical stimulation delivered to the patient’s brain – such as its duration, and when it started and stopped relative to the task the patient is performing – were tightly related to small changes in patient behaviour that we could measure.”
Mahon and his team don’t yet know exactly what combination of parameters should be used to maximise the effect of direct electrical stimulation mapping. But they have discovered an intriguing signal hidden inside of the data that, until now, has gone unnoticed.
“What we have measured and formalised in our study is how slight changes in the awake mapping procedure can cause slight changes in patient behaviour. This is exciting because it is a new and meaningful signal that can be extracted from the data already being generated during awake brain mapping procedures,” said Mahon.
A new level of personalised medicine
The new study suggests that awake brain mapping may offer more informative and more personalized guidance for surgery than has been possible in the past.
For example, stimulating a particular area of the brain might reliably cause an error, never affect behaviour at all, or – more subtly – slow a patient’s response without causing an obvious mistake. In some cases, stimulation may affect behaviour at one moment, but not when tested again just seconds later.
“In other words, brain mapping isn’t always black or white,” said Belkhir. “Sometimes the most important information lives in the grey area.”
The nuance matters because every brain is different, which means every surgery is different, too. Understanding why stimulation has variable effects across different patients, and even within the same patient from one part of the surgery to another part of the surgery, may be key to protecting outcomes for future patients.
“Surgeons are seeking to optimise the balance between removing all of the cancerous tissue while preserving critical functions that may be represented by nearby brain regions,” said Mahon. “This research shows that by measuring aspects of patient performance that were previously not considered relevant for awake brain mapping, even better predictive models of brain organisation can be developed.”
If clinical teams have better predictive models personalised to each patient, then the consequences of different surgical approaches on postoperative neurocognitive function can be simulated. This allows for patients and their caregivers to personalise decisions to what is most important to the patient.
In other words, Mahon said, a business manager may consent to a surgery that may diminish their motor skills, but not their speech, whereas a concert violinist may prefer the opposite.
Bringing standardisation to awake brain mapping surgery
Another important development from this research is the startup company MindTrace, which has built an integrated software platform that supports neurocognitive testing before, during and after surgery. It is working to build a longitudinal dataset of patient outcomes that will be used to train forecasting models.
Tyler Schmidt, MD, study co-author and neurosurgeon at the University of Rochester, has used MindTrace in over a dozen awake surgeries since its release this year.
“In the beginning of brain tumour surgery, it used to be, ‘Can we remove any of this tumour safely?’” said Schmidt. ”But now in some brain tumour cases it’s, ‘Can we get you back to work potentially? Can we keep your quality of life close to what it was prior to your diagnosis? Can we hone in on the things that are most important to you and then try and protect them while getting the same oncological outcome?’” said Schmidt. “I think it’s a positive paradigm shift in how we take care of this patient population.”
The options today are measurably better than they were even 20 years ago. Clinicians now understand how to maximise the likelihood that patients have the best possible outcomes from brain cancer surgery.
“Ultimately, we are contributing toward the set of tools that clinicians will have that will enable them to map the brain with even greater confidence and precision, and personalised to each patient,” said Mahon. “The big goal is to translate scientific insights into solutions that improve people’s lives. We will meet that goal by building tools that enable the best possible outcomes in neurosurgery patients, both in terms of neurocognitive function and quality of life, and ultimately, in terms of survival.”
