Associate Professor Angelique Kany Kany Luabeya speaks about TB vaccine trials and the introduction of TB vaccines in South Africa. (Photo: Supplied)
By Angelique Kany Kany Luabeya
The only tuberculosis vaccine we have is a century old and offers only limited efficacy in children. With leading South African researchers involved in the pivotal clinical trials of three new tuberculosis vaccine candidates, we are on the verge of a major breakthrough, writes Associate Professor Angelique Kany Kany Luabeya.
My uncle died of abdominal TB a few days ago, after facing repeated challenges in getting an accurate diagnosis. For him, the treatment started much too late. To many in his community, my uncle was a respected teacher, a breadwinner, a pillar of support and strength.
In 2026, why are people still dying from a preventable disease that continues to cause unnecessary deaths and hardship?
Why we urgently need a new TB vaccine should be obvious. For the millions who are sick, and for families living with the catastrophic loss of a loved one, the need is painfully clear.
Prior to the emergence of the SARS-CoV-2 virus, TB was the world’s deadliest infectious disease, killing more than 1.5 million people every year. While COVID-19 has since shown an epidemic downturn, TB’s toll remains devastatingly high.
Globally, an estimated 2 billion people are infected with the Mycobacterium tuberculosis that causes TB in humans. In this state, also known as latent TB infection, they do not have TB symptoms and are non-infectious, but the bacteria remain dormant in their bodies. Of these people, about 5 to 10% will go on to develop active TB when their immune system is no longer able to contain the bacteria. This means that they now have TB disease, sometimes without noticeable symptoms, and risks passing it to others. This could be a family member, a friend, or a stranger who happens to be nearby.
TB bacteria have coexisted with humans for millions of years. There is a cure, but treatment alone is not enough to stop transmission. TB mostly affects countries with limited resources because patients struggle to access care or are unable to complete treatment due to side effects or a lack of food to support the rigorous regimen of drugs they must take to cure them. In addition, the rise of multidrug-resistant tuberculosis is now fueling a global health crisis.
In South Africa, recent data from the World Health Organization’s (WHO) Global TB Report indicate progress, with a 57% reduction in new TB cases since 2015. However, TB mortality is still high and is concentrated mainly in poor and vulnerable communities. According to the WHO, TB still claims over 50 000 lives in South Africa every year. The burden is also unevenly distributed, with some geographic areas affected more than others.
A vaccine which prevents TB
Our hopes are now pinned on developing an efficacious vaccine which prevents people from developing TB disease. WHO modelling suggests that a vaccine which prevents most people with latent TB infection from progressing to active disease would have the most rapid impact on the epidemic in high‑burden countries.
The most urgent priorities for protection would be people living with HIV, healthcare workers at risk of workplace exposure, adolescents and young adults who are driving transmission, as well as those with comorbidities such as diabetes that increase their risk of TB diseases and negatively affect treatment outcomes.
The COVID-19 pandemic proved that when human survival is threatened, the scientific community can respond with breathtaking speed, developing multiple effective vaccines in under a year. Sadly, the urgency and resources allocated to finding an effective TB vaccine do not match the scale of its devastation.
For more than a century (since 1921), we have had only one licensed TB jab, which is the bacillus Calmette-Guérin (BCG) vaccine that is given at birth. Despite its limitations in preventing TB that infects the lungs – the main route of transmission – BCG remains a critical tool because it protects millions of babies from more serious forms of TB that can spread through the blood to the brain. But, clearly, the BCG vaccine is not enough.
Hope is on the horizon though, with several novel TB vaccines now in late-stage clinical trials. New vaccines or drugs are evaluated clinically in humans in steps, or phases, for safety, immunogenicity, and efficacy.
The most advanced is M72/AS01E (M72 for short), which is an adjuvanted subunit vaccine under development by the Gates Medical Research Institute and GlaxoSmithKline. In a phase 2 trial, this vaccine showed close to 50% efficacy in preventing TB disease in TB-infected people—the first time a vaccine has achieved this level of efficacy. A pivotal phase 3 trial of this vaccine has now completed enrolment of 20 000 volunteers, including 13 000 people in South Africa, with results expected in 2028. Developers typically apply for registration with regulatory authorities after successful phase 3 trials – so this study is the last big hurdle for this vaccine.
Another promising candidate is the MTBVAC vaccine, a live, whole, attenuated Mycobacterium tuberculosis vaccine developed by Biofabri, in partnership with the University of Zaragoza and sponsored by the International AIDS Vaccine Initiative. It is in a multi-country phase 2b trial in adults and adolescents and a phase 3 trial in newborns, including in South Africa.
BioNTech’s mRNA TB vaccine is also being evaluated in a phase 2a study in South Africa. Funded by BioNTech, this vaccine candidate harnesses mRNA technology, which has proved successful in the COVID-19 response.
Paving the way for acceptance and use
South African researchers are at the forefront of these TB vaccine efforts. Our strengths lie in our robust clinical trial capacity, world-class institutions, commitment to equitable solutions, and regulatory expertise, all of which help accelerate vaccine licensure. As a global policy leader, South Africa co-chairs the Finance and Access Working Group at the WHO TB Vaccine Accelerator Council, advocating for fair distribution and sustainable financing, and has recently co-hosted a vaccine preparedness workshop to position the country for the emergence of late-stage TB vaccines.
But the most important aspect to consider is the vaccine’s acceptability and uptake by a myriad of population groups at risk of TB. We learned from COVID-19 how misinformation can devastate vaccine uptake, leading to unnecessary morbidity and mortality. Confidence in new TB vaccines must be built to maximise impact. The context may be different—TB is an old, well-known enemy that affects people close to us. By involving South African communities in the early stages of vaccine trials, we can ensure their priorities are part of the development agenda.
While we continue to improve TB diagnosis and treatment, the hunt for an effective vaccine continues. After a century of fighting TB with only one vaccine and several antibiotics, we might be on the verge of a breakthrough that could finally shift the trajectory of this ancient and deadly disease.
*Associate Professor Angelique Kany Kany Luabeya is the clinical investigator on the M72 TB vaccine trials being conducted at the South African Tuberculosis Vaccine Initiative based at the University of Cape Town.
Disclosure: The Gates Medical Research Institute mentioned in this article is a non-profit organisation and subsidiary of the Gates Foundation. 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.
Note: Spotlight aims to deepen public understanding of important health issues by publishing a variety of views on its opinion pages. The views expressed in this article are not necessarily shared by the Spotlight editors.
In South Africa, where the burden of HIV remains high, women living with HIV face a disproportionately increased risk of cervical cancer, around six times higher than women without HIV. This heightened risk is driven by persistent infection with high‑risk strains of human papillomavirus (HPV). In settings where access to HPV vaccination, cervical screening and treatment is uneven, the impact on women’s health and lives is profound.
New research published in The Lancet Global Health provides the first population‑level evidence globally that a national HPV vaccination programme can be highly effective in a high HIV‑prevalence setting. The study was led by researchers from Wits RHI at the University of the Witwatersrand in partnership with the Kirby Institute (University of New South Wales).
The study evaluated South Africa’s free, school‑based national HPV vaccination programme, introduced in 2014, which offers HPV vaccination to girls in Grade 4 (aged nine years and older) attending public schools across the country. Crucially, the research assessed vaccine impact among adolescent girls and young women both living with HIV and without HIV, reflecting the realities of South Africa’s dual HIV and cervical cancer burden.
Until now, most evidence on HPV vaccine effectiveness in people living with HIV has come from studies where vaccination occurred after HIV infection, often after exposure to HPV and in the presence of immune suppression. This South African study, led by Professor Sinead Delany-Moretlwe at Wits RHI, Director of Research, is the first to demonstrate the real‑world impact of vaccination delivered early, before most girls are exposed to HPV, within a national public‑health programme in a high HIV‑burden context.
The findings show that the HPV vaccine provides excellent protection, including among girls living with HIV. Researchers observed substantial reductions in vaccine‑type HPV infections, demonstrating that high‑coverage HPV vaccination programmes can deliver strong population‑level benefits, even in settings with widespread HIV.
“For the first time, we can demonstrate at a population level that HPV vaccination delivered early, through a national public programme, provides excellent protection in a high HIV‑prevalence setting. This is a major public‑health success for South Africa and sends a clear message globally: investing in early, school‑based HPV vaccination can dramatically reduce future cervical cancer risk, including among girls living with HIV,” said Professor Sinead Delany-Moretlwe.
These results have major global implications. They reinforce the critical importance of early, school‑based HPV vaccination and provide compelling evidence for countries, particularly those with high HIV prevalence, to implement and sustain national HPV vaccination programmes. Such programmes have the potential to dramatically reduce cervical cancer risk, improve women’s health outcomes, and ultimately save lives worldwide.
South Africa’s public tender framework has long recognised the importance of ensuring reliable, affordable, and uninterrupted access to essential medicines and vaccines, particularly for national immunisation programmes that protect children and vulnerable populations.
While local pharmaceutical manufacturing remains an important national objective, it is equally critical that public procurement decisions prioritise patient access, programme sustainability, and fiscal responsibility, especially in vaccine supply where scale, complexity, and affordability are decisive factors.
Vaccines require scale, specialisation and reliability
Vaccine manufacturing at national immunisation scale requires highly specialised infrastructure, advanced technical capability, strict regulatory compliance, and sustained capital investment. These requirements differ materially from those of many small‑molecule medicines.
“When it comes to vaccines, the overriding priority of the public tender system must be patient access. Scale, affordability, and uninterrupted supply are essential if South Africa is to expand and sustain its national immunisation programmes,” said Simo Masondo, Chairman of the Generic and Biosimilar Medicines Association of South Africa (GBMSA).
Although South Africa has made meaningful progress in strengthening elements of local pharmaceutical capability, vaccine manufacturing readiness varies significantly across product categories, and certain capacities continue to evolve. In this context, national immunisation programme must be supported by a calibrated combination of local and global manufacturing supply, particularly where programme expansion, continuity and affordability are at stake.
A tender system that prioritises supply reliability and scale is essential to ensuring that immunisation program can reach more patients, more consistently and without interruption.
Competitive pricing and demonstrable value for money remain central to the sustainability of South Africa’s public healthcare system. The National Department of Health has consistently emphasised procurement principles that include value for money, open and effective competition, accountability, and equity.
In vaccine procurement, competitive tender outcomes directly enable:
Broader immunisation coverage
Greater reach to children and underserved populations
More efficient use of limited public healthcare resources
Affordability is not a secondary consideration; it is a core enabler of access.
BRICS partnerships as strategic enablers of vaccine access
Trusted international partnerships, particularly within the BRICS ecosystem, play a critical role in supporting South Africa’s vaccine supply objectives. Long‑standing collaborations with partners in countries such as India have consistently demonstrated scale, reliability, regulatory compliance, and significant cost efficiencies in national tenders.
Indian vaccine manufacturers have historically delivered substantial savings to the South African government, in some cases exceeding R2 billion on a single vaccine programme, while supporting the expansion and sustainability of national immunisation coverage.
These partnerships should be viewed not as alternatives to local capability, but as essential enablers of immediate access, affordability, and programme continuity, particularly in vaccine categories where local scale is still developing.
A pragmatic and patient‑centric path forward
“A pragmatic, balanced approach allows South Africa to meet today’s immunisation needs while continuing to build capability over time. This is not a choice between localisation and access; it is about sequencing decisions responsibly so that patients always come first,” Masondo said.
Such an approach ensures:
Reliable and uninterrupted vaccine supply
Expanded immunisation reach for South African children
Responsible stewardship of public healthcare funds
Long‑term programme sustainability
Strengthened international cooperation within BRICS and other trusted partnerships
By prioritising access, affordability, and scale in vaccine procurement, South Africa can protect its immunisation programmes today while continuing to build manufacturing capability over time, without compromising patient outcomes or fiscal sustainability.
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.
Sanofi is pleased to share that the South African Health Products Regulatory Authority (SAHPRA) has granted registration for Beyfortus® (nirsevimab), a long-acting monoclonal antibody designed to protect infants against Respiratory Syncytial Virus (RSV).
Beyfortus® is the first long-acting monoclonal antibody designed to provide protection across the RSV season for all infants, including those born at term, preterm, or with underlying conditions. It is given as a single intramuscular dose just before or during the RSV season¹ and is expected to be available before the 2026 RSV season.
RSV is one of the leading causes of Lower Respiratory Tract Infections (LRTIs) such as bronchiolitis and pneumonia in young children, and a major driver of hospitalisation in infants under one year of age.3 Globally, RSV is responsible for 20 to 40% of pneumonia and 40 to 80% of bronchiolitis hospitalised cases among infants under one year of age.2
It was estimated that in a year, RSV caused around 33 million acute lower respiratory infections in children younger than five years, resulting in 3,6 million hospitalisations and over 100 000 RSV-attributable deaths globally3. RSV-related medical costs in this age group are estimated at €4.82 billion per year, including hospital, outpatient, and follow-up care7.
In South Africa, RSV infections occur year-round with a strong seasonality from February to May4. Each year in South Africa, there are approximately 96 000 cases of RSV severe acute respiratory illnesses in children under five years of age, and among newborns under one month, about one in seven requires admission for severe RSV9. The incidence and severity of RSV LRTI are highest in infants under 6 months of age, representing 22% of all-cause hospital admissions in this age group. 41% of the LRTI-related hospitalisations are attributable to RSV.5
RSV infections also have long lasting consequences as a first episode of RSV LRTI is associated with an increased risk of subsequent LRTIs. In addition, RSV is associated with recurrent wheezing in early childhood.6
Though risk factors such as prematurity and underlying conditions will increase the probability and severity of RSV infections in children, the majority of severe RSV outcomes occur in healthy full‑term infants. They represent the majority of ICU admissions (65.8%) and mechanical ventilation cases (59.8%) among RSV‑infected infants, and globally, healthy infants account for around 57% of RSV‑related deaths.10-11 For this reason, all infants are at risk of RSV disease.
A single dose of Beyfortus® provides immediate and season-long protection, lasting for at least five months, corresponding to a typical RSV season¹. In the MELODY phase III trial*, nirsevimab reduced medically attended RSV-LRTI by 74.5% and hospitalisations by 62.1% compared with placebo,8 while the HARMONIE real-world study found an 82.7% reduction in RSV-related hospitalisations through 180 days after immunisation14. Beyfortus® demonstrated a consistent safety profile across term, preterm, and high-risk infants, with the most common adverse reactions being mild rash (0.7%), fever (0.5%), and injection-site reactions (0.3%)¹.
Beyfortus® has also demonstrated its strong public health impact in real-world settings. Following its introduction in 2024 in Chile and in 2023 in Galicia, Spain, the effectiveness of Beyfortus® against RSV-related LRTI hospitalisations was estimated to be 76.4% and 85.9%, respectively. In Chile, Beyfortus® demonstrated 49.7% effectiveness against all-cause hospitalisation. 12-13
“RSV causes a great burden on families and the healthcare systems in South Africa and worldwide,” says Diane Buron, South Africa Medical Head for Sanofi Vaccines. “It is a leading cause of infant hospitalisation during the season and Beyfortus® has the potential to change that. With only one dose, babies will be effectively protected throughout the season and thousands of cases and hospitalisations can be averted.”
“Because the majority of RSV cases are in term and healthy infants,” says Buron “proposing this innovative and effective protection to all infants will have a significant impact on the families and healthcare system.”
More than 6 million infants worldwide have now received Beyfortus®, supported by over 40 real-world studies across four continents, in both the Northern and Southern hemispheres. The introduction of Beyfortus® in South Africa is a significant advancement in paediatric respiratory protection and supports the global goal of reducing preventable infant morbidity and mortality linked to RSV8.
*The Phase 3 MELODY trial was a randomised, double-blind, placebo-controlled trial conducted across 21 countries designed to determine the safety and efficacy of Beyfortus® against medically attended LRTD caused by RSV in healthy term and late preterm infants (35 weeks gestational age or greater) entering their first RSV season, including efficacy against severe disease such as hospitalisation, through 150 days after dosing. The primary endpoint was met, reducing the incidence of medically attended RSV LRTD by 74.5% (95% CI 49.6, 87.1; P<0.001) compared to placebo. The efficacy of Beyfortus® against the secondary endpoint of hospitalization was 62.1% (-8.6, 86.8). A pre-specified pooled analysis of the Phase 3 MELODY trial showed the efficacy of Beyfortus® against medically attended RSV LRTD and medically attended RSV LRTD with hospitalisation was 79.5% (95% CI 65.9, 87.7; P<0.0001) and 77.3% (95% CI 50.3, 89.7; P<0.001), respectively.
References
1. Sanofi-Aventis South Africa (Pty) Ltd. Beyfortus® Professional Information (PI). Version E, 2025-09-18. 2. Dangor et al. (2023) – Bronchiolitis v. bronchopneumonia: Navigating antibiotic use within the lower respiratory tract infection spectrum. S Afr Med J 113(6):e709
3. Li Y et al. Global, regional, and national disease burden estimates of acute lower-respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis. Lancet. 2022; 399: 92047–64. 4. National Institute for Communicable Diseases (NICD). Respiratory Syncytial Virus (RSV). Available at: https://www.nicd.ac.za/diseases-a-z-index/respiratory-syncytial-virus-rsv/ (Accessed January 2026). 5. Wedderburn CJ et al. Risk and rates of hospitalisation in young children: A prospective study of a South African birth cohort. PLOS Glob Public Health. 2024
6. Zar HJ et al. Early-life respiratory syncytial virus lower respiratory tract infection in a South African birth cohort: epidemiology and effect on lung health. Lancet Glob Health. 2020. 7. Zhang S et al. Cost of respiratory syncytial virus-associated acute lower-respiratory infection management in young children at the regional and global level: a systematic review and meta-analysis.J Infect Dis. 2020; 222(Suppl 7): S680–S687. 8. Hammitt LL et al. Nirsevimab for prevention of RSV in healthy late-preterm and term infants.N Engl J Med. 2022; 386(9): 837–846.
9. Moyes J et al. The burden of RSV-associated illness in children aged < 5 years, South Africa, 2011 to 2016. BMC Med 21, 139 (2023).
10. Nair H, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010;375:1545–1555. 11. Li Y, et al. Global, regional, and national disease burden estimates of RSV-associated acute lower respiratory infection in young children in 2019: a systematic analysis. Lancet. 2022;399:2047–2064
12. Razzini JL. Impact of universal nirsevimab prophylaxis in infants on hospital and primary care outcomes across two respiratory syncytial virus seasons in Galicia, Spain (NIRSE-GAL): a population-based prospective observational study. Lancet Infect Dis. 2026
13. Torres JP et al. Effectiveness and impact of nirsevimab in Chile during the first season of a national immunisation strategy against RSV (NIRSE-CL): a retrospective observational study. Lancet Infect Dis. 2025 Nov;25(11):1189-1198.
14. Munro et al. 180-day efficacy of nirsevimab against hospitalisation for respiratory syncytial virus lower respiratory tract infections in infants (HARMONIE): a randomised, controlled, phase 3b trial. Lancet Child Adolesc Health. 2025 Jun;9(6):404-412.
New research reveals that activating the brain’s reward system through positive anticipation strengthens the immune response and increases antibody production
Can positive anticipation that activates the brain’s reward system strengthen the body’s immune defences? A new study by Tel Aviv University, the Technion, and Tel Aviv Medical Center (Ichilov), published in the prestigious journal Nature Medicine, provides the first evidence in humans that brain activity associated with the expectation of reward has a measurable effect on the body’s response to a specific vaccine.
Eighty-five healthy volunteers participated in the experiment. Some underwent special brain training using fMRI neurofeedback technology – a method that enables individuals to learn, in real time, to regulate activity in specific brain regions through reinforcing learning. The aim of the brain training was to increase activity in a key region of the brain’s reward system including the Ventral Tegmental Area (VTA), which is responsible for dopamine release in the context of mental activity related to the expectation of positive outcomes and motivation to obtain rewards. Participants were instructed to modulate their brain activity using various mental strategies (eg, thoughts, feelings, memories) while monitoring positive feedback about the strategy that was successful in regulating their brain.
From Brain Activation to Antibodies
Immediately after completing the brain training, all participants received a hepatitis B vaccine. The researchers then tracked the immune response through a series of blood tests, measuring levels of specific antibodies produced following the vaccination.
The results showed that participants who succeeded in significantly increasing activity in the brain’s reward region also demonstrated a greater increase in antibody levels after vaccination. The association was specific to the VTA and was not observed in other brain regions used for control purposes (such as the hippocampus), nor in other reward-system areas linked to different reward-related experiences such as pleasure and satisfaction. In other words, the effect was both anatomically and mentally specific.
The Role of Positive Anticipation
Furthermore, an in-depth analysis of the mental strategies participants used during training of the VTA (and not other regions) revealed that those who focused on positive anticipation, such as belief in a good outcome, or the expectation of something positive about to happen, were able to maintain higher VTA brain activity over time, which was also associated with a better immune response. In other words, the researchers identified a link between reward-system brain activity, a mental state of positive anticipation, and the body’s response to an immune challenge.
According to the research team, this is not “positive thinking” in the popular sense or a New Age slogan, but a measurable neurobiological mechanism – related, among other things, to the well-known placebo effect in medicine (a therapeutic response beyond a specific medical intervention). “We show that mental states have a clear brain signature, and that this signature can influence physiological systems such as the immune system,” explain the researchers.
While the study does not propose a substitute for vaccines or medical treatment, it opens the door to new, noninvasive approaches that may one day strengthen immune responses, improve the effectiveness of medical treatments, and even contribute to fields such as immunotherapy and the treatment of chronic immune pathologies. The researchers note that the study’s findings underscore a broader message: the mind–body connection is not merely a theoretical concept, but a real biological process that can be measured, trained, and potentially harnessed to promote better health.
Implications for Medicine and Health
The research team adds that the findings highlight the potential inherent in integrating neuroscience, psychology, and medicine. “Our study shows that the brain is not only a system that responds to the body’s state of health, but also an active player that influences it,” say the researchers. “The ability to consciously activate brain mechanisms associated with positive anticipation opens a new avenue for research and future treatments – as a complement to existing medicine, not as a replacement. In the future, it may be possible to develop simple, noninvasive tools to help strengthen immune responses and enhance the effectiveness of medical treatments by relying on the brain’s natural capacity to influence the body. However, it is important to emphasise that activation of the reward system and its effect on immune response vary between individuals. Therefore, this approach cannot replace existing medical treatments, but may well serve as an additional supportive component.”
Using data from the nationally representative US Health and Retirement Study, researchers examined how shingles vaccination affected several aspects of biological aging in more than 3800 study participants who were age 70 and older in 2016. Even when controlling for other sociodemographic and health variables, those who received the shingles vaccine showed slower overall biological aging on average in comparison to unvaccinated individuals.
Shingles, also called herpes zoster, is a painful, blistering skin rash caused by the reactivation of the chickenpox virus, or varicella zoster. Anyone who has had chickenpox is at risk for shingles; while shingles can occur at younger ages, risk is higher for those 50 and older and immunocompromised individuals. Vaccination, which has generally only been provided to older people, offers protection from shingles as well as a lower chance of postherpetic neuralgia, or long-term pain after a shingles infection.
While vaccines are designed to protect against acute infection, recent research has highlighted a possible connection between adult vaccines, including those for shingles and influenza, and lower risks of dementia and other neurodegenerative disorders, said Research Associate Professor of Gerontology Jung Ki Kim, the study’s first author.
“This study adds to emerging evidence that vaccines could play a role in promoting healthy aging by modulating biological systems beyond infection prevention,” she said.
Measuring the body, not the calendar
Unlike chronological aging, biological aging refers to how the body is changing over time, including how well organs and systems are working. Two people who are both 65 years old may look very different inside: one may have the biological profile of someone younger, while another may show signs of aging earlier.
In the new study, Kim and coauthor Eileen Crimmins, USC University Professor and AARP Professor of Gerontology, measured seven aspects of biological aging:
inflammation
innate immunity
adaptive immunity
cardiovascular haemodynamics
neurodegeneration
epigenetic aging (changes in how genes are turned “off” or “on”)
transcriptomic aging (changes in how genes are transcribed into RNA used to create proteins)
The team also used the measures collectively to record a composite biological aging score.
Surprising results beyond shingles prevention
On average, vaccinated individuals had significantly lower inflammation measurements, slower epigenetic and transcriptomic aging, and lower composite biological aging scores. The results provide more insight into the possible mechanisms underlying how immune system health interacts with the aging process.
Chronic, low-level inflammation is a well-known contributor to many age-related conditions, including heart disease, frailty, and cognitive decline. This phenomenon is known as “inflammaging,” Kim said.
“By helping to reduce this background inflammation — possibly by preventing reactivation of the virus that causes shingles, the vaccine may play a role in supporting healthier aging,” she said. “While the exact biological mechanisms remain to be understood, the potential for vaccination to reduce inflammation makes it a promising addition to broader strategies aimed at promoting resilience and slowing age-related decline.”
These potential benefits could also be persistent. When analysing how the time since vaccination affected results, Kim and Crimmins found that participants who received their vaccine four or more years prior to providing their blood sample still exhibited slower epigenetic, transcriptomic and overall biological aging on average versus unvaccinated participants.
“These findings indicate that shingles vaccination influences key domains linked to the aging process,” Crimmins said. “While further research is needed to replicate and extend these findings, especially using longitudinal and experimental designs, our study adds to a growing body of work suggesting that vaccines may play a role in healthy aging strategies beyond solely preventing acute illness.”
Red blood cells and serum separate after spinning in a centrifuge in the UVM Vaccine Testing Center. (Photo: Andy Duback)
The world’s first single-dose vaccine to prevent dengue fever has been approved for licensure in one of the largest countries affected by the disease, following 16 years of research contributions by scientists at the University of Vermont (UVM) Vaccine Testing Center, in partnership with the US National Institutes of Health (NIH) and the Johns Hopkins Bloomberg School of Public Health (JHSPH).
Dengue is the most common mosquito-borne disease worldwide, with nearly half the world’s population living in places with the risk of dengue. Along with high fever and severe muscle and bone pain, the virus can lead to shock, bleeding, and death. With more than 100 million cases reported annually, dengue poses a growing risk throughout the globe. Brazil recorded 5.9 million cases of dengue and more than 6000 deaths in 2024.
The new vaccine has now been licensed for use in Brazil under the name Butantan-TV. On November 26 the Instituto Butantan, a biologic research centre in São Paulo, announced that the vaccine will be incorporated into Brazil’s national immunisation program. Additional global approvals are anticipated as the vaccine is developed through other pharmaceutical partners including Merck and the Serum Institute of India.
In addition to the vaccine approval, a promising new antiviral medication designed to prevent infection and illness in individuals exposed to dengue virus will now advance, thanks to clinical trials at the UVM Vaccine Testing Center and JHSPH. The findings were published in the November 26 issue of the New England Journal of Medicine (NEJM).
“These milestones represent a turning point in global dengue prevention and treatment,” said UVM Vaccine Testing Center founder Beth Kirkpatrick, M.D., professor and chair of the Department of Microbiology and Molecular Genetics at the Robert Larner, M.D. College of Medicine at the University of Vermont. “We are proud of the role UVM has played in advancing science that will save lives worldwide.”
Kirkpatrick served as principal investigator for the umbrella research funding award that supported early-stage clinical trials and immunology research on the vaccine at UVM. Kirkpatrick and colleagues began studying the candidate tetravalent (four-serotype) dengue vaccine in 2009 in collaboration with leaders in the dengue field: JHSPH professor Anna Durbin, M.D., and NIH virologist Steven Whitehead, Ph.D. Whitehead and colleagues at the NIH designed the candidate vaccine. Since 2009, more than 27 clinical trials have been conducted at UVM and JHSPH to develop this vaccine, yielding many major scientific and immunologic insights.
At UVM, the new dengue antiviral treatment investigation was led by Kristen Pierce, MD, co-director of the Vaccine Testing Center and professor of medicine, and by Durbin’s team at JHSPH. About 80 volunteers participated in clinical trials at the two sites.
The volunteers were randomly assigned to receive either the treatment or a placebo prior to receiving a dose of a mild strain of dengue virus. The study data published in NEJM showed that the treatment, an oral pan-dengue small molecular antiviral called Mosnodenivir, inhibits replication of dengue virus and prevents infection. An oral antiviral drug would be extremely useful during outbreaks and could be utilized by travelers and persons who are not able to receive a vaccine.
Allen Institute scientists are learning why vaccines can trigger a weaker response in older adults, around age 65, and what can be done to improve them. These insights open the door to designing more effective vaccines.
In the largest study of its kind, published in Nature, scientists discovered that T cells undergo profound and specific changes as we age. These changes, far from being random or a byproduct of chronic disease and inflammation, are a fundamental feature of healthy aging and will happen to all of us as we get older.
“We were surprised that inflammation is not driving healthy aging. We think inflammation is driven by something independent from just the age of a person,” said Claire Gustafson, PhD, assistant investigator at the Allen Institute and one of the lead authors of the study. “This is important because there’s been research showing similar findings that inflammation and aging don’t go hand in hand, and your immune system is just changing with age.”
The changes also point to why vaccines, including the annual flu shot and COVID-19 boosters, tend to be less effective in older adults.
The changes scientists discovered
T cells are a critical part of our immune system that help “train” B cells, to produce antibodies in response to viruses and vaccines. But this study found that memory T cells in older adults undergo a dramatic shift toward what is known as a “Th2-like” state, which is a change in gene expression that fundamentally alters how these cells respond to threats. Researchers found this shift directly affects B cells’ ability to generate strong antibody responses. In other words, the flu shot might still deliver the right viral components, but if the memory T cells aren’t functioning properly, the body struggles to respond effectively.
How this could lead to better vaccines
With this insight, doctors may be able to use a person’s immune profile to predict how well they’ll respond to a vaccine. Now that scientists can pinpoint how T cells become less effective with age, they can also start designing new vaccine formulas or immune-boosting treatments to address these issues.
Since T cells in older adults function differently, scientists could reformulate vaccines to compensate specifically for age-related cellular changes rather than using a one-size-fits-all approach. Gene-editing tools like CRISPR could also be used to reprogram a person’s T cells before vaccination, essentially re-programming older immune cells to make them respond to vaccines like younger cells do—like CAR-T cell therapy that reprograms immune cells to fight cancer.
Researchers say this work goes beyond just vaccines and reveals how our immune systems change in all of us as we get older and how our bodies fight age-related disease and viruses. It also opens the door to interventions like new therapies to restore key immune cells.
How researchers made the discovery
Scientists tracked more than 96 healthy adults ages 25–65 for over two years in collaboration with Benaroya Research Institute. The researchers then used cutting-edge techniques like single-cell RNA sequencing, proteomics, and spectral flow cytometry to profile the immune system of these individuals over time. The scientists then used this data on the immune system to create a detailed Human Immune Health Atlas, an online resource mapping 71 different immune cell types and how they change over time, and why those changes matter. Then, they applied this Atlas to study over 16 million individual immune cells from healthy adults 25–90+ years of age, offering an unprecedented tool for researchers worldwide to better understand, and support, the aging immune system. This online resource is the largest of its kind and freely available to researchers worldwide.
“This research illustrates how working collaboratively can make a significant impact on our understanding of the immune system, both now and in the future,” said Jane Buckner, MD, president of the Benaroya Research Institute. “It was made possible through the combined efforts of several Seattle-based research institutions, dedicated scientists, clinicians and research coordinators, as well as the individuals who generously volunteered their time, samples, and health information.”
The significance of this work extends beyond aging research and provides a roadmap for understanding how immune dysfunction develops over time, offering concrete targets for intervention and potentially transforming how we approach immune health across the entire human lifespan.
“There’s so much more information to be gained by looking at this dataset we’ve produced,” said Gustafson. “My hope is that it will be used for a long time to enable other researchers to look more deeply and find more insights into human immunity.”
A new mRNA vaccine stopped allergens from causing dangerous immune reactions and life-threatening inflammation in mice, according to researchers from the Perelman School of Medicine at the University of Pennsylvania and Cincinnati Children’s. The vaccine, outlined in the Journal of Clinical Investigation, may one day be tested and tailored to a variety of seasonal and food allergies.
“This is a potential breakthrough for millions of people worldwide who suffer from life-threatening allergies,” said Nobel laureate Drew Weissman, MD, PhD, Professor in Vaccine Research at Penn and co-lead of the study with Cincinnati Children’s Marc E. Rothenberg, MD, PhD.
Weissman, Penn colleagues Jilian Melamed, PhD, an assistant professor of Infectious Diseases, Mohamad-Gabriel Alameh, PhD, an assistant professor of Pathology and Laboratory Medicine, and the Cincinnati Children’s researchers led by Marc E. Rothenberg, MD, PhD, director of the division of Allergy and Immunology, modelled this new vaccine on the design of the COVID-19 mRNA lipid nanoparticle (LNP) vaccines.
This time, however, scientists tweaked the mRNA to instruct cells to produce proteins that resemble certain allergens. By presenting these proteins in a controlled way, the vaccine didn’t cause allergic reactions but did instruct the immune system to respond more appropriately in the future. And, when mice were later exposed to the respective allergens, the vaccines worked.
When mice with specific allergies were exposed to the allergens, none of the mice vaccinated with the respective allergy vaccine had an allergic reaction. Vaccinated mice had fewer allergy-related white blood cells, made fewer inflammation-causing proteins, and their lungs produced less mucus. Their airways were also protected against narrowing, which often happens during asthma, and they made special antibodies that protected against allergic reactions.
A platform with broad potential
Unlike traditional allergy shots, which involve repeated administration of purified allergens over months or years, the mRNA-based approach offers a more flexible solution. Because the mRNA can be tailored to encode proteins from different allergens, the platform could be adapted to treat a wide range of allergic conditions—from seasonal pollen allergies to food sensitivities and asthma. Additionally, many severe food allergies do not have vaccines to protect against severe allergic reactions.
“People with food allergies that can cause anaphylactic shock are rightfully fearful in social situations, eating out in public, sharing food, and engaging in other fun activities where there are food and allergens around,” said Weissman. “Allowing people to partake in foods they were never able to eat would be incredibly rewarding, but I’ll even be happy if we can one day introduce a vaccine that allows parents to breathe just a little easier when sending their kids to class birthday parties.”
The study represents a proof-of-concept that mRNA vaccines can be used not only to prevent infectious diseases but also to adjust immune responses in chronic conditions like allergies and even celiac disease. Researchers say the next steps include testing the vaccine’s safety in humans, determining how many allergens can be included in a single dose, and evaluating how long protection lasts.
“We saw mRNA vaccines save lives during the pandemic, and as the most-tested type of vaccine in history, we know it’s the safest and most effective vaccine ever created,” said Weissman. “We are deeply committed to continuing to uncover the potential of this technology.”
