Amid a global surge in measles cases, new research suggests that undernutrition may be exacerbating outbreaks in areas suffering from food insecurity. A study involving over 600 fully vaccinated children in South Africa found those who were undernourished had substantially lower levels of antibodies against measles.
Researchers from McGill University, UC Berkeley School of Public Health and the University of Pretoria tracked the children’s growth over time as an indicator of undernutrition and measured their antibody levels through blood tests. Children who were stunted around age three had an average of 24-per-cent-lower measles antibody levels by age five compared to their typical-sized peers.
The findings, published in Vaccine, suggest that undernutrition may affect the duration of vaccine protection.
This indicates that addressing child hunger could be a key piece of the puzzle in preventing viral outbreaks, said senior author Jonathan Chevrier, an Associate Professor at McGill.
A growing threat worldwide
Measles is a highly contagious viral infection that causes symptoms such as a rash, fever and cough, and can lead to severe complications, especially in young children. The disease is a threat in regions where it was once under control, including Canada, which in 2024 reported its highest number of cases in nearly a decade.
“Global measles cases declined from 2000 to 2016, but the trend reversed in 2018, driven in part by under-vaccination and the impact of the pandemic. Measles is now making a strong comeback in many parts of the world despite being preventable with vaccination and adequate immunity,” said co-author Brian Ward, Professor at McGill’s.
“We need to vaccinate children against infectious diseases that are preventable and ensure they are protected,” said first author Brenda Eskenazi, Professor at the University of California, Berkeley. “This is especially important now, given that many known diseases are expected to spread with climate change.”
About 22% of children under age five worldwide – approximately 148 million – were stunted in 2022, Chevrier added, with the highest rates in Asia and sub-Saharan Africa.
The team plans to monitor the children in the study as they grow older to understand whether the effects of early-life undernutrition persist.
Cervical cancer deaths have plunged dramatically among women under age 25, and researchers at MUSC Hollings Cancer Center believe this is likely due to HPV vaccination. Their study, published in JAMA, is the first to suggest the impact of HPV vaccination on cervical cancer deaths.
“We observed a substantial reduction in mortality – a 62% drop in cervical cancer deaths over the last decade, likely due to HPV vaccination,” said senior author Ashish Deshmukh, PhD, co-leader of the Cancer Prevention and Control Research Program. “We cannot think of any other reason that would have contributed to such a marked decline.”
The human papillomavirus, or HPV, causes nearly all cases of cervical cancer. The HPV vaccine was introduced in 2006. At first, it was available only to adolescents, but eligibility has since been expanded to include adults up to age 45 in some cases. In South Africa, an HPV vaccination programme started in 2014 for girls in public schools.
Previous studies have looked at the rates of HPV infection, precancer and cervical cancer incidence since the introduction of the vaccine, and all of those indicators have declined. The next logical step was to look at death rates, Deshmukh said.
Although cervical cancer is rare in women under age 25, it does occur. By examining deaths in this age group, researchers were able to see the early impact of the vaccine. Women who were 25 in 2021, the final year included in this study, would have been 10 years old when the vaccine was introduced.
The researchers looked at cervical cancer deaths in three-year blocks of time. Through the 1990s, there were between 50 and 60 cervical cancer deaths nationally in women under the age of 25 in each three-year block of time. During the 2019–2021 time period, there were only 13 deaths.
However, the team sounded an alarm. Healthy People 2030 has a goal of reaching an 80% HPV vaccination rate, but the Centers for Disease Control and Prevention reported earlier this year that only about 60% of 13 to 15 year olds have received the recommended doses.
“There has been a decline in HPV vaccination post COVID-19 in the most recent generation of U.S. adolescents. This is troubling as a decline in vaccination uptake would potentially lead to smaller gains,” Deshmukh said.
The groundbreaking mRNA Technology Transfer Programme, launched in 2021, has achieved what was once unthinkable: from zero mRNA manufacturing capabilities in low- and middle-income countries (LMICs) in 2020, the initiative is positioned towards establishing 11 state-of-the-art good manufacturing practices (GMP) certified mRNA manufacturing facilities across 10 countries by 2030 and a further five facilities following later.
With all manufacturers in the Programme working on R&D across various diseases, this network is designed to meet the Global South’s R&D and mRNA vaccine needs. It stands ready to respond to any future pandemic to secure mRNA vaccine access across continents.
The transformative Programme, established by the World Health Organization (WHO) and the Medicines Patent Pool (MPP), works with the South African Consortium, Afrigen, Biovac, the South African Medical Research Council (SAMRC), and the Department of Science and Innovation and programme partners in Kenya, Brazil, Indonesia, India, Egypt, Nigeria, Ukraine, Bangladesh, Senegal, Tunisia, Serbia, Pakistan, Vietnam, and Argentina.
The Programme, support by South Africa, France, Belgium, Canada, the European Union, Germany, Norway, and the ELMA Foundation, has propelled LMICs to the forefront of pandemic preparedness. It represents an unprecedented global effort to ensure equitable health solutions, enabling LMICs to respond rapidly and independently to global health crises.
Charles Gore, Executive Director of the Medicines Patent Pool, stated, “From a standing start in 2020, the Programme’s growth has been nothing short of remarkable. After successfully developing a COVID-19 vaccine as proof of concept, the Programme is now expanding to address many other diseases relevant to LMICs. We are now poised to establish a sustainable mRNA vaccine production capacity that will benefit millions across the Global South, truly redefining what health equity can look like on a global scale.”
In a significant step forward, Sinergium Biotech is researching a human avian influenza (H5N1) mRNA vaccine candidate, and four R&D consortia have been formed in Southeast Asia, with more expected across other regions. The vaccines developed through this initiative will be shared across participating LMICs.
Unprecedented Capacity for Pandemic Preparedness and Resilience
With the manufacturing companies across four continents all based in LMICs, the Programme has fundamentally altered the mRNA vaccine production landscape. The initiative is projected to yield at least 60 million doses annually by 2030, with the potential to scale up to larger volumes that could supply up to two billion doses in the event of a declared pandemic. Leveraging future dose-reduction technologies, the Programme would have the capacity to cover all the mRNA vaccine requirements of the Global South.
As of December 2024, the mRNA Technology Transfer Programme has made significant progress, with nearly all site assessments completed. Half of the participating manufacturers have finalised their technology plans, with the remaining plans scheduled for completion by December 2025. Over a quarter of these manufacturers will have successfully received the technology platform transfer from Afrigen by the end of 2024, with the rest to be completed in 2025, marking an important milestone in the Programme. By December 2026, all manufacturing partners are expected to have demonstrated the technology at their respective sites, culminating in the full transfer of mRNA technology across all participants.
Prof. Petro Terblanche, CEO of Afrigen, highlighted, “The mRNA Programme has not only achieved our initial goals but exceeded them in every way. Afrigen’s work with our global partners has shown that LMICs can lead in R&D and manufacturing, transforming healthcare outcomes from diseases that affect the Global South. This Programme yet again demonstrates the power of partnerships and global collaborations.”
Dr Martin Friede, Coordinator at WHO, emphasised, “This mRNA Technology Transfer Programme exemplifies the power of collaboration in global health. We are delighted that WHO and the partners have signed an MOU with Prof Drew Weissman of the University of Pennsylvania to promote R&D of mRNA products for public health. We hope other institutions will also follow and share knowhow. We are committed to securing the necessary support to see these efforts through so that LMICs have the scientific and material resources to maintain this unprecedented level of pandemic preparedness.”
The Critical Role of Funding
Despite remarkable progress, additional funding is required to fully achieve the Programme’s ambition. An estimated US$200 million is needed to advance all manufacturers to GMP standards and continue to strengthen the R&D pipeline in support of at least 12 mRNA products currently in development. Encouragingly, Programme success has already attracted substantial catalytic co-investments. For example, for every dollar contributed by the Programme in the AFRO region, an estimated US$17 has been invested by regional stakeholders and other public health organisations.
Maternal antibodies passed across the placenta can interfere with the response to the malaria vaccine, which would explain its lower efficacy in infants under five months of age, according to research led by the Barcelona Institute for Global Health (ISGlobal), in collaboration with seven African centers (CISM-Mozambique, IHI-Tanzania, CRUN-Burkina Faso, KHRC-Ghana, NNIMR-Ghana, CERMEL-Gabon, KEMRI-Kenya).
The findings, published in Lancet Infectious Diseases, suggest that children younger than currently recommended by the WHO may benefit from the RTS,S and R21 malaria vaccines if they live in areas with low malaria transmission, where mothers have less antibodies to the parasite.
The world has reached an incredible milestone: the deployment of the first two malaria vaccines –RTS,S/AS01E and the more recent R21/Matrix-M– to protect African children against malaria caused by Plasmodium falciparum. Both vaccines target a portion of the parasite protein called circumsporozoite (CSP) and are recommended for children aged 5 months or more at the moment of the first dose.
“We know that the RTS,S/AS01E malaria vaccine is less effective in infants under five months of age, but the reason for this difference is still debated,” says Carlota Dobaño, who leads the Malaria Immunology group at ISGlobal, a centre supported by “la Caixa” Foundation.
To investigate this, Dobaño and her team analysed blood samples from more than 600 children (age 5-17 months) and infants (age 6-12 weeks) who participated in the phase 3 clinical trial of RTS,S/AS01E. Using protein microarrays, they measured antibodies against 1000 P. falciparum antigens before vaccination to determine if and how malaria exposure and age affected IgG antibody responses to the malaria vaccine.
“This microarray approach allowed us to accurately measure malaria exposure at the individual level, including maternal exposure for infants and past infections for older children,” says Didac Maciá, ISGlobal researcher and first author of the study.
The role of maternal antibodies
The analysis of antibodies to P. falciparum in children who had received a control vaccine instead of RTS,S/AS01E revealed a typical “exposure” signature, with high levels in the first three months of life due to the passive transfer of maternal antibodies through the placenta, a decline during the first year of life, and then a gradual increase as a result of naturally acquired infections.
In children vaccinated with RTS,S/AS01E, antibodies induced by natural infections did not affect the vaccine response. However, in infants, high levels of antibodies to P. falciparum, presumably passed from their mothers during pregnancy, correlated with reduced vaccine responses. This effect was particularly strong for maternal anti-CSP antibodies targeting the central region of the protein. Conversely, infants with very low or undetectable maternal anti-CSP IgGs exhibited similar vaccine responses as those observed in children.
The molecular mechanisms underlying this interference by maternal antibodies are not fully understood, but the same phenomenon has been observed with other vaccines such as measles.
Overall, these findings confirm something that was already suspected but not clearly demonstrated: despite their protective function, maternal anti-CSP antibodies, which decline within the first three to six months of life, may interfere with vaccine effectiveness. The higher the level of malaria transmission, the more maternal antibodies are transmitted to the baby, resulting in lower vaccine effectiveness. These findings further suggest that infants below five months of age may benefit from RTS,S or R21 vaccination in low malaria transmission settings, during outbreaks in malaria-free regions, or in populations migrating from low to high transmission settings.
“Our study highlights the need to consider timing and maternal malaria antibody levels to improve vaccine efficacy for the youngest and most vulnerable infants,” says Gemma Moncunill, ISGlobal researcher and co-senior author of the study, together with Dobaño.
New research published in Nature has shown that the recombinant shingles vaccine, as with the live version, might have a protective effect against dementia.
While evidence is emerging that the live herpes zoster (shingles) vaccine might protect against dementia, it has now been replaced by recombinant vaccines in many countries. But a lack of data meant that whether the recombinant vaccines conferred the same benefit was unknown. Fortunately, since there was a rapid switch from live to recombinant vaccines, there was an opportunity for a natural experiment to compare the risk of dementia between vaccine types.
The study demonstrated that the recombinant vaccine is associated with a significantly lower risk of dementia in the 6 years post-vaccination. Specifically, receiving the recombinant vaccine is associated with a 17% increase in diagnosis-free time, translating into 164 additional days lived without a diagnosis of dementia in those subsequently affected.
The recombinant shingles vaccine was also associated with lower risks of dementia than were two other vaccines commonly used in older people: influenza and tetanus–diphtheria–pertussis vaccines. The effect was robust across multiple secondary analyses, and was present in both men and women but was greater in women. These findings should stimulate studies investigating the mechanisms underpinning the protection and could facilitate the design of a large-scale randomised control trial to confirm the possible additional benefit of the recombinant shingles vaccine.
Hepatitis C virus. Credit: Scientific Animations CC4.0
Around 58 million people suffer from chronic inflammation caused by the hepatitis C virus, and 300 000 people die from the disease every year. So far, no treatment has successfully managed to reduce the global prevalence of hepatitis C, prompting scientists to start looking for a vaccine. But limited knowledge of the protein complex that enables the virus to infect the cells has made this difficult.
A new study by a cross-disciplinary research team at the University of Copenhagen is about to change that. It is out now in the journal Nature.
“We are the first ever to identify the protein complex at the surface of the hepatitis C virus that enables it to bind to our cells,” says Associate Professor Jannick Prentø.
“This knowledge of the structure of the protein complex will enable us to design vaccine candidates that can prevent the virus from infecting the cells,” says Postdoc Elias Augestad.
The protein complex helps the virus bind to the cells. In the corona virus, it is a so-called spike protein with the well-known spikes. In the hepatitis C virus, the structure is different, but the function of the protein complex is the same.
Paves the way for vaccine development
The study can be considered a blueprint for HCV vaccine development. Scientists hope to be able to use the new knowledge to develop a vaccine which will make the immune system produce antibodies that bind effectively to the surface of the hepatitis C virus and thus render it harmless.
“Expressing and cleaning up the protein complex is extremely difficult, which is why it has not been done before. The structure of these proteins on the surface of the hepatitis C virus makes them extremely vulnerable. Researchers did not know what they were dealing with, and therefore, whenever someone tried to reproduce these protein structures in the lab they would fall apart before they could get a chance to study them,” says Associate Professor Jannick Prentø.
“But we managed to describe their structure, and this has enabled us to reproduce these protein complexes outside the cell and study them closely,” says Associate Professor Pontus Gourdon.
A marker used to measure immunisation coverage is to look at whether children received three doses of the vaccine against diphtheria, tetanus and pertussis. Photo by Mufid Majnun on Unsplash
By Elri Voigt
New data from the World Health Organization (WHO) and UNICEF show that globally childhood immunisation coverage stalled in 2023, while in South Africa it decreased. Elri Voigt unpacks the new data and asks local experts to put it in context.
A new report found that vaccination coverage rates around the world have not yet returned to levels seen in 2019, before the COVID-19 pandemic disrupted immunisation programmes.
There has been no meaningful change in immunisation coverage between 2022 and 2023, according to the WHO and UNICEF report published in July. It means progress in immunisation coverage has effectively stalled, leaving 2.7 million additional children who are either unvaccinated or under-vaccinated compared to pre-pandemic levels in 2019.
A marker used to measure immunisation coverage is to look at whether children received three doses of the vaccine against diphtheria, tetanus and pertussis – referred to as DTP3. Global coverage for DTP3 stalled at 84% in 2023, according to the report.
At the same time, the number of children worldwide who have not received any vaccinations has increased. We refer to these kids as zero-dose children. Ten countries account for 59% of all zero-dose children, with the global number in 2023 rising to 14.5 million compared to 13.9 million in 2022, according to the report.
Coverage slightly down in SA
Data from the report showed a slight decrease for a number of outcome measures in South Africa between 2022 and 2023. It was one of 14 countries in the African region that saw a decrease in coverage for DTP1 (the first dose of the vaccine for diphtheria, tetanus and pertussis), slipping from 87% in 2022 to 81% in 2023. Coverage for DTP3 also decreased, falling from 85% in 2022 to 79% in 2023.
South Africa was also one of 10 countries in the African region that saw a decrease in coverage for the first dose of the measles vaccine, and was singled out by the report as having the sharpest decline in coverage in the region between 2022 and 2023. Measles coverage dropped from 86% in 2022 to 80% in 2023.
Commenting on the accuracy of the new data, Professor Shabir Madhi, Dean at the Faculty of Health Sciences at the University of Witwatersrand (Wits), said it used administrative data, which can bias the estimates. He explained that the report bases vaccine coverage on the number of vaccines procured by government and deployed to facilities. For example, if a facility gets 100 doses of the measles vaccine and ends up discarding 50 doses, that doesn’t necessarily get reported.
The WHO acknowledges the potential for data inaccuracies. It stated that they calculate the estimated percentage of immunisation coverage by dividing the number of doses administered to a target population by the estimated number of people in that target population.
Madhi said a more accurate picture of childhood immunisation coverage in the country can be found in National Vaccine coverage surveys, like the Expanded Programme on Immunisation (EPI) National Coverage survey. Spotlight previously reported on results from the most recent EPI survey conducted in 2019.
Madhi said it appears the new report did not incorporate data from the EPI survey. However, even without this data, he said the WHO estimates are not too far off the local data. He remarked that he doesn’t feel “too strongly either way” about the accuracy of the WHO data since the bottom line is vaccine coverage in the country is lagging.
“Fluctuations in immunisation coverage are not uncommon,” Dr Haroon Saloojee, a professor of Child Health at Wits University told Spotlight. “One should not make too much of a fall or increase in coverage rates over one year, unless it is drastic.”
Data from the WHO report for vaccine coverage in South Africa between 2018 and 2022 had actually showed an overall upward trend, which was “promising”, according to Saloojee. However, he said the latest data from the report “holds no good news for South Africa” because the dip in coverage in 2023 was noteworthy.
How does SA compare?
“South Africa’s performance is moderate when compared globally, and poor compared to other high-middle income countries,” said Saloojee. “Considering that South Africa is a high-middle-income country, we should be performing much better in all our health indicators.”
He pointed out that countries in a similar bracket like Cuba and Uruguay have achieved high immunisation coverage through robust healthcare systems and effective public health policies.
Regarding zero-dose children, the report ranked South Africa 6th worst in the African region. In 2022, the country ranked 13th. With a total of 220 000 zero-dose children, the country accounted for 3% of all zero-dose children in the African region. Nigeria had the highest percentage at 32% of all zero-dosed children in the region, followed by Ethiopia with 14%.
‘Dysfunctionality of primary healthcare’
Apart from the international comparisons, Madhi pointed out that South Africa is not meeting its own targets of having at least 90% of children in each district fully vaccinated.
The EPI survey found that only seven of the 52 districts in the country were able to achieve the national target of 90% of children fully vaccinated under one year of age. Together, the data from the survey and the WHO clearly shows that childhood immunisation targets are not being met in the country.
For Madhi, the results from the EPI survey “speaks to dysfunctionality of primary health care in the country”. He said the immunisation of children, which is the bedrock of primary healthcare when it comes to children, acts as a “canary in the mine with regards to how well primary healthcare is working”.
He said South Africa is a leader in the field when it comes to evaluating and introducing vaccines to the public immunisation programme. But when it comes to implementation, for the vast majority of districts we “are falling completely flat on our face and coming short in terms of reaching our own targets”.
Implications for children
The health implications for children who are not unvaccinated or only partially vaccinated are significant.
“They are less protected against what can be life threatening diseases. And those life-threatening diseases include diseases such as measles, but also other life-threatening diseases such as pneumonia,” Madhi said.
“We’re selling ourselves short as a country in addition to actually compromising the health of children by not ensuring that we’re doing everything that’s possible to actually get children to be vaccinated,” Madhi added. “It also comes with other consequences, so it sort of lends South Africa to be more prone to outbreaks.”
Saloojee added that it is also likely that children who are not fully vaccinated are “not receiving many of the other health, education and social development services all children require and that is being provided by government, such as early childhood development services and child support grants”.
The reasons for immunisation coverage lagging are complex and the responsibility for fixing the problem lies with more than just one entity. Spotlight previously reported on some of the reasons children are remaining unvaccinated or under-immunised as identified by the EPI survey.
Madhi said there needs to be a fundamental relook at the country’s immunisation programme. Proper governance structures need to be put in place and the programme will need to be implemented all the way down to the sub-districts. There is also a need for real-time data and monitoring of that data so interventions can be done when children are missing their immunisations. He also suggested ring-fencing funds for vaccines, at either a national or provincial level, to ensure that money earmarked for vaccines are used for that purpose so as to ensure less stock-outs.
“The immunisation programme hasn’t changed much from what I can gather over the past 20 years, let alone the past 10 years. So we can’t expect a different outcome if the strategy that we’re using which has failed is the strategy that you continue pursuing,” Madhi said.
Saloojee said the National Department of Health can play a pivotal role in strengthening the immunisation programme by “providing leadership, resources, and policy support”. He said that to his knowledge the health department is currently preparing a national immunisation strategy to take us to 2030, but the draft is not up to scratch. The strategy, he says, will need to offer clear objectives, establish realistic indicators of, and targets for, measuring success, and attract a fully funded mandate.
Spotlight asked the National Department of Health for comment on the new WHO report and how it plans to respond to improve immunisation coverage. While the department acknowledged our questions, they did not provide comment by the time this article was first published.
Professor Shabir Madhi of Wits University. Photo: supplied.
By Biénne Huisman
Amid the uncertainty of the early days of the COVID-19 pandemic, Professor Shabir Madhi often stood out for his clarity of thought in making sense of rapidly evolving scientific evidence. Biénne Huisman chatted to Madhi about vaccines, ongoing challenges with the Gauteng health department, and being outspoken about issues such as the war in Gaza.
Professor Shabir Madhi became known to many in South Africa for leading the charge in two of the first COVID-19 vaccine clinical trials conducted in Africa – those for the AstraZeneca and Novavax vaccines. At a time of much scientific uncertainty, he was often quoted in the press – gaining a reputation for keeping his cool and calling things as he saw them based on available evidence.
He spoke out against the politicisation of science and was a staunch advocate for access to vaccines, especially for older people at higher risk of severe illness and death. He wasn’t afraid to ruffle feathers, openly criticising government’s COVID-19 vaccine communication efforts and arguing that government should take vaccines to the people, rather than the other way around. He called for the ending of strict lockdowns, before many others did so. Reflecting on his reputation for not holding back on his beliefs, he admits to “having a short fuse, especially when people are talking nonsense – or what I consider to be entirely off the mark”.
What may be less obvious to the public, is that Madhi’s healthcare impact precedes COVID by decades.
Internationally respected for his research into paediatric infectious diseases, his work has helped to save the lives of hundreds of thousands of children and informed World Health Organization policy (WHO) – notably relating to the pneumococcal conjugate vaccine (to prevent pneumonia and meningitis) and the rotavirus vaccine (to prevent diarrhoeal disease in young children).
His work continues. Just last year a landmark study, led in South Africa by Madhi’s Vaccines and Infectious Diseases Analytics Research Unit at the University of the Witwatersrand (Wits), found that immunisation of pregnant women safely protected their unborn babies from respiratory syncytial virus (RSV). As Spotlight reported at the time, researchers estimate the vaccine can save thousands of young lives.
Speaking to Spotlight over Zoom from Wits in Johannesburg, where he is Dean of Health Sciences, Madhi relays his love of treating kids – who “most importantly, don’t lie, and who are the most vulnerable”.
“Accidental vaccinologist”
Madhi has been described as an “accidental vaccinologist”. Shrugging inside a navy suit, he says he never intended to become a physician, let alone a professor in vaccinology. At medical school at Wits, he nearly dropped out after a month.
As a child, growing up in Lenasia, Madhi wanted to become an engineer. But born to a mathematics teacher father and a stay at home mum, money was tight. His only opportunity to attend university presented itself via a bursary in medicine.
“I only really started to enjoy medicine once I specialised in paediatrics,” he says. “But more importantly, that’s when I realised the huge potential that existed in medicine to make a difference, particularly the potential for vaccines to make a big difference over a short period of time – not on an individual level, but at a community level. And that’s what really drove me into the space of research.”
While doing his peadiatric training at Chris Hani Baragwanath Academic Hospital (he obtained a master’s degree in paediatrics from Wits in 1998), it struck him that the leading causes of death among children were entirely preventable.
“Back then, close to 750 000 children were dying of measles globally; half of those deaths were happening in Africa, despite the vaccine for measles being available since the 1970s. South Africa was one of the countries with a poor public immunisation programme; up until 1992 South Africa didn’t have a public immunisation programme.”
In 2009, in a first on the African continent, pneumococcal and rotavirus vaccines were finally officially rolled out in South Africa.
“While I was training at Baragwanath, there was a ward just for children with gastroenteritis or diarrhoea,” he recalls. “But six months after we introduced the rotavirus vaccine in South Africa [in 2009], we shut down the diarrhoea ward at Baragwanath and probably every other diarrhoea ward in the country.”
Contributing internationally
Today Madhi’s CV is long. He sits on scores of scientific advisory committees, attending conferences and delivering talks around the world.
Since 2019, he has served on a global panel of experts convened by the WHO, the Strategic Advisory Group of Experts on Immunization (SAGE), of which he now is deputy chair. He also chairs the SAGE working group on polio.
“I’m really enjoying SAGE at the moment,” he says. “This is where I think I am making a meaningful contribution. It really is an eye opener to the different types of research that’s taking place globally; but also the type of challenges we face in terms of ensuring that children are adequately immunised.
“It’s great to be working on new vaccines, coming up with new vaccines; but that’s a meaningless exercise unless you can ensure that those vaccines are getting into the arms of children – because that is what saves lives. So yes, dealing with issues around implementation and advocacy.”
SAGE requires frequent trips to Geneva, where the WHO is based.
Our discussion turns to business travel – the amount required for a researcher to remain “relevant and competitive”. With typical candour, Madhi outlines challenges faced by researchers from the global south.
“I think coming from South Africa, coming from the African continent, it’s more of a challenge for researchers to establish themselves, for a number of reasons. Firstly to become known in the international space, you probably need to deliver so much more than what is expected from our northern hemisphere counterparts.
“Then in addition to the inconvenience of needing to travel so often, there are subtle things which people in the northern hemisphere don’t have to deal with. Needing to get visas and dealing with customs officials when entering countries.
“It can become an extremely unpleasant experience, and you really need to swallow your pride given what is blatant racism at times. For example, nowadays I refuse to fly through Germany because the customs office in Frankfurt is probably the worst I have encountered. All of a sudden, they would keep me and question me for both arrival, as well as departure…”
Local challenges
The discussion turns back to South Africa, and health challenges in his home province of Gauteng. Here also Madhi has tried to make a difference, but it hasn’t been plain sailing.
Commenting on a floundered memorandum of agreement (MOA) signed between Wits and the Gauteng Department of Health in June 2022, Madhi says: “The bottom line unfortunately; the Gauteng Department of Health simply doesn’t have stability of leadership. At the level of the MEC in particular; I mean since I’ve been dean, there’s been about four or five heads of department. And it becomes difficult to follow through with any of these programmes.”
Madhi adds that Wits university executives had worked on the memorandum for seven years. The agreement set out a plan to combine university and government resources in “academic health complexes” for enhanced service delivery. But the Department of Health put it on hold three months later, following a related Public Service Commission inquiry.
He explains: “They convened this big workshop, spending probably a mini fortune, to basically facilitate the establishment of an MOA, not just between Wits and the Department of Health, but between the Department of Health and many other academic hospitals in the province. Because of the intervention, the Department of Health indicated that they weren’t going to implement our MOA until that particular commission concluded their work. But since then, there’s been absolutely no report from that meeting.”
Not afraid to speak out
On social media, Madhi speaks out about atrocities being committed in Gaza.
To Spotlight, he says leadership holds no place for neutrality.
“As part of leadership, and I do consider myself a leader in the different roles that I play – either in my research unit or currently as university dean – you need to be prepared to take a stance. You can’t remain neutral on positions. You need to interrogate facts. And once having interrogated the facts, you need to reach a conclusion; then follow through with what is required, if there’s anything that needs to be implemented.”
Madhi says his leadership style was honed during childhood. “Not being afraid to speak out, it does get me into trouble quite often,” he says, laughing. “I think that’s just part of my upbringing, being an activist during apartheid in the Lenasia Youth League and other activist organisations. My upbringing was, when things are not what it’s meant to be, you speak out; you champion the right cause.”
These days Madhi lives in Northcliff with his wife, with whom he has two children. His favourite football team is Arsenal and a book he says he recently enjoyed was The Covenant of Water – a three generation family account set in India, by physician and author Abraham Verghese.
The new vaccine, tested in primates against the 1918 flu virus, would be a “one and done” shot
Photo by Mika Baumeister on Unsplash
New research led by Oregon Health & Science University reveals a promising approach to developing a universal influenza vaccine – one that also confers lifetime immunity against an evolving virus. The study, published in Nature Communications, tested an OHSU-developed vaccine platform against the virus considered most likely to trigger the next pandemic.
Researchers reported the vaccine generated a robust immune response in nonhuman primates that were exposed to the avian H5N1 influenza virus. But the vaccine wasn’t based on the contemporary H5N1 virus; instead, the primates were inoculated against the influenza virus of 1918 that killed millions of people worldwide.
“It’s exciting because in most cases, this kind of basic science research advances the science very gradually; in 20 years, it might become something,” said senior author Jonah Sacha, PhD, professor and chief of the Division of Pathobiology at OHSU’s Oregon National Primate Research Center. “This could actually become a vaccine in five years or less.”
Researchers reported that six of 11 nonhuman primates inoculated against the 1918 flu virus survived exposure to one of the deadliest viruses in the world today, H5N1. In contrast, a control group of six unvaccinated primates exposed to the H5N1 virus succumbed to the disease.
Sacha said he believes the platform “absolutely” could be useful against other mutating viruses, including SARS-CoV-2.
“It’s a very viable approach,” he said. “For viruses of pandemic potential, it’s critical to have something like this. We set out to test influenza, but we don’t know what’s going to come next.”
A senior co-author from the University of Pittsburgh concurred.
“Should a deadly virus such as H5N1 infect a human and ignite a pandemic, we need to quickly validate and deploy a new vaccine,” said co-corresponding author Douglas Reed, Ph.D., associate professor of immunology at the University of Pittsburgh Center for Vaccine Research.
Finding a stationary target
This approach harnesses a vaccine platform previously developed by scientists at OHSU to fight HIV and tuberculosis, and in fact is already being used in a clinical trial against HIV.
The method involves inserting small pieces of target pathogens into the common herpes virus cytomegalovirus, or CMV, which infects most people in their lifetimes and typically produces mild or no symptoms. The virus acts as a vector specifically designed to induce an immune response from the body’s own T cells.
This approach differs from common vaccines – including the existing flu vaccines – which are designed to induce an antibody response that targets the most recent evolution of the virus, distinguished by the arrangement of proteins covering the exterior surface.
“The problem with influenza is that it’s not just one virus,” Sacha said. “Like the SARS-CoV-2 virus, it’s always evolving the next variant and we’re always left to chase where the virus was, not where it’s going to be.”
The spike proteins on the virus exterior surface evolve to elude antibodies. In the case of flu, vaccines are updated regularly using a best estimate of the next evolution of the virus. Sometimes it’s accurate, sometimes less so.
In contrast, a specific type of T cell in the lungs, known as effector memory T cell, targets the internal structural proteins of the virus, rather than its continually mutating outer envelope. This internal structure doesn’t change much over time – presenting a stationary target for T cells to search out and destroy any cells infected by an old or newly evolved influenza virus.
Success with a century-old template
To test their T cell theory, researchers designed a CMV-based vaccine using the 1918 influenza virus as a template. In a highly secure biosafety level 3 laboratory at the University of Pittsburgh, they exposed the vaccinated nonhuman primates to small particle aerosols containing the avian H5N1 influenza virus – an especially severe virus that is currently circulating among dairy cows in the US.
Remarkably, six of the 11 vaccinated primates survived the exposure, despite the century-long period of virus evolution.
“It worked because the interior protein of the virus was so well preserved,” Sacha said. “So much so, that even after almost 100 years of evolution, the virus can’t change those critically important parts of itself.”
The study raises the potential for developing a protective vaccine against H5N1 in people.
“Inhalation of aerosolised H5N1 influenza virus causes a cascade of events that can trigger respiratory failure,” said co-senior author Simon Barratt-Boyes, PhD, professor of infectious diseases, microbiology and immunology at Pitt. “The immunity induced by the vaccine was sufficient to limit virus infection and lung damage, protecting the monkeys from this very serious infection.”
By synthesising more up-to-date virus templates, the new study suggests CMV vaccines may be able to generate an effective, long-lasting immune response against a wide suite of new variants.
“I think it means within five to 10 years, a one-and-done shot for influenza is realistic,” Sacha said.
Xylazine, only intended for animals, is being added to opioids and cocaine, with deadly effects. Photo by Colin Davis on Unsplash
Xylazine is an FDA-approved sedative and pain reliever for use in animals, but it has severe adverse effects when used in humans. Now, it is now being added illicitly to opioids, like fentanyl and heroin, as well as cocaine – leading to a sharp rise in overdose deaths.
Scripps Research chemical biologists have developed a vaccine to block the effects of xylazine’s toxicity. The vaccine works by training the immune system to attack the drug, which is described in a new paper published in Chemical Communications.
“We demonstrated that a vaccine can reverse the symptoms of a xylazine overdose in rodents,” says study senior author Kim D. Janda, PhD, professor of chemistry at Scripps Research. “There is currently no remedy for xylazine poisoning other than supportive care, thus, we believe our research efforts and the data we have provided will pave the way for an effective treatment in humans.”
The rapid increase in lethal drug overdoses attributed to xylazine combined with fentanyl prompted the White House Office of National Drug Control Policy to declare this combination an emerging threat to the United States. Xylazine intoxication presents similarly to opioid overdose, causing respiratory and central nervous system depression, and it can heighten the effects of opioids. However, naloxone – typically administered to reverse the effects of opioids – does not tackle the impact of xylazine, highlighting the need for effective measures to treat acute toxicity caused by xylazine.
Researchers suspect xylazine works by reducing blood flow to the brain, among other areas of the body. The drug also causes non-healing skin lesions and wounds, often located on the forearms and lower legs, that can require amputation in some cases – giving it the nickname “zombie drug.”
Although no treatment currently exists, targeted vaccines may offer a solution. Antibodies from vaccination can target toxins as well as viruses and bacteria. But sometimes molecules are too small to initiate an immune response, as is the case with xylazine. So, to circumvent this problem, the researchers created a vaccine using a design principle that Janda pioneered, which relies on pairing the drug molecule (called a hapten) with a larger carrier molecule (a protein) and an adjuvant.
In this study, the scientists combined a xylazine hapten with multiple different protein types, to see which combination would create a robust immune response against xylazine. The team tested three vaccine formulations (termed TT, KLH and CRM197, based on the protein involved) to see which vaccine cocktail could help rodents after being challenged with xylazine. One of the three vaccines (TT) significantly increased movement in mice given xylazine after 10 minutes, while two of the three vaccines (TT and KLH) led to an improvement in breathing.
The scientists also examined how these vaccines would limit xylazine blood brain barrier, (BBB) permeation, a filtering mechanism that scrutinizes drug penetration. When xylazine was injected, it immediately crossed into the brain to bind with receptors. Antibodies typically cannot navigate the BBB; however, two of the three vaccines (TT and KLH) showed a strong ability to stop xylazine from reaching its receptors in the brain, limiting its detrimental effects.
A provisional patent has been filed on the research. In the future, his team will build off this work to create a bifunctional antibody that will reverse both fentanyl and xylazine’s toxicity simultaneously, something that naloxone cannot do.
“A monoclonal antibody treatment could be given in tandem with the vaccine to provide both immediate and long-term protection from both opioid substance use disorders as well as opioid-xylazine overdoses,” says Janda. “This strategy could make a significant impact on the opioid epidemic.”
