The World Health Organization warns that global health funding cuts are paving the way for a resurgence of diseases that had been brought to the brink by vaccination.
One example of prior success is Africa’s “meningitis belt”, spanning parts of sub-Saharan Africa, where vaccination campaigns had successfully eliminated meningitis A. Likewise, yellow fever and related deaths were drastically cut by improved routine immunisation and emergency vaccine stockpiles.
The WHO says that this hard-won progress is now threatened. “Funding cuts to global health have put these hard-won gains in jeopardy,” warned Tedros Adhanom Ghebreyesus, WHO Director-General.
Outbreaks on the rise
In 2023, measles cases were estimated at more than 10.3 million – a 20% year-on-year increase. In a statement marking the beginning of World Immunization Week,the WHO, UN Children’s Fund UNICEF and their partners warned that this upward trend is expected to continue into 2025.
After years of declining cases in Africa thanks to improved vaccine access, yellow fever is also making a return. The start of 2025 has already seen a rise in outbreaks across the continent, with cases also confirmed in the Americas.
The threat of vaccine misinformation
Vaccination efforts are increasingly under pressure due to a combination of misinformation, population growth, humanitarian crises, and funding cuts.
Earlier this month, a WHO review across 108 countries found that nearly half are experiencing moderate to severe disruptions to vaccination campaigns, routine immunisations, and supply chains due to falling donor support.
“The global funding crisis is severely limiting our ability to vaccinate over 15 million vulnerable children in fragile and conflict-affected countries against measles,” said Catherine Russell, Executive Director of UNICEF.
High healthcare returns on vaccination
Vaccines save around 4.2 million lives each year, protecting against 14 different diseases. Almost half of those lives are saved in Africa.
Despite this, falling investment now risks the re-emergence of diseases once thought to be under control.
Health experts emphasise that immunisation is one of the most cost-effective health interventions. Every $1 invested in vaccines brings an estimated return of $54 through better health and economic productivity.
UNICEF, WHO, and their partners are calling on parents, the public, and political leaders to support immunisation programmes and ensure long-term investment in vaccines and public health systems.
Squamous cancer cell being attacked by cytotoxic T cells. Image by National Cancer Institute on Unsplash
The concept of using vaccines to treat cancers has been around for several decades. A vaccine was first approved for prostate cancer in 2010, and another was approved in 2015 for melanoma. Since then, many therapeutic – as opposed to preventive – cancer vaccines have been in development, but none approved. One hurdle is the difficulty in finding antigens in tumours that look foreign enough to trigger an immune response.
Researchers at Tufts have now developed a cancer vaccine that makes tumour antigens more visible to the immune system, leading to a potent response and a lasting immunological memory that helps prevent tumour recurrence. Their vaccine avoids the need to hunt down a specific tumour antigen, instead relying on a digested mix of protein fragments called a lysate that can be generated from any solid tumour.
The vaccine they produced worked against multiple solid tumours in animal models, including melanoma, triple-negative breast cancer, Lewis lung carcinoma, and clinically inoperable ovarian cancer.
Developed by a team led by postdoctoral scholar Yu Zhao and Qiaobing Xu, professor of biomedical engineering, the method builds on earlier work expressing specific antigens for an enhanced immune response by making lipid nanoparticles that carry mRNA into the lymphatic system.
“We have significantly improved the cancer vaccine design by making it applicable to any solid tumour from which we can create a lysate, possibly even tumours of unknown origin, without having to select mRNA sequences, and then conjugating another component called AHPC that helps channel the protein fragments from the cancer cells into the immunological response pathway,” said Xu.
Unlike traditional vaccines designed to prevent infectious diseases caused by bacteria or viruses, cancer vaccines work by stimulating the body’s immune system to recognise and attack cancer cells. Unlike most vaccines against pathogens, they are designed to be therapeutic rather than preventive, acting to eliminate an existing disease. Some preventive cancer vaccines do exist, but they are generally targeted to viruses that are linked to cancers, such as HPV.
The key to the increased potency of the new cancer vaccine lies in its ability to direct tumour-derived antigens into a cellular pathway that efficiently presents the antigens to the immune system.
Rounding up the antigens and getting them into an antigen presenting cell like a macrophage or dendritic cell (the police stations, if we continue with the analogy) is generally an inefficient process for tumor antigens. This is where the Tufts research team applied a two-stage method to power up the process.
First, to make sure they round up all tumour proteins-of-interest, they modified the mix of tumour proteins with the AHPC molecule, which in turn recruits an enzyme to put a tag on the protein called a ubiquitin. It allows the cell to identify and process the protein into fragments for presentation to the immune system.
The researchers then packaged the AHPC-modified tumour proteins into tiny lipid nanoparticles, specifically designed to home in on lymph nodes, where most antigen-presenting cells can be found.
Tested in animal models of melanoma, triple-negative breast cancer, Lewis lung carcinoma, and inoperable ovarian cancer, the vaccine elicited a strong response by cytotoxic T cells, which attack the growing tumours, suppressing further growth and metastasis.
“Fighting cancer has always been an arsenal approach,” said Xu. “Adding cancer vaccines to surgical excision, chemotherapy, and other drugs used to enhance cytotoxic T cell activity could lead to improved patient responses and longer-term prevention of cancer recurrence.”
Whooping cough, or pertussis, was once a leading cause of death for children worldwide before the introduction of vaccines in the 1940s. In the decades since, the bacterial disease was nearly eradicated in the U.S., with fatalities falling to double digits each year.
But the disease has made a troubling comeback in recent years as vaccine coverage declined after the COVID-19 pandemic. In 2024, several outbreaks left public health officials and hospitals scrambling to accommodate a sudden influx of patients, primarily infants, who are often too young to be vaccinated and suffer the most severe symptoms.
Now, new research from The University of Texas at Austin could aid in improving whooping cough vaccines to once again push this disease toward eradication by targeting two key weaknesses in the infection.
A New Target
Against this backdrop, a team of researchers, including members of UT’s McKetta Department of Chemical Engineering and Department of Molecular Biosciences, has made significant strides in understanding and enhancing pertussis immunity. One of the things that makes pertussis infections dangerous is pertussis toxin (PT), a chemical weapon produced by the bacteria that weakens a patient’s immune response and causes many of the severe symptoms associated with whooping cough.
The new research, described in a new study published in the Proceedings of the National Academy of Sciences, focuses on two powerful antibodies, hu11E6 and hu1B7, which neutralise the PT in different ways.
Using cutting-edge cryo-electron microscopy approaches, the researchers identified the specific epitopes on PT where these antibodies bind. Epitopes are chemical targets the immune system can zero in on to fight pathogens. Hu11E6 blocks the toxin from attaching to human cells by interfering with sugar-binding sites, while hu1B7 prevents the toxin from entering cells and causing harm. These findings are the first to precisely map these critical regions, providing a blueprint to improve vaccines.
“There are currently several promising new pertussis vaccines in the research and clinical trial phases,” said Jennifer Maynard, professor of chemical engineering at the Cockrell School of Engineering and corresponding author of the new study. “Our findings could be incorporated into future versions quite easily, improving overall effectiveness and longevity of protection.”
She pointed to innovations like mRNA technology used in the COVID-19 vaccine, as well as breakthroughs in using genetic engineering on pertussis toxin (PTgen) to generate safer and more potent new recombinant acellular pertussis vaccines as technologies preserving neutralizing epitopes that can combine with her team’s new findings.
“Training the immune system to target the most vulnerable sites on the toxin is expected to create more effective vaccines,” Maynard said. “And the more effective and longer-lasting a vaccine is, hopefully, the more people will take it.”
In addition to helping guide future vaccine designs, the hu1B7 and hu11E6 antibodies themselves hold promise as therapeutic medicines for infected and high-risk infants. Previous work by Maynard and colleagues show that they can prevent the lethal aspects of pertussis infection. UT researchers are actively seeking partnerships to develop ways to prevent lung damage and death in newborns exposed to the disease.
A Persistent Threat
Caused by the bacterium Bordetella pertussis, whooping cough is infamous for its violent coughing fits, which can lead to complications like pneumonia, seizures, and even death, particularly in infants. One nickname for the disease is the 100-days cough because the painful coughing fits can linger for months, even in mild or moderate cases. The disease kills an estimated 200 000 people each year worldwide, most of them infants and children, and survivors of severe illness can be left with brain damage and lung scarring.
While modern vaccines have reduced the toll, their effectiveness wanes over time, with protection only lasting two to five years. Modern pertussis vaccines are acellular, which means they contain portions of the bacteria that train the immune system to recognize the pathogen, including PT.
Recent outbreaks of whooping cough around the world have stunned public health officials. This fall, New York City saw a 169% increase in whooping cough cases since 2023. Cases have increased 500% since 2019. Australia is currently suffering through the largest outbreak of whooping cough since the introduction of the vaccine in the 1940s, with an estimated 41,000 cases reported this year.
Health officials point to missed initial and booster vaccinations as major contributors to the outbreaks.
Overcoming Hesitancy
While advances in fighting pertussis are exciting, they face a dual challenge: overcoming the biological complexity of pertussis and the societal hurdles of vaccine hesitancy. The most effective way to prevent pertussis in vulnerable newborns is for mothers to be vaccinated during pregnancy, which confers protection to the newborn until it is old enough to be vaccinated. According to the CDC, the full vaccination rate against pertussis in kindergarteners is typically over 90% in the US, but under 60% of mothers receive the vaccine during pregnancy. Skepticism about vaccine safety and slow normalization of routine vaccination after the COVID-19 pandemic has led to pockets of under-vaccinated communities and overall low protection of newborns, providing fertile ground for deadly outbreaks. This environment, coupled with the limitations of current vaccines, makes innovation essential.
Co-author Annalee W. Nguyen, a research professor in chemical engineering, emphasized the importance of prevention over treatment. “It’s always easier to prevent disease in a high-risk person,” she said. “Once someone is extremely ill, their immune system isn’t functioning well, and it’s harder to help them recover. Mothers have an incredible opportunity to shield their babies after they are born by getting a pertussis booster vaccination during pregnancy, and parents can continue to protect their families by working with their pediatrician to ensure children and teens are up-to-date on vaccinations.”
By focusing on neutralizing epitopes—areas where antibodies can effectively block the toxin—new vaccines can potentially provide stronger, longer-lasting immunity. This could help bolster public confidence in pertussis vaccines and curb the disease’s resurgence.
An unusual public health policy in Wales may have produced the strongest evidence yet that a vaccine can reduce the risk of dementia. In a new study led by Stanford Medicine, researchers analysing the health records of Welsh older adults discovered that those who received the shingles vaccine were 20% less likely to develop dementia over the next seven years than those who did not receive the vaccine.
The remarkable findings, published April 2 in Nature, support an emerging theory that viruses that affect the nervous system can increase the risk of dementia. If further confirmed, the new findings suggest that a preventive intervention for dementia is already close at hand.
Lifelong infection
Shingles, a viral infection that produces a painful rash, is caused by the same virus that causes chicken pox — varicella-zoster. After people contract chicken pox, usually in childhood, the virus stays dormant in the nerve cells for life. In people who are older or have weakened immune systems, the dormant virus can reactivate and cause shingles.
Dementia affects more than 55 million people worldwide, with an estimated 10 million new cases every year. Decades of dementia research has largely focused on the accumulation of plaques and tangles in the brains of people with Alzheimer’s, the most common form of dementia. But with no breakthroughs in prevention or treatment, some researchers are exploring other avenues — including the role of certain viral infections.
Previous studies based on health records have linked the shingles vaccine with lower dementia rates, but they could not account for a major source of bias: People who are vaccinated also tend to be more health conscious in myriad, difficult-to-measure ways. Behaviors such as diet and exercise, for instance, are known to influence dementia rates, but are not included in health records.
“All these associational studies suffer from the basic problem that people who get vaccinated have different health behaviours than those who don’t,” said Pascal Geldsetzer, MD, PhD, assistant professor of medicine and senior author of the new study. “In general, they’re seen as not being solid enough evidence to make any recommendations on.”
Markus Eyting, PhD, and Min Xie, PhD, postdoctoral scholars in primary care and population health, are the study’s co-lead authors.
A natural experiment
But two years ago, Geldsetzer recognized a fortuitous “natural experiment” in the rollout of the shingles vaccine in Wales that seemed to sidestep the bias. The vaccine used at that time contained a live-attenuated, or weakened, form of the virus.
The vaccination program, which began Sept. 1, 2013, specified that anyone who was 79 on that date was eligible for the vaccine for one year. (People who were 78 would become eligible the next year for one year, and so on.) People who were 80 or older on Sept. 1, 2013, were out of luck — they would never become eligible for the vaccine.
These rules, designed to ration the limited supply of the vaccine, also meant that the slight difference in age between 79- and 80-year-olds made all the difference in who had access to the vaccine. By comparing people who turned 80 just before Sept. 1, 2013, with people who turned 80 just after, the researchers could isolate the effect of being eligible for the vaccine.
The circumstances, well-documented in the country’s health records, were about as close to a randomized controlled trial as you could get without conducting one, Geldsetzer said.
The researchers looked at the health records of more than 280 000 older adults who were 71 to 88 years old and did not have dementia at the start of the vaccination program. They focused their analysis on those closest to either side of the eligibility threshold — comparing people who turned 80 in the week before with those who turned 80 in the week after.
“We know that if you take a thousand people at random born in one week and a thousand people at random born a week later, there shouldn’t be anything different about them on average,” Geldsetzer said. “They are similar to each other apart from this tiny difference in age.”
The same proportion of both groups likely would have wanted to get the vaccine, but only half, those almost 80, were allowed to by the eligibility rules.
“What makes the study so powerful is that it’s essentially like a randomised trial with a control group — those a little bit too old to be eligible for the vaccine — and an intervention group — those just young enough to be eligible,” Geldsetzer said.
Protection against dementia
Over the next seven years, the researchers compared the health outcomes of people closest in age who were eligible and ineligible to receive the vaccine. By factoring in actual vaccination rates — about half of the population who were eligible received the vaccine, compared with almost none of the people who were ineligible — they could derive the effects of receiving the vaccine.
As expected, the vaccine reduced the occurrence over that seven-year period of shingles by about 37% for people who received the vaccine, similar to what had been found in clinical trials of the vaccine. (The live-attenuated vaccine’s effectiveness wanes over time.)
This huge protective signal was there, any which way you looked at the data.”
By 2020, one in eight older adults, who were by then 86 and 87, had been diagnosed with dementia. But those who received the shingles vaccine were 20% less likely to develop dementia than the unvaccinated.
“It was a really striking finding,” Geldsetzer said. “This huge protective signal was there, any which way you looked at the data.”
The scientists searched high and low for other variables that might have influenced dementia risk but found the two groups to be indistinguishable in all characteristics. There was no difference in the level of education between the people who were eligible and ineligible, for example. Those who were eligible were not more likely to get other vaccinations or preventive treatments, nor were they less likely to be diagnosed with other common health conditions, such as diabetes, heart disease and cancer.
The only difference was the drop in dementia diagnoses.
“Because of the unique way in which the vaccine was rolled out, bias in the analysis is much less likely than would usually be the case,” Geldsetzer said.
Nevertheless, his team analyzed the data in alternate ways — using different age ranges or looking only at deaths attributed to dementia, for example — but the link between vaccination and lower dementia rates remained.
“The signal in our data was so strong, so clear and so persistent,” he said.
Stronger response in women
In a further finding, the study showed that protection against dementia was much more pronounced in women than in men. This could be due to sex differences in immune response or in the way dementia develops, Geldsetzer said. Women on average have higher antibody responses to vaccination, for example, and shingles is more common in women than in men.
Whether the vaccine protects against dementia by revving up the immune system overall, by specifically reducing reactivations of the virus or by some other mechanism is still unknown.
Also unknown is whether a newer version of the vaccine, which contains only certain proteins from the virus and is more effective at preventing shingles, may have a similar or even greater impact on dementia.
Geldsetzer hopes the new findings will inspire more funding for this line of research.
“At least investing a subset of our resources into investigating these pathways could lead to breakthroughs in terms of treatment and prevention,” he said.
In the past two years, his team has replicated the Wales findings in health records from other countries, including England, Australia, New Zealand and Canada, that had similar rollouts of the vaccine. “We just keep seeing this strong protective signal for dementia in dataset after dataset,” he said.
But Geldsetzer has set his sights on a large, randomized controlled trial, which would provide the strongest proof of cause and effect. Participants would be randomly assigned to receive the live-attenuated vaccine or a placebo shot.
“It would be a very simple, pragmatic trial because we have a one-off intervention that we know is safe,” he said.
Geldsetzer is seeking philanthropic funding for the trial as the live-attenuated vaccine is no longer manufactured by pharmaceutical companies.
And such a trial might not take long to see results. He pointed to a graph of the Wales data tracking the dementia rates of those who were eligible and ineligible for the vaccine. The two curves began to separate in about a year and a half.
The idea that autism is caused by vaccines has recently been revived by Robert F. Kennedy Jr., the presumptive nominee for US Secretary of Health and Human Services, as well as by president-elect Donald Trump. When asked about vaccines at a recent press conference, Trump reportedly said there was “something wrong” with rising autism rates, adding: “We’re going to find out about it.”
From a research perspective, there is little left to discover about vaccines used in long-standing nationwide vaccine programmes, such as diphtheria, tetanus, whooping cough, polio, measles, mumps and rubella. There is strong data from different countries showing that these vaccines do not cause autism or underlie the vast increase in autism diagnosis rates. So why do suspicions that vaccines cause autism remain?
1. Unawareness of evidence
Reliably and accurately communicating research results to the public is difficult. Research results usually stay in small research or clinical communities. Research is rarely accessible and researchers have few incentives to communicate findings outside of their scientific channels.
Popular media is typically superficial and often primarily interested in controversy that generates public attention.
2. Challenges understanding the science
Science is complicated and in medicine there are rarely absolute truths. The public, however, might expect clear consensus or have difficulty grasping the precise nuance of the science and its findings.
Evidence shows that vaccines do not cause autism or are the reason for increasing diagnosis rates. But it is also in the nature of science that it can neither verify nor exclude totally that vaccines contribute to autism in single individuals.
They protect against viruses and bacteria that cause significant levels of death and human suffering. Vaccine programmes thus have a good risk-to-benefit ratio but are not perfect.
3. Doubts of science
The public may have doubts about science and scientists. Science often delivers probabilities and models, not absolute truths.
This might be disappointing or misunderstood as being no better than individual attitudes or opinions. Although not true for vaccines and autism, evidence can be contradictory and difficult to replicate, reinforcing public doubts.
This success has made most diseases invisible in many countries today. The absence of these diseases generates implicit beliefs that vaccinations are unnecessary.
5. Vaccines cause immune reaction
To reach the goal of immunisation, vaccines must cause an immune reaction. Therefore, a transient inconvenient physical reaction is a sign of success, and the logic of vaccination.
This alone might be counterintuitive and feed doubts about vaccinations. Compared to other drugs, only the side-effects are experienced, and the main effect is preventive, not immediately experienced.
6. Parallelism of events
Autism is a neurodevelopmental condition commonly appearing in the first years of life. Initial autistic behaviour may coincide by chance with vaccination time points or follow them and mix with immune reactions.
Making a connection between vaccination and the appearance of autism in these cases is inevitable. But correlation is not causation.
7. Drugs in infancy without an emergency
Ethical issues arise when people make decisions for others regarding drugs or feel coerced to take them. This is particularly true for infancy where parents must consent for their babies.
It can feel intuitively wrong to interfere with nature and invasive to give a series of shots to a fragile human being in early development in the absence of a medical emergency.
8. Actual harms from less-well established vaccines
Benefits and risks cannot be generalised across all vaccines. Vaccines that are part of long-standing vaccination programmes have good evidence to back them, indicating a convincing risk-benefit ratio.
New vaccines are not ensured in the same way. For instance, the swine flu vaccine during the 2009 pandemic is suspected of having caused 1300 cases of narcolepsy in Europe.
We must distinguish between well-established vaccines and those developed within a short period. It seems that necessary discussions around the safety of less well-established vaccines affect trust in established ones.
9. Polarised debate of vaccines
Open societies build on trust, freedom of speech and debate – but also on shared responsibility. Recent years have seen a polarisation of views around many topics, including vaccinations, not at least fuelled by the COVID crisis.
The urgency of the situation and need for solidarity left little space and time for discussion in society and marginalised or stigmatised even moderate sceptics. The latter has surely harmed trust in vaccines more generally.
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.
