The study explored whether prophylactic (shortly before or after exposure) administration of the recently developed clinical candidate GHP-88310 (described in Science Advances²), a broad-spectrum inhibitor of the viral polymerase, prevents virus transmission through close contact or through the air. The results demonstrate that GHP-88310 efficiently blocks both forms of viral spread. In addition, the study showed that treatment of infected animals shortened the time period in which infected animals could transmit the virus.

“Silencing measles outbreaks quickly is essential to reestablish control over the virus,” said senior author Richard Plemper, a Regents’ Professor and director of the CTAR. “This study follows our recent development of the drug candidate GHP-88310. It demonstrates that the drug is suitable to augment traditional ring vaccination against measles.”

Since 2025, measles has reemerged in the United States with thousands of cases across multiple states, hundreds of hospitalizations and three confirmed deaths. Large outbreaks in Canada and Mexico with multiple deaths have challenged the measles elimination status of North America.

“We were very excited to see that GHP-88310 given by mouth completely prevented airborne transmission in our ferret model of measles,” said first author Carolin Lieber, a senior postdoctoral fellow in the Plemper lab. “This finding is unprecedented for a viral polymerase inhibitor and demonstrates the extraordinary antiviral potency of this drug.”

To explore relevant conditions of viral transmission, the researchers developed a system that allowed them to pair infected and uninfected animals in direct physical contact or shared airspace, each under controlled environmental parameters.

“We designed the study to recapitulate viral spread between people with direct contact, for instance in a household, and between more distant social contacts, for example in classrooms or other indoor settings that bring people into proximity without direct interaction,” said Plemper. “In addition to this prophylactic benefit, GHP-88310 used therapeutically shortened the duration of disease in our model. If equally applicable to human hosts, it may shorten the severe social and economic burden of prolonged quarantine of patients and further aid outbreak management.”

The investigators are now readying GHP-88310 for formal clinical testing.

Additional authors of the study include Josef Wolf, Claire Ruckel and Lauren Harrison of the Center for Translational Antiviral Research in the Institute for Biomedical Sciences at Georgia State.

The study was funded by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH).

To read the studies, visit

¹ DOI 10.1038/s41564-026-02419-y. Once published online, it will be available at URL: https://www.nature.com/articles/s41564-026-02419-y

² DOI: 10.1126/sciadv.aef1594. URL: https://www.science.org/doi/10.1126/sciadv.aef1594?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

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Research led by City St George’s, University of London and University of Oxford developed the first global framework that estimates how many and which type of antibiotics each country needs to treat their infections.

Antibiotics are grouped by the World Health Organization (WHO) into three categories, known as the “AWaRe” system:

• ‘Access’ antibiotics are used for most common infections and have a lower resistance risk.
• ‘Watch’ antibiotics have a broader spectrum, are used for specific infections and come with higher safety and resistance concerns.
• ‘Reserve’ antibiotics are last resort antibiotics used to treat multi-drug resistant infections.

In 2024, world leaders at the United Nations agreed that at least 70% of antibiotic use worldwide should come from the Access group by 2030. However, no method previously existed to determine the right balance of antibiotics for any individual country.

To address this, researchers analysed global data from 186 countries, territories and areas (CTAs), representing 99.8% of the global population. They grouped these countries into ‘peer groups’ based on similar infection burdens, resistance patterns, socioeconomic characteristics and healthcare access.

Within each group, countries with the lowest antibiotic use and the fewest infection-related deaths were used as benchmarks to determine what optimal antibiotic use should look like for similar countries. They then estimated optimal levels of Access, Watch and Reserve antibiotics required in each setting based on infection and resistance burdens.

The team calculated that in 2019, around 43 billion days of antibiotics were needed globally, averaging out to roughly one antibiotic course per person per year, to treat all bacterial infections appropriately. They found that 77% of global antibiotic use should be Access antibiotics, suggesting the UN’s 70% target is reasonable.

Although higher-income countries currently use the most Watch and Reserve antibiotics, the study estimates that more than 80% of the world’s optimal need for these medicines lies in lower-income countries, where infectious disease and antimicrobial resistance burdens are highest.

The researchers then compared their estimates with real-world antibiotic use data from 67 countries where this data was available. Nearly three-quarters (72%) of countries analysed were using more antibiotics in total than needed, and almost every country (99%) prescribed too many Watch antibiotics, which contribute the most to antibiotic resistance. Worryingly, 60% of countries were still using antibiotics that the WHO considers should no longer be prescribed.

At the same time, 42% of countries were using fewer Access antibiotics than estimated optimal levels, and more than half (52%) were not using enough Reserve antibiotics than estimated to be needed. This means patients with life-threatening drug-resistant infections might not be receiving the specific treatments they need.

The findings suggest that many countries could improve antibiotic use by reducing unnecessary Watch antibiotic prescribing while increasing access to essential Access antibiotics, and ensuring availability of Reserve antibiotics for patients with highly resistant infections.

Aislinn Cook, lead author and Senior Research Fellow in Infectious Diseases Epidemiology at City St George’s, University of London, and DPhil student at Nuffield Department of Primary Care Health Sciences, University of Oxford said:

“Our findings show the world faces a double challenge – while some antibiotics are being overused, millions of people may still lack access to the medicines they need to treat their infections.

“We have developed the first practical way for countries to estimate how much of each type of antibiotic their populations need based on infection burden and antibiotic resistance. This framework can help move the conversation beyond measuring antibiotic consumption to matching antibiotic use with public health need. This can support countries to develop more targeted policies to reduce overuse while ensuring sustainable access to effective antibiotics.”

The team emphasise that improving access to antibiotics for the most vulnerable populations will require action at both local and national levels. This includes ensuring that quality-assured antibiotics are available and affordable in frontline healthcare settings, while national governments ensure that the right antibiotics are procured and supplied in sufficient quantities. The researchers also highlight the need for better monitoring of antibiotic use to identify areas of overuse and underuse, and for national targets based on local data that align antibiotic use more closely with public health and clinical need.

Dr Koen Pouwels, Associate Professor in Health Economics, Nuffield Department of Primary Care Health Sciences, University of Oxford and co-author, said:

“Global targets such as aiming for 70% of antibiotic use to come from the WHO Access group are an important starting point, but they cannot tell countries how much of each AWaRe antibiotic group they actually need.

“By providing country-specific benchmarks, our work gives policymakers a practical way to move beyond percentage targets and make better-informed decisions about reducing overuse, improving access and strengthening antibiotic stewardship. Importantly, these benchmarks can become more ambitious over time if countries reduce infection burden, even in the face of demographic change.”

The study was funded by the Wellcome Trust.

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The drugs are effective but don’t eliminate the virus; HIV remains hidden in “reservoirs” throughout the body, ready to reactivate if treatment stops.

But researchers at Case Western Reserve University, in collaboration with the University of Pittsburgh, have made a significant breakthrough in HIV treatment. They’ve shown that NK (Natural Killer) cells—specialized immune cells that naturally target virus-infected and tumor cells—can be enhanced to better fight HIV infections.

Their findings were recently published in mBio, the scientific journal for the American Society of Microbiology.

“NK cell immunotherapy is already being used for cancer therapy, and the data from those studies provides a great foundation for translation of this approach to an HIV cure strategy,” said Mary Ann Checkley-Luttge, a senior research associate at the Case Western Reserve School of Medicine, who led the study. “We are hoping that NK cell immunotherapy can help reduce the reservoir enough to allow long-term immunological control of HIV without ART.”

Checkley-Luttge works in the lab of Jonathan Karn, a professor at the School of Medicine and pioneer in HIV research as director of the Case Center for AIDS Research.

The research team discovered that NK cells taken from HIV-positive patients can be expanded and enhanced in the lab to more effectively target and reduce these viral reservoirs.

This discovery marks a significant step toward long-term HIV remission by enhancing the body’s immune system. The approach could enable people with HIV to control the virus without lifelong dependence on daily antiretroviral medications.

The groundwork for such a discovery was supported by Case Western Reserve’s long-standing interdisciplinary collaboration and robust HIV research infrastructure. The School of Medicine houses a National Institutes of Health-designated Center for AIDS Research founded more than 30 years ago, and the Center for Excellence on the Impact of Substance Use on HIV, providing access to cutting-edge technologies essential for high-impact HIV research.

“Our team’s next goals are to test whether lab-enhanced NK cells can work as ‘off-the-shelf’ therapy,” said Karn, Distinguished University Professor and chair of the Department of Molecular Biology and Microbiology. “We plan to conduct studies using advanced animal models that closely mimic HIV infection in humans and then work toward clinical trials in the next two years to test this approach in people living with HIV.”

The research was made possible through blood donations from people living with HIV and represents a collaborative effort between patients, researchers and institutions working toward better HIV treatments.

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Fungal diseases cause huge economic and health burdens. Antifungal agents (fungicides) are widely used in agriculture and medicine to combat their spread. However, developing new compounds to kill harmful fungi in plants (pesticides) may increase fungal resistance to treatments in humans and animals.

“Antimicrobial resistant pathogens are a constant reminder for us to use agents judiciously,” Thompson said. “We have learned that the widespread use of antibiotics for livestock resulted in the rapid development of resistance to antibacterials. We have similar concerns regarding the use of antifungals in the environment.”

Thompson is the article’s lead author. He is a professor at the UC Davis School of Medicine in the Department of Internal Medicine, Division of Infectious Diseases, and the Department of Medical Microbiology and Immunology.

A One Health approach proposes a more holistic view to health. It emphasizes how changes in one area — like human activity, animal health, or the environment — can have ripple effects across all three.

About antifungal resistance

Changes in the climate and the wind patterns can help spread pathogens like fungi. Also, human travelers, migrating animals and the movement of contaminated items can carry pathogens to new areas.

In the last few decades, there has been a rapid increase in fungus types that cause severe infections in humans. One example of difficult-to-treat fungus is Candida auris (C. auris).

“Fungi have similar cellular machinery to that of humans. This is why medications that kill fungi like C. auris often have side effects for people. With few antifungals to choose from during clinical care, preventing resistance is of paramount importance,” Thompson explained.

Coordinated pesticide development and use

Resistance to treatments is highly linked to the amount of each agent used, the authors wrote. They called for coordinated global regulation to slow the development of resistance to new antimicrobial agents.

“There is a need for a shared antimicrobial approval process that includes a thorough assessment of potential impacts on the environment and human and animal health. This is especially true before any new large-scale environmental and agricultural pesticide use,” Desai said. She is an associate professor in the Department of Internal Medicine.

Their report also noted the foundation of The Interagency Drug and Pesticide Resistance and Efficacy Workgroup, a new entity under The U.S. Environmental Protection Agency. It is tasked with providing input on upcoming compounds proposed for registration, including potential effects on medical practice. The authors said similar efforts are needed on a global scale.

They noted that shared decision-making among national and global regulatory agencies would be cost-effective. It might help avoid the more expensive and riskier prospects of the rapid spread of resistant pathogens.

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University of Vienna

Extremely premature infants are at a high risk for brain damage. Researchers have now found possible targets for the early treatment of such damage outside the brain: Bacteria in the gut of premature infants may play a key role. The research team found that the overgrowth of the gastrointestinal tract with the bacterium Klebsiella is associated with an increased presence of certain immune cells and the development of neurological damage in premature babies.

Complex interplay: the gut-immune-brain axis

The early development of the gut, the brain and the immune system are closely interrelated. Researchers refer to this as the gut-immune-brain axis. Bacteria in the gut cooperate with the immune system, which in turn monitors gut microbes and develops appropriate responses to them. In addition, the gut is in contact with the brain via the vagus nerve as well as via the immune system. “We investigated the role this axis plays in the brain development of extreme preterm infants,” says the first author of the study, David Seki. “The microorganisms of the gut microbiome — which is a vital collection of hundreds of species of bacteria, fungi, viruses and other microbes — are in equilibrium in healthy people. However, especially in premature babies, whose immune system and microbiome have not been able to develop fully, shifts are quite likely to occur. These shifts may result in negative effects on the brain,” explains the microbiologist and immunologist.

Patterns in the microbiome provide clues to brain damage

“In fact, we have been able to identify certain patterns in the microbiome and immune response that are clearly linked to the progression and severity of brain injury,” adds David Berry, microbiologist and head of the research group at the Centre for Microbiology and Environmental Systems Science (CMESS) at the University of Vienna as well as Operational Director of the Joint Microbiome Facility of the Medical University of Vienna and University of Vienna. “Crucially, such patterns often show up prior to changes in the brain. This suggests a critical time window during which brain damage of extremely premature infants may be prevented from worsening or even avoided.”

Comprehensive study of the development of extremely premature infants

Starting points for the development of appropriate therapies are provided by the biomarkers that the interdisciplinary team was able to identify. “Our data show that excessive growth of the bacterium Klebsiella and the associated elevated ??-T-cell levels can apparently exacerbate brain damage,” explains Lukas Wisgrill, Neonatologist from the Division of Neonatology, Pediatric Intensive Care Medicine and Neuropediatrics at the Department of Pediatric and Adolescent Medicine at the Medical University of Vienna. “We were able to track down these patterns because, for a very specific group of newborns, for the first time we explored in detail how the gut microbiome, the immune system and the brain develop and how they interact in this process,” he adds. The study monitored a total of 60 premature infants, born before 28 weeks gestation and weighing less than 1 kilogram, for several weeks or even months. Using state-of-the-art methods — the team examined the microbiome using 16S rRNA gene sequencing, among other methods — the researchers analysed blood and stool samples, brain wave recordings (e.g. aEEG) and MRI images of the infants’ brains.

Research continues with two studies

The study, which is an inter-university clusterproject under the joint leadership by Angelika Berger (Medical University of Vienna) and David Berry (University of Vienna), is the starting point for a research project that will investigate the microbiome and its significance for the neurological development of prematurely born children even more thoroughly. In addition, the researchers will continue to follow the children of the initial study. “How the children’s motoric and cognitive skills develop only becomes apparent over several years,” explains Angelika Berger. “We aim to understand how this very early development of the gut-immune-brain axis plays out in the long term. ” The most important cooperation partners for the project are already on board: “The children’s parents have supported us in the study with great interest and openness,” says David Seki. “Ultimately, this is the only reason we were able to gain these important insights. We are very grateful for that.”

Journal Reference:

1. David Seki, Margareta Mayer, Bela Hausmann, Petra Pjevac, Vito Giordano, Katharina Goeral, Lukas Unterasinger, Katrin Klebermaß-Schrehof, Kim De Paepe, Tom Van de Wiele, Andreas Spittler, Gregor Kasprian, Benedikt Warth, Angelika Berger, David Berry, Lukas Wisgrill. Aberrant gut-microbiota-immune-brain axis development in premature neonates with brain damage. Cell Host & Microbe, 2021; DOI: 10.1016/j.chom.2021.08.004

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In a clinical trial, 36 healthy adults were randomly assigned to a 10-week diet that included either fermented or high-fiber foods. The two diets resulted in different effects on the gut microbiome and the immune system.

Eating foods such as yogurt, kefir, fermented cottage cheese, kimchi and other fermented vegetables, vegetable brine drinks, and kombucha tea led to an increase in overall microbial diversity, with stronger effects from larger servings. “This is a stunning finding,” said Justin Sonnenburg, PhD, an associate professor of microbiology and immunology. “It provides one of the first examples of how a simple change in diet can reproducibly remodel the microbiota across a cohort of healthy adults.”

In addition, four types of immune cells showed less activation in the fermented-food group. The levels of 19 inflammatory proteins measured in blood samples also decreased. One of these proteins, interleukin 6, has been linked to conditions such as rheumatoid arthritis, Type 2 diabetes and chronic stress.

“Microbiota-targeted diets can change immune status, providing a promising avenue for decreasing inflammation in healthy adults,” said Christopher Gardner, PhD, the Rehnborg Farquhar Professor and director of nutrition studies at the Stanford Prevention Research Center. “This finding was consistent across all participants in the study who were assigned to the higher fermented food group.”

Microbe diversity stable in fiber-rich diet

By contrast, none of these 19 inflammatory proteins decreased in participants assigned to a high-fiber diet rich in legumes, seeds, whole grains, nuts, vegetables and fruits. On average, the diversity of their gut microbes also remained stable. “We expected high fiber to have a more universally beneficial effect and increase microbiota diversity,” said Erica Sonnenburg, PhD, a senior research scientist in basic life sciences, microbiology and immunology. “The data suggest that increased fiber intake alone over a short time period is insufficient to increase microbiota diversity.”

The study will be published online July 12 in Cell. Justin and Erica Sonnenburg and Christopher Gardner are co-senior authors. The lead authors are Hannah Wastyk, a PhD student in bioengineering, and former postdoctoral scholar Gabriela Fragiadakis, PhD, who is now an assistant professor of medicine at UC-San Francisco.

A wide body of evidence has demonstrated that diet shapes the gut microbiome, which can affect the immune system and overall health. According to Gardner, low microbiome diversity has been linked to obesity and diabetes.

“We wanted to conduct a proof-of-concept study that could test whether microbiota-targeted food could be an avenue for combatting the overwhelming rise in chronic inflammatory diseases,” Gardner said.

The researchers focused on fiber and fermented foods due to previous reports of their potential health benefits. While high-fiber diets have been associated with lower rates of mortality, the consumption of fermented foods can help with weight maintenance and may decrease the risk of diabetes, cancer and cardiovascular disease.

The researchers analyzed blood and stool samples collected during a three-week pre-trial period, the 10 weeks of the diet, and a four-week period after the diet when the participants ate as they chose.

The findings paint a nuanced picture of the influence of diet on gut microbes and immune status. On one hand, those who increased their consumption of fermented foods showed similar effects on their microbiome diversity and inflammatory markers, consistent with prior research showing that short-term changes in diet can rapidly alter the gut microbiome. On the other hand, the limited change in the microbiome within the high-fiber group dovetails with the researchers’ previous reports of a general resilience of the human microbiome over short time periods.

Designing a suite of dietary and microbial strategies

The results also showed that greater fiber intake led to more carbohydrates in stool samples, pointing to incomplete fiber degradation by gut microbes. These findings are consistent with other research suggesting that the microbiome of people living in the industrialized world is depleted of fiber-degrading microbes.

“It is possible that a longer intervention would have allowed for the microbiota to adequately adapt to the increase in fiber consumption,” Erica Sonnenburg said. “Alternatively, the deliberate introduction of fiber-consuming microbes may be required to increase the microbiota’s capacity to break down the carbohydrates.”

In addition to exploring these possibilities, the researchers plan to conduct studies in mice to investigate the molecular mechanisms by which diets alter the microbiome and reduce inflammatory proteins. They also aim to test whether high-fiber and fermented foods synergize to influence the microbiome and immune system of humans. Another goal is to examine whether the consumption of fermented food decreases inflammation or improves other health markers in patients with immunological and metabolic diseases, and in pregnant women and older individuals.

“There are many more ways to target the microbiome with food and supplements, and we hope to continue to investigate how different diets, probiotics and prebiotics impact the microbiome and health in different groups,” Justin Sonnenburg said.

Journal Reference:

1. Hannah C. Wastyk, Gabriela K. Fragiadakis, Dalia Perelman, Dylan Dahan, Bryan D. Merrill, Feiqiao B. Yu, Madeline Topf, Carlos G. Gonzalez, William Van Treuren, Shuo Han, Jennifer L. Robinson, Joshua E. Elias, Erica D. Sonnenburg, Christopher D. Gardner, Justin L. Sonnenburg. Gut-microbiota-targeted diets modulate human immune status. Cell, 2021; DOI: 1016/j.cell.2021.06.019

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Research presented by Dr Ana R. Freitas, and colleagues from UCIBIO, Faculty of Pharmacy, University of Porto, Portugal, showed that dog food from supermarkets and pet shops was a major source of antibiotic-resistant bacteria, making it an international public health risk.

With some of the multidrug-resistant bacteria in raw dog food identical to those found in hospital patients in several different European countries, the researchers say the trend for feeding dogs raw food may be fuelling the spread of antibiotic resistant-bacteria.

Drug-resistant infections kill an estimated 700,000 people a year globally and, with the figure projected to rise to 10 million by 2050 if no action is taken, the World Health Organisation (WHO) classes antibiotic resistance as one of the greatest public health threats facing humanity.

A total of 55 samples of dog food (22 wet, 8 dry, 4 semi-wet, 7 treats and 14 raw-frozen) from 25 brands available nationally and internationally were included in the study. The raw-frozen foods included duck, salmon, turkey, chicken, lamb, goose, beef and vegetables.

Thirty samples (54%) contained Enterococci. More than 40% of the Enterococci were resistant to the antibiotics erythromycin, tetracycline, quinupristin-dalfopristin, streptomycin, gentamicin, chloramphenicol, ampicillin or ciprofloxacin. There was also resistance to vancomycin and teicoplanin (2% each) and 23% of the enterococci were resistant to linezolid, a last-resort antibiotic. All of the raw dog food samples contained multidrug-resistant Enterococci, including bacteria resistant to linezolid. In contrast, only three of the non-raw samples contained multidrug- resistant bacteria.

Genetic sequencing revealed that some of the multi-drug resistant bacteria in the raw dog food were identical to bacteria isolated from hospital patients in the UK, Germany and the Netherlands. Genetically identical bacteria have also been found in farm animals and wastewater in the UK.

The researchers concluded that dog food is a source of bacteria that are resistant to last-resort antibiotics and could potentially spread to humans. Dog food, they add, could be an overlooked driver of antibiotic resistance globally.

Dr Freitas said: “The close contact of humans with dogs and the commercialisation of the studied brands in different countries poses an international public health risk.  European authorities must raise awareness about the potential health risks when feeding raw diets to pets and the manufacture of dog food, including ingredient selection and hygiene practices, must be reviewed. Dog owners should always wash their hands with soap and water right after handling pet food and after picking up faeces.”

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Research presented at this year’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) taking place online (9-12 July) shows that covering high-touch (the most regularly touched) surfaces in hospitals with silver-impregnated foil could significantly reduce levels of contamination by clinically important bacterial pathogens.

The study by Professor Andreas Widmer and colleagues at the University Hospital Basel, Basel, Switzerland, evaluated the antimicrobial effectiveness of a polyvinyl chloride (PVC) foil containing an integrated silver-based agent containing 2% silver ions.

The hospital environment has increasingly been recognised as having critical importance when formulating infection control measures as evidence has increased of the role it plays as a source of bacterial transmission and subsequent hospital-acquired infections. Regular cleaning and disinfection have been proposed as an option for lowering infection risk, however performing this to the required standard is a time and resource-intensive process.

An alternative approach is to use auto-disinfecting surfaces which would make it difficult for pathogens to survive and would require less thorough cleaning to achieve a safe environment in patient rooms. In this study a silver-impregnated PVC foil was applied to high-touch surfaces in patient rooms where contamination levels of bacterial pathogens were anticipated to be high.

The researchers found that contamination levels on foil-covered surfaces were significantly lower than on those without the covering. Overall, mean germ numbers were reduced by more than 60 times, while the median bioburden on untreated control surfaces was more than 3 times higher than on the antimicrobial foil. The large difference between mean and median relates to the large biological variability of germ density on the different types of surfaces.

The team also discovered that clinically important bacteria – in particular Enterococci – were significantly less likely to be present on foil-covered surfaces, and the antimicrobial effects were still present six months later.

The authors conclude: “A foil containing an integrated silver-based agent effectively decreases the load of clinically important disease-causing bacteria over a six-month study period.”

They add: “Auto-disinfectant foils or similar antimicrobially equipped surfaces might help prevent transmission, in particular of Gram-positive pathogens from the environment. Many studies confirm rapid recolonization (reinfection) of hospital surfaces even after vigorous disinfection. Therefore, such auto-disinfectant foils could be desirable in certain healthcare areas such as transplant units or also during outbreaks such as the SARS-CoV-2 pandemic we are currently experiencing. Further research should be extended to the antiviral activity of such surfaces, as this silver-impregnated PVC foil has been found to work in experiments against another type of coronavirus: human coronavirus HCov-229E.”

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Each of these cells carries a unique T cell receptor on the surface that can recognize certain antigens. However, only very few T cell receptors match a given viral the antigen.

To bring the infection under control and maximize the defenses against the virus, these few antigen-specific T cells start dividing rapidly and develop into effector T cells. These kill virus-infected host cells and then die off themselves once the infection is cleared. Some of these short-lived effector cells – according to the generally accepted theory – turn into memory T cells, which persist in the organism long term. In case the same pathogen enters the body again, memory T cells are already present and ready to fight the invader more swiftly and effectively than during the first encounter.

Memory cells and their origin

“Prevailing scientific opinion says that activated T cells first become effector cells and only then gradually develop into memory cells,” says Dr. Veit Buchholz, a specialist in microbiology and working group leader at the Institute for Medical Microbiology, Immunology and Hygiene at TUM. “In our view, however, that isn’t the case. It would mean that the more effector cells are formed after contact with the pathogen, the more numerous the memory cells would become.” However, Buchholz and his colleagues observed a different course of events and have now published their results in the journal Nature Immunology.

“We investigated the antiviral immune responses resulting from individual activated T cells in mice and traced the lineage of the ensuing memory cells using single-cell fate mapping,” reports first author Dr. Simon Grassmann. “Based on these experiments, we were able to show that certain ‘T cell families’ descended from individual cells form up to 1000 times more ‘memory’ than others. However, these long-term dominating T cell families only contributed little to the magnitude of the initial immune response, which was dominated by effector cells derived from other shorter-lived T cell families.”

At the level of individual cells, it therefore became evident that development of effector and memory cells segregates at a much earlier stage than previously believed: “Already in the first week after the confrontation with the pathogen, we saw major differences in the transcriptomes of the detected T cell families,” says Lorenz Mihatsch, also a first author of the study. “Normally at this time of the immune response CD8+ T cells are enriched in molecules that help to kill virus infected cells. However, we found no indication of these cytolytic molecules in the long-term dominating T cell families. Instead, they were already geared exclusively towards memory development at this early stage.”

Optimization of vaccines

These results could help to improve vaccine development in the future, says Veit Buchholz: “To generate an optimal immune response through vaccination, the body needs to produce as many memory cells as possible. For that purpose, it is important to have a precise understanding of how individual T cells are programmed.” Buchholz’s study might also prove useful in helping to recognize sooner whether a new vaccine is effective. “To determine the long-term strength of an immune response, it could be helpful to measure the number of memory precursors within a few days of administering a vaccine,” says Buchholz.

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