Metabolic health (normal blood pressure, blood sugar and cholesterol levels, among other factors) influences the effectiveness of influenza vaccinations. Vaccination is known to be less effective in people with obesity compared to those with a healthier body mass index (BMI), but St. Jude Children's Research Hospital scientists have found it is not obesity itself, but instead metabolic dysfunction, which makes the difference. In a study published today in Nature Microbiology, the researchers found switching obese mice to a healthy diet before flu vaccination, but not after, completely protected the models from a lethal dose of flu, despite BMI.
We found that the vaccines worked effectively if at the time of vaccination an animal is metabolically healthy. And the opposite was also true: Regardless of what the mice looked like on the outside, if they had metabolic dysfunction, the vaccines did not work as well."
Stacey Schultz-Cherry, PhD, corresponding author, St. JudeDepartment of Host-Microbe InteractionsandCenter of Excellence for Influenza Research and Responseco-director
Prior research has shown that when exposed to influenza virus, even after vaccination, 100% of obese mice succumbed to disease. Contrary to the scientists' original expectations, when mice who were vaccinated while obese returned to a healthy weight, outcomes did not improve. These now outwardly healthy mice still all succumbed to disease when exposed to the real virus. Only switching to a healthy diet four weeks before vaccination improved survival, with drastic effect, despite high BMI.
"We were excited to see this effect because mice with obesity are so susceptible to severe disease and succumbing to the infection," Schultz-Cherry said. "Getting 100% survival with the vaccine where we had only seen 0% survival was impressive." The improved survival suggests the researchers have discovered a greater underlying principle determining influenza vaccine efficacy.
While studying how metabolic function influences influenza vaccine responses, the scientists found that poor metabolic health causes immune system dysfunction. T cells, the primary immune cells involved in anti-viral responses, failed to act in animals that had been in an unhealthy metabolic state at the time of vaccination, even during later viral exposure. Even when the animals ate a healthy diet after vaccination and maintained a normal BMI, the anti-flu T cells were "frozen" in that dysfunctional state.
However, a healthy diet before vaccination improved T-cell function, which resulted in a robust anti-flu response during later exposure.
"The T cells were better able to do their job in the metabolically healthy mice at the time of vaccination," Schultz-Cherry said. "It wasn't a matter of the numbers of them or the types of them. It was their functional activity. There were plenty of them in the lungs, not working. The healthy diet switched them from not working to functioning properly, but only if the switch occurred before vaccination."
The earlier healthy diet also improved inflammation. Pro-inflammatory cytokines are upregulated in obese animals. Schultz-Cherry's team found that models also returned to a lower basal cytokine level when switched to a healthy diet before vaccination.
"A healthy diet lowered some of the systemic meta-inflammation in these animals, and they regained some of the epithelial innate immune responses," said Schultz-Cherry. "We started seeing better signaling of things like interferons, which we know is problematic in obesity and in general saw the immune system starting to function the way that it should."
"What we found and are emphasizing is that it's not the phenotype of obesity that matters; it's really about metabolic health," Schultz-Cherry said. "It's metabolic health at that moment of vaccination that really makes a difference."
The study was restricted to mice, but it does open research opportunities to improve influenza vaccine efficacy in humans. The findings suggest methods of improving metabolic health may also improve subsequent influenza vaccinations. Given the recent introduction of metabolic improvement drugs, especially glucagon-like peptide 1 (GLP-1) agonists, there may be potential for a cooperative effect.
"We don't know for sure, but if the outcome of using GLP-1 drugs is weight loss and improved metabolic health, we would hypothesize that it will help," Schultz-Cherry said. "But we do know that we can do better protecting our vulnerable populations, and this study is a start for understanding how."
The study's co-first authors are Rebekah Honce, formerly of St. Jude, and Ana Vazquez-Pagan, formerly of the St. Jude Graduate School of Biomedical Sciences.
The study's other authors are R. Chris Skinner, University of Vermont, Brandi Livingston, Alexandra Mandarano, Benjamin Wilander, Sean Cherry, Virginia Hargest, Bridgett Sharp, Pamela Brigleb, Ericka Kirkpatrick Roubidoux, Lee-Ann Van de Velde, Maureen McGargill and Paul Thomas, St. Jude.
The study was supported by grants and contracts from the National Institute of Allergy and Infectious Diseases (HHSN27220140006C, 75N93019C00052, 75N93021C00016, F31AI161986, R01 AI140766-03 and 32AI106700-07) and ALSAC, the fundraising and awareness organization of St. Jude.
Source:
Journal reference:
Honce, R., et al. (2024). Diet switch pre-vaccination improves immune response and metabolic status in formerly obese mice.Nature Microbiology. doi.org/10.1038/s41564-024-01677-y.
Researchers from St Georges, University of London have identified key barriers to vaccine uptake for whooping cough, flu and Covid-19 in pregnant women, and outline recommendations for addressing vaccine hesitancy. The results are from the first review of its kind and published today in the journalPLOS ONE.
Pregnant women are at increased risk of viral infections due to changes in their immune system during pregnancy. Vaccinations particularly for influenza (flu), pertussis (whooping cough) and Covid-19 are therefore highly recommended. If pregnant women choose not to have these vaccines, they not only put themselves at increased risk of disease, hospitalization and death, but also prevent their baby from having increased protection from birth.
Despite the NHS and the WHO strongly recommending these vaccines in pregnancy, uptake remains low in the UK with only 51% of pregnant women having two doses of Covid-19 vaccine, 60% having the whooping cough vaccine and just 30% taking the flu jab.
To better identify the main barriers and facilitators for vaccine uptake in pregnant women, researchers carried out the first systematic review of qualitative interview-based studies published between 2012 and 2022 in high-income countries with established vaccination programmes throughout pregnancy. Countries included the UK, Australia, New Zealand and the USA.
Their search identified 2,681 relevant articles, of which 28 peer-reviewed articles covering 1,573 women were included in the review. The majority of studies (78%) focused on flu and whooping cough.
The review revealed that the main barriers to vaccine uptake in pregnant women included concerns about vaccine safety and efficacy, a lack of knowledge about the benefits and necessity of vaccines, fear of adverse effects to themselves and their baby, poor understanding in how severe these diseases can be without vaccination, lack of endorsement by healthcare professionals and barriers to physically accessing vaccines whilst juggling other health appointments and priorities.
Now, Dr Mohammad Razai and his team have laid out key recommendations they hope will be embedded into public health strategies. They centre on five Cs confidence, complacency, convenience, communication and context. More specifically, their calls include [1]:
Vaccine hesitancy remains very high among pregnant women, but vaccination against whooping cough, flu and Covid-19 in pregnancy is crucial. In this day and age, people should not be hospitalized or even die from diseases that are preventable by safe and effective vaccines.
Our work has collated the views of over 1,000 pregnant women, and we hope that the key recommendations weve set-out will be applied to public health strategies in the UK and further afield. We believe these are vital to tackle vaccine hesitancy and increase protection of mothers-to-be and their children.
Dr Mohammad Razai, Lead researcher and Clinical Academic GP, Population Health Research Institute atSt Georges, University of London
The team are now developing community interventions to boost vaccination rates among women with low uptake. This involves training midwives to counsel pregnant women on vaccinations and sharing real-life stories to empower informed decision-making.
Dr Razais In-practice Fellowship was funded by the National Institute for Health and Care Research (NIHR).
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Posted: April 18, 2024
The World Health Organization (WHO) and around 500 experts have agreed for the first time what it means for a disease to spread through the air, in a bid to avoid the confusion early in the COVID-19 pandemic that some scientists have said cost lives.
The Geneva-based U.N. health agency released a technical document on the topic on Thursday. It said it was the first step towardworking out how to better prevent this kind of transmission, both for existing diseases like measles and for future pandemic threats.
The document concludes that the descriptor "through the air" can be used for infectious diseases where the main type of transmission involves the pathogen travelling through the air or being suspended in the air, in line with other terms such as "waterborne" diseases, which are understood across disciplines and by the public.
Almost 500 experts contributed to the definition, including physicists, public health professionals and engineers, many of whom disagreed bitterly over the topic in the past.
Agencies have historically required high levels of proof before calling diseases airborne, which required very stringent containment measures; the new definition says the risk of exposure and severity of disease should also be considered.
WATCH | Airborne transmission and COVID-19:
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Past disagreements also centred on whether infectious particles were "droplets" or "aerosols" based on size, which the new definition moves away from.
During the early days of COVID in 2020, around 200 aerosol scientists publicly complained that the WHO had failed to warn people of the risk that the virus could spread through the air. This led to an overemphasis on measures like handwashing to stop the virus, rather than focusing on ventilation, they said.
By July 2020, the agency said there was "evidence emerging" of airborne spread, but its then chief scientist Soumya Swaminathan,who began the process to get a definition, later said the WHO should have been more forceful "much earlier."
Her successor, Jeremy Farrar, said in an interview that the new definition was about more than COVID, but he added that at the beginning of the pandemic there was a lack of evidence available and experts including the WHO acted in "good faith." At that time, he was head of the Wellcome Trust charity and advised the British government on the pandemic.
Farrar said getting the definition agreed upon among experts from all disciplines would allow discussions to begin about issues such as ventilation in many different settings, from hospitals to schools.
He compared it to the realization that blood-borne viruses like HIV or hepatitis B could be spread by medics not wearing gloves during procedures.
"When I started out, medical students, nurses, doctors, none of us wore gloves to take blood," he told Reuters. "Now it is unthinkable that you wouldn'twear gloves. But that came because everyone agreed on what the issue was, they agreed on the terminology.[The change in practice] came later."
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An initial zero draft that circulated more than a year ago now appears to have been diluted, or as the Lancet medical journal notes, filled with platitudes, caveats and the term where appropriate.
In early 2023, the zero draft contained details on building an equitable global health security ecosystem. It included recommendations on supply chain resilience for products needed to ensure health security.
But now, with the World Health Assembly meeting just weeks away, differences between the rich Western countries and the developing world seem wider than ever. When the latest round of negotiations ended inconclusively on March 28, the Fox News channel in the United States went on the attack with a story highlighting critics who say the Biden administration was selling out US sovereignty.
The foundation insists the agreement should be rejected in its current draft form, and that even an improved draft would need to be submitted to the US Senate for advice and consent.
In the US Congress, Brad Wenstrup, the Republican chair of the US House Select Subcommittee on the Coronavirus Pandemic, insisted the treaty must not violate international sovereignty or infringe upon the rights of the American people or the intellectual property of the US.
Voicing the concerns of the global science community, a Lancet editorial retorted that such approaches were shameful, unjust and inequitable, saying that there is a need for high-income countries and private companies to behave fairly, [and] that they do not stockpile millions of doses of vaccines or refuse to share life-saving knowledge and products.
The editorial complained that, under the current draft treaty, the WHO would only have access to 20 per cent of the pandemic-related products for distribution based on public health risks and needs, leaving 80 per cent of medicines and vaccines prey to the international scramble that in Covid-19 saw vital health technologies sold to the highest bidder.
Ensuring equitable access is not an act of kindness or charity, it insisted: It is an act of science, an act of security and an act of self-interest Ultimately it is the politicians of G7 countries who must put aside vested industry interests and finally understand that in a pandemic it is not possible to protect only your own citizens.
It is of course possible that, by some miracle of pragmatism, a meaningful pandemic treaty will emerge from next months World Health Assembly, just as it is possible for China to open its doors to further investigations into the origins of Covid-19, or for the US government to face down the pharmaceutical giants keeping a firm grip on intellectual property rights.
The realist in me says we are likely to emerge with few meaningful protections. As Horton noted a year ago: Delivering a global agreement on pandemic preparedness and response would be challenging even in the best of circumstances. And todays fractured and hostile world does not present the best of circumstances.
Failure to secure an agreement would be a tragedy for which we would pay a terrible price, perhaps dangerously soon.
David Dodwell is CEO of the trade policy and international relations consultancy Strategic Access, focused on developments and challenges facing the Asia-Pacific over the past four decades
This brief is part of a larger research project, Cities as Home, carried out by IOM Iraq, the Returns Working Group, and Social Inquiry, that explores both drivers and deterrents of integration across 14 urban locations that still host the largest share of IDPs in the country. The outputs of this project also include an analysis report on determinants of integration for IDPs and host community members, factsheets for each location, and four detailed case studies.
Milton, along with fellow experts from around the globe, drafted a consultation report outlining types of respiratory virus transmission and airborne infections the main focus of Milton's work for the past 25 years. The report sought to establish wording that could be easily used and understood by all professional groups.
The report corrects a number of misconceptions and misunderstandings that were major problems earlier in the COVID-19 pandemic. said Milton. It is important to have clear terminology and a shared understanding as a basis for developing effective policy to prevent infection and control pandemics.
The report proposes airborne transmission/inhalation as the best term for infectious respiratory particles emitted into the air and breathed in. This transmission can cause infection and can occur when the particles travel both short and long distances from the person with the infection.
When infectious respiratory particles follow a semi-ballistic trajectory over a short distance through the air and land directly onto the mouth, nose or eyes of another individual, the report proposes using the term direct deposition.
The report states clearly that the risk of airborne/inhalation transmission is greatest close to an infected person, Milton said.
The new report offers clarification that infectious particles floating in the air can be various sizes. Because the terms aerosol and droplet were misunderstood or used differently in different scientific disciplines, these terms were avoided in this report.
Though the report helps clarify terminology for important modes of respiratory infection transmission, Milton notes that there is still a great deal of work needed to reach scientific consensus on the relative importance of each mode for specific infectious agents.
These two modes are very different. They require very different controls to protect healthcare workers and other high-risk people, Milton said. How this report is translated into infection prevention and control policy will be critical that work lies ahead. Acknowledging that airborne/inhalation and direct deposition transmission are very different, as described in the body of the report, could be a first step toward new and more effective policies.
This report, 20 years after the release of pivotal research in the New England Journal of Medicine outlining the airborne transmission of SARS-CoV-1 and Miltons NEJM Perspective on airborne transmission, is one step WHO is taking to standardize scientific terminology. The organization plans to research this topic further through the collaboration of scientists in other disciplines and explore broader implications the updated terminology may have on health care.
I hope that this report will help move that process toward a stronger foundation in the science of airborne infection, Milton said.
-By Sumaya Abdel-Motagaly 26
Thinking about getting a spring-time booster shot?A new studycoming out of York University's Centre for Disease Modelling in the Faculty of Science shows that immunity after a COVID-19 booster lasts much longer than the primary series alone. These findings are among other, sometimes "unintuitive," revelations of how factors like age, sex and comorbidities do and don't affect immune response.
The study's authorsYork Post Doctoral researchers Chapin Korosec and David Dick, Applied Mathematics Professor Iain Moyles and Professor James Watmough with the University of New Brunswickused health data submitted to the Covid Immunity Task-Force project for more than 150 individuals who received either Pfizer-BioNTechor Moderna COVID-19 vaccines to look at how immunity holds up over time.
Our approach as mathematicians is to create mathematical models of the immune system, and then calibrate those models to health care data in order to advance our understanding of the human immune system. It was really interesting to see the SARS-CoV-2 booster dose have such a huge increase in protective longevity capacity as compared to the primary series of two doses."
Chapin Korosec, study's lead author
Published today in the journalScientific Reports, the study used Canadian vaccine data collected from individuals living in long-term care, as well as frontline health-care workers working in long-term care and hospitals.
Looking at the group as a whole, the median length for the antibody half-life immune response was 63 days for the primary series, and increased to 115 days for those who went on to receive their boosters, a statistically significant finding, says Korosec.
It is well-established that age can affect how adept the body is at priming an immune response after vaccines, so much so that advanced age is considered a comorbidity itself, says Korosec.
"Chronological age is your time since birth. But you also have an immunological age, which is correlated to your chronological age, and is related to how your body loses its ability to prime against invading pathogens and produce antibodies as time marches on," explains Korosec. "What's convoluted is that as we age chronologically, the probability that we accrue diseases that can affect the immune system in unintuitive ways also increases."
Looking into this aspect, the researchers found that older adults did have a less long-lasting immune response, but once they controlled for other comorbidities such as hypertension, lung disease and cancer, age no longer had as significant of an influence on the immune response.
Other interesting findings include a small, but statistically significant immune response for males versus females, and people with asthma having a longer lasting immune response more durable, in fact, than those with hybrid immunity from vaccines and contracting COVID-19.
"We found that some outcomes were surprising and worth further study, but of course we're not advocating any particular comorbidity is beneficial," says Dick. "We don't have any information from this study on how asthma would affect the severity of the COVID-19 illness, for example."
Outside of the strict findings, the researchers also say the study points to the importance of interdisciplinary research and are excited about the possibilities for collaboration, with plans to open York's medical school in 2028.
"While we're all from math and stats departments, the data comes from clinicians who went through medical school and are now professors studying immunology, and I think this study shows how people with different skill sets can come together and do really interesting science," says Korosec.
Adds Moyles: "We have a really top applied math program at York, and now the university has announced a medical school. Imagine these clinicians were at York and we had access to the data on the ground floor. This would cut the research timeline by years and has huge potential for future interdisciplinary research at the university."
Source:
Journal reference:
Korosec, C. S., et al. (2024). SARS-CoV-2 booster vaccine dose significantly extends humoral immune response half-life beyond the primary series.Scientific Reports. doi.org/10.1038/s41598-024-58811-3
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The North Carolina Court of Appeals ruled Tuesday that Gov. Roy Coopers closure of certain bars, but not restaurants, in the early months of the pandemic was irrational and arbitrary, not based on data and science.
Our careful review of the Record does not reveal the existence of any scientific evidence demonstrating Plaintiffs bars, as opposed to the bars located in other establishments serving alcohol, posed a heightened risk at the time Executive Order No. 141 was issued, wrote Judge April C. Wood, a Republican. Overall, the articles and data submitted by Defendant entirely fail to address any differences in the risk of spread of COVID-19 between the bars he allowed to reopen and Plaintiffs bars which remained closed.
Cooper issued an executive order early in the pandemic, on March 17, 2020, closing all bars in North Carolina. On May 20, 2020, he issued another executive order, allowing some but not all bars to reopen with specific safety precautions. Coopers attorneys said hed relied on science and data to determine which types of bars should be allowed to open and which should remain closed, using research showing that bars presented a higher risk of COVID-19 transmission.
But Woods 39-page opinion, joined by Republican colleagues Judges Donna Stroud and Jefferson Griffin, who is also running for the state Supreme Court, said that Cooper did not submit any evidence that showed why members of the North Carolina Bar and Tavern Association the plaintiff in the lawsuit would have been unable to comply with his executive order, when he allowed other types of bars to reopen under certain restrictions.
It is illogical and arbitrary to attempt to achieve Defendants stated health outcomes by applying different reopening standards to similarly situated businesses that could have complied with those standards, Wood wrote. In other words, if restaurants serving alcohol could operate at fifty percent capacity and keep groups six feet apart with both food and alcohol at the customers tables, Defendant has failed to present any forecast of evidence of any reason bars would not be able to do the same with alcohol service.
Cooper wrote in the executive order that bars presented a greater risk to spreading COVID-19, due to factors such as people traditionally interacting in that space in a way that would spread COVID-19 . . . or a business model that involves customers or attendees remaining in a confined indoor space over a sustained period.
But Wood wrotein her ruling that Cooper didnt have sufficient science and data at the time of the executive order to justify closing some bars and not others.
Most of the information is news articles, at best anecdotal reports of various incidents in different places around the world, Wood wrote. None of the information addresses any differences in risk of COVID-19 transmission between Plaintiffs bars and the other types of bars allowed to reopen.
Wood wrote that news reports cited by Coopers attorneys were not the same as scientific studies.
Research such as these news articles could be conducted by private citizens utilizing Internet search engines, Wood wrote. In fact, many of the documents in the Record were gathered from Internet searches as evidenced by the tags and links at the bottom of the printed pages.
The panel sent the case back down to the trial court for further proceedings.
Wood and her colleagues did not agree with every argument the Bar and Tavern Association made. The court ruled that the associations members were not entitled to financial compensation under the Emergency Management Act because Cooper did not physically take their land or property; he merely prohibited them from using their land for the purpose of conducting their business. Wood wrote that what Cooper did was within the bounds of state law, and not within the parts of the statute the legislature determined would give someone a right to compensation.
Clearly, the General Assembly considered which governmental actions would trigger a statutory right to compensation and employed language which encompassed certain specific actions while excluding others, wrote Judge April C. Wood, a Republican. Ordering mandatory business closures is not one of those actions which triggers a statutory right of compensation under the statute as it is currently written.
Click here to read the courts ruling in N.C. Bar and Tavern Association v. Cooper.
