Category: Vaccines

Flu Jab May Protect Against Developing Alzheimer’s

Old man
Source: JD Mason on Unsplash

In a study with nearly 2 million older adults, those who received at least one influenza vaccine were 40% less likely than their non-vaccinated peers to develop Alzheimer’s disease over four years of follow-up, according to a new study from UTHealth Houston.

An early online version of the paper detailing the findings is available in advance of its publication in the Journal of Alzheimer’s Disease in August.

“We found that flu vaccination in older adults reduces the risk of developing Alzheimer’s disease for several years. The strength of this protective effect increased with the number of years that a person received an annual flu vaccine – in other words, the rate of developing Alzheimer’s was lowest among those who consistently received the flu vaccine every year,” said first author Avram S. Bukhbinder, MD. “Future research should assess whether flu vaccination is also associated with the rate of symptom progression in patients who already have Alzheimer’s dementia.”

The study comes two years after UTHealth Houston researchers found a possible link between the flu vaccine and reduced risk of Alzheimer’s disease. This new study analysed a much larger sample than previous research, including 935 887 flu-vaccinated patients and 935 887 non-vaccinated patients.

During four-year follow-up appointments, about 5.1% of flu-vaccinated patients were found to have developed Alzheimer’s disease. Meanwhile, 8.5% of non-vaccinated patients had developed Alzheimer’s disease during follow-up.

These results underscore the strong protective effect of the flu vaccine against Alzheimer’s disease, according to Bukhbinder and Schulz. However, the underlying mechanisms behind this process require further study.

“Since there is evidence that several vaccines may protect from Alzheimer’s disease, we are thinking that it isn’t a specific effect of the flu vaccine,” said Professor Paul. E. Schulz, MD, senior author of the study. “Instead, we believe that the immune system is complex, and some alterations, such as pneumonia, may activate it in a way that makes Alzheimer’s disease worse. But other things that activate the immune system may do so in a different way – one that protects from Alzheimer’s disease. Clearly, we have more to learn about how the immune system worsens or improves outcomes in this disease.”

Past research has uncovered a decreased risk of dementia associated with prior exposure to various adulthood vaccinations, including those for tetanus, polio, and herpes, in addition to the flu vaccine and others.

Additionally, as more time passes since the introduction of the COVID vaccine and longer follow-up data becomes available, Dr Bukhbinder said it seeing if there is a similar link between COVID vaccination and the risk of Alzheimer’s disease.

Source: The University of Texas Health Science Center at Houston

Why The Malaria Vaccine Quickly Loses its Effectiveness

Image source: Ekamalev at Unsplash

More than 600 000 people worldwide still die from malaria every year, according to the WHO. The vast majority of fatal cases of malaria are caused by the single-celled pathogen Plasmodium falciparum, which so far has only one approved vaccine against it, and its efficacy, which is already rather low, is also short-lived. A new study in Science Immunology may have the explanation: a lack of cross-reactivity in T helper cells.

The vaccine targets CSP, the quantitatively dominant protein on the surface of the “sporozoites”. Sporozoites are the stage of the malaria pathogen which is transmitted with the bite of the mosquito and enters human blood. “To improve the vaccine, we need to understand which protective antibodies are induced by the immunisation. But the production of such antibodies depends to a large extent on help from the so-called follicular T helper cells,” explained Dr Hedda Wardemann, immunologist and senior author of the study. “They ensure that B cells transform into antibody-producing plasma cells and memory B cells.”

To study the T helper cell response against CSP in detail, Dr Wardemann’s team examined the blood of volunteers infected with killed P. falciparum sporozoites from the vaccine strain. The volunteers were of European descent and had no prior contact with malaria pathogens. The researchers analysed the induced Plasmodium-specific follicular T helper cells at the single cell level. They focused on which sequences of CSP are recognised by the T helper cells’ receptors.

The analyses revealed that the T-cell receptors mainly targeted amino acids 311 to 333 of the CSP. But the researchers were stunned by another finding: there was virtually no cross-reactivity between the individual T-cell clones. “The receptors highly specifically bind only the CSP epitopes of the vaccine strain used. Even deviations of only a single amino acid component were not tolerated in some cases,” Dr Wardemann explained.

The immunologist points out that in the natural population of P. falciparum, sequence polymorphisms occur to a high degree in this region of the CSP. “The specificity of the T-cell clones prevents the constantly recurring natural infections with the pathogen from acting as a natural ‘booster.’ This could possibly explain why the protective effect of the malaria vaccine wears off so quickly,” Dr Wardemann said. The researcher recommends that further development of the vaccine should test whether inducing a broader spectrum of T helper cells could generate longer-lasting immune protection.

Source: German Cancer Research Centre

A Crystal Clear Look at Rabies Opens up New Vaccines

Scientists from La Jolla Institute for Immunology and the Institut Pasteur have shed light on the structure of the rabies virus glycoprotein, seen here. Credit: Heather Callaway, Ph.D., LJI

In a new study, researchers from La Jolla Institute have unveiled one of the first high-resolution looks at the rabies virus glycoprotein in its vulnerable ‘trimeric’ form. These new images, published in Science Advances, may open up a new vaccine for the deadly virus.

The CDC estimates that 59 000 people die from rabies virus every year, with 40% of those bitten by rabid animals being under 15. Some victims, especially kids, don’t realise they’ve been exposed until it is too late. The intense rabies treatment regimen is not widely available and the average $3800 is out of the reach of less well-off families.

Rabies vaccines, rather than treatments, are much more affordable and easier to administer. But according to Professor Erica Ollmann Saphire, PhD, of the La Jolla Institute, lead researcher of the new study, those vaccines also come with a massive downside.

“Rabies vaccines don’t provide lifelong protection. You have to get your pets boosted every year to three years,” she said. “Right now, rabies vaccines for humans and domestic animals are made from killed virus. But this inactivation process can cause the molecules to become misshapen – so these vaccines aren’t showing the right form to the immune system. If we made a better shaped, better structured vaccine, would immunity last longer?”

“The rabies glycoprotein is the only protein that rabies expresses on its surface, which means it is going to be the major target of neutralising antibodies during an infection,” said LJI Postdoctoral Fellow Heather Callaway, PhD, the study’s first author.

“Rabies is the most lethal virus we know. It is so much a part of our history – we’ve lived with its spectre for hundreds of years,” added Prof Saphire. “Yet scientists have never observed the organisation of its surface molecule. It is important to understand that structure to make more effective vaccines and treatments – and to understand how rabies and other viruses like it enter cells.”

Shapeshifting Rabies virus evades antibodies

Why rabies vaccines don’t provide long-term protection is still unclear, but they do know that its shape-shifting proteins are a problem.

The rabies glycoprotein has sequences that unfold and flip upward when needed, like a Swiss Army knife. The glycoprotein can shift back and forth between pre-fusion (before fusing with a host cell) and post-fusion forms. It can also come apart, changing from a trimer structure (where three copies come together in a bundle) to a monomer (one copy by itself).

This shapeshifting can make rabies invisible to human antibodies, which are built to recognise a single site on a protein. They cannot follow along when a protein transforms to hide or move those sites.

The new study gives scientists a critical picture of the correct glycoprotein form to target for antibody protection.

Capturing the glycoprotein at last

Over the course of three years, Callaway worked to stabilise and freeze the rabies glycoprotein in its pre-fusion form.

Callaway paired the glycoprotein with a human antibody, which helped her pinpoint one site where the viral structure is vulnerable to antibody attacks. The researchers then captured a 3D image of the glycoprotein using cutting-edge cryo-electron microscope equipment at LJI. 

The new 3D structure highlights several key features researchers hadn’t seen before. Importantly, the structure shows the fusion peptides, the way they appear in real life. These two important sequences link the bottom of the glycoprotein to the viral membrane, but project into the target cell during infection. Getting stable image of these sequences is challenging: other rabies researchers have had to cut them off to try to get images of the glycoprotein.

Dr Callaway solved this problem by capturing the rabies glycoprotein in detergent molecules. “That let us see how the fusion sequences are attached before they snap upward during infection,” said Prof Saphire.

Now that scientists have a clear view of this viral structure, they can better design vaccines to create antibodies with a better picture of the targt.

“Instead of being exposed to four-plus different protein shapes, your immune system should really just see one – the right one,” said Dr Callaway. “This could lead to a better vaccine.”

Preventing a family of viruses

More images are needed of rabies virus and its relatives together with neutralising antibodies, and could reveal common antibody targets for lyssaviruses, which can also infect humans and animals. According to Dr Callaway, scientists are working on solving several of these structures, which could reveal antibody targets that lyssaviruses have in common.

“Because we didn’t have these structures of the rabies virus in this conformational state before, it’s been hard to design a broad-spectrum vaccine,” Dr Callaway said.

Source: La Jolla Institute for Immunology

New Vaccines Could Focus on T Cell Response – Without Antibodies

T cell
Scanning Electron Micrograph image of a human T cell. Credit: NIH/NIAID

In a groundbreaking new study, scientists report training T cells to protect against SARS-CoV-2 even without an antibody response. This could open the way to more broadly effective vaccines.

The study’s findings appear in the Proceedings of the National Academy of Sciences.

Current vaccines prompt the creation of antibodies and immune cells that recognise the spike protein. However, these vaccines were developed using the spike protein from an older variant of SARS-CoV-2, reducing their effectiveness against newer variants. Researchers have found that immune cells called T cells tend to recognise parts of SARS-CoV-2 that don’t mutate rapidly. T cells coordinate the immune system’s response and kill cells that have been infected by the SARS-CoV-2 virus.

A vaccine that prompted the body to create more T cells against SARS-CoV-2 could help prevent disease caused by a wide range of variants. To explore this approach, a research team led by Dr Marulasiddappa Suresh from the University of Wisconsin studied two experimental vaccines that included compounds to specifically provoke a strong T-cell response in mice.

The team tested the vaccines’ ability to control infection and prevent severe disease caused by an earlier strain of SARS-CoV-2 as well as by the Beta variant, which is relatively resistant to antibodies raised against earlier strains.

When the researchers vaccinated the mice either either nasally or by injection, the animals developed T cells that could recognise the early SARS-CoV-2 strain and the Beta variant. The vaccines also caused the mice to develop antibodies that could neutralise the early strain. However, they failed to create antibodies that neutralised the Beta variant.

The mice were exposed to SARS-CoV-2 around 3 to 5 months after vaccination. Compared to the controls, vaccinated mice had very low levels of virus in their lungs and were protected against severe illness, which was true of infection with the Beta variant too. This showed that the vaccine provided protection against the Beta variant despite failing to produce effective antibodies against it.

To understand which T cells were providing this protection, the researchers selectively removed different types of T cells in vaccinated mice prior to infection. When they removed CD8 (killer) T cells, vaccinated mice remained well protected against the early strain, although not against the Beta variant. When they blocked CD4 T (helper) cells, levels of both the early strain and Beta variant in the lungs and severity of disease were substantially higher than in vaccinated mice that didn’t have their T cells removed.

These results suggest important roles for CD8 and CD4 T cells in controlling SARS-CoV-2 infection. Current mRNA vaccines do produce some T cells that recognize multiple variants. This may help account for part of the observed protection against severe disease from the Omicron variant. Future vaccines might be designed to specifically enhance this T cell response.

“I see the next generation of vaccines being able to provide immunity to current and future COVID variants by stimulating both broadly-neutralising antibodies and T cell immunity,” Dr Suresh predicted.

Source: National Institutes of Health

Did a Flu Vaccine Reduce Severe COVID Risk by 89%?

Vaccine injection
Image source: NCI on Unsplash

In a study of more than 30 000 health-care workers in Qatar, those who got a flu jab were 89% less likely to develop severe COVID over the next few months.

The study, which is published in Nature, was conducted in late 2020, before COVID vaccines were rolled out. Its findings align with previous work suggesting that ramping up the immune system using influenza vaccines and other jabs could help the body to fend off the coronavirus SARS-CoV-2.

In the early months of the pandemic, there was great interest as to whether existing vaccines could confer some protection against SARS-CoV-2. But collecting strong evidence for such an effect is difficult, because people who sought out vaccination for other diseases could also make lifestyle choices that reduce the odds of catching COVID.

To reduce this ‘healthy-user effect’, a team led by Laith Jamal Abu-Raddad, an infectious-disease epidemiologist at Weill Cornell Medicine–Qatar in Doha, analysed the health records of 30 774 medical workers in the country. There is probably less variation in health-related behaviour among such workers than in the general population, reducing (but not eliminating) bias, Abu-Raddad said.

The researchers tracked 518 workers who tested positive for SARS-CoV-2 and matched them to more than 2000 study participants who had tested negative for the virus. Those who had received an influenza vaccine that season were 30% less likely to test positive for SARS-CoV-2, and 89% less likely to develop severe COVID, compared with workers who had not (although the number of severe cases was small in both groups). The study was posted on the medRxiv preprint server on 10 May.

Günther Fink, an epidemiologist at the University of Basel in Switzerland, said that the Qatar analysis makes it less likely that other studies reporting the same link were a fluke. His team reported that flu vaccines were associated with lower mortality in hospitalised COVID patients in Brazil.

“This is an important piece of evidence,” says Mihai Netea, an infectious-disease specialist at Radboud University Medical Center in Nijmegen, the Netherlands. The observation that influenza vaccines are linked to a reduction in not just SARS-CoV-2 infections, but also disease severity, strongly suggests that the protection is genuine, he adds.

How long this protection lasts is unclear. Among those in the Qatar study who had the flu jab and later contracted COVID, Abu-Raddad’s team recorded SARS-CoV-2 infections occurring, on average, about six weeks after vaccination. “I don’t expect to see this effect lasting long at all,” he says. Netea guesses that the benefits last for between six months and two years.

Exactly why flu vaccines, which are inactivated viruses, would also protect against COVID is unclear. Vaccines teach the immune system about specific pathogens, but they also stimulate broad-acting antiviral defences, said Netea, who has found signs of such responses in flu-vaccine recipients.

Netea’s team is also working to better quantify the benefits of vaccines targeting influenza and other diseases against COVID. His team has launched a randomised, placebo-controlled trial in Brazil that will test whether influenza and measles–mumps–rubella vaccines can protect against COVID, fully excluding the healthy-user effect.

Knowing that vaccines for flu and other diseases can offer protection against COVID, even if only partial and for a limited period, could limit the damage caused by a future pandemic before a vaccine for that disease is developed, Netea argues. “If you have something in the beginning, you could save millions of lives.”

Source: Nature

Rollout of World’s First Malaria Vaccine in Sub-Saharan Africa

Mosquito, a malaria parasite vector
Photo by Егор Камелев on Unsplash

The world’s first malaria vaccine will soon be available across sub-Saharan Africa, according to PATH, partners of the vaccine developers, as positive results from the pioneering jab pile up.

The vaccine, known as RTS,S/AS01E and commercialised under the brand name Mosquirix, targets children as over three quarters of malaria deaths occur in under-five-year olds, according to the latest report from the WHO.

Findings from a WHO pilot held in Ghana, Kenya and Malawi, showed that the pioneering vaccine caused a significant reduction in severe malaria and hospitalisation among vaccinated children.

It means more countries in sub-Saharan Africa will soon receive the vaccine, says John Bawa, Africa lead for vaccine implementation at Program for Appropriate Technology in Health (PATH).

These findings pave the way for an expanded distribution scheme that will see countries like Mozambique, Nigeria and Zambia receive the vaccines, said Bawa during a webinar held in commemoration of World Malaria Day.

“The next is to deploy the vaccine to other endemic countries. Countries that are interested in the vaccine are expected to apply to GAVI from June to September,” he said at the webinar organised by the African Media and Malaria Research Network (AMMREN), PATH and Kintampo Health Research Centre (KHRC).

“Countries like Mozambique, Uganda, Zambia and Nigeria have already written officially to express interest for the vaccine,” Bawa said.

He said malaria vaccine coverage in Malawi was at 88% in 2020 and 93% in 2021. In Ghana, it was 71% in 2020 and 76% in 2021 and in Kenya, it was 69% in 2020 and 83% in 2021.

“These numbers indicate strong community demand and capacity of childhood vaccination platforms to effectively deliver the vaccine to children,” said Bawa.

Currently, 1 million children in Ghana, Kenya and Malawi have received at least one dose of the first malaria vaccine.

These vaccines were distributed in a pilot scheme organized by WHO. The organisation has now recommended the vaccine for use among children in areas with moderate to high transmission rate of malaria.

“This vaccine is not just a scientific breakthrough, it is life-changing for families across Africa. It demonstrates the power of science and innovation for health,” WHO Director-General Dr Tedros Adhanom Ghebreyesus said.

Vaccine procurement

In an arrangement to boost vaccine supply and coverage, GlaxoSmithKline, producers of the RTS,S vaccine, will transfer technology and patent to Bharat Biotech in India to manufacture the vaccines.

The WHO, in a press release, said more than US$155 million has been secured from to support the introduction, procurement and delivery of the malaria vaccine for Gavi-eligible countries in sub-Saharan Africa.

The organisation said it would provide guidance for countries that are considering the use of vaccines for the reduction childhood illnesses and deaths from malaria.

“For some countries, Gavi is paying about 80% [of the] cost of the vaccine, while it is expected that the country’s government would pay the [remaining] 20%,” Bawa said.

Wellington Oyibo, director of the Centre for Malaria Diagnosis, Research, Capacity Building and Policy at the University of Lagos, urged African leaders to ensure that their counterpart funds are available to purchase the vaccine.

He said the Nigerian government and the Prince Ned Nwoko Foundation malaria eradication project have applied to purchase the vaccine for Nigerian children.

Oyibo said while the initial rollout of the vaccine may not go around the country, the Nigerian government selected states with the highest malaria burden to begin with.

Reproduced under a Creative Commons Attribution License.

Source: SciDev.Net

BCG Vaccine Activates Immune System in Newborns

Source: Raghavendra V Konkathi on Unsplash

In the century since it was first used in humans, the Bacille Calmette-Guérin (BCG) vaccine against tuberculosis has become one of the world’s most widely used vaccines. Administered in countries with endemic TB, it has surprisingly been found to protect newborns and young infants against multiple bacterial and viral infections unrelated to TB. Some evidence even suggests that it can reduce severity of COVID. Now, a new study in Cell Reports sheds light on the mechanisms behind its extra protective effects.

Surprisingly little is known about how BCG exerts its many side benefits. To better understand its mechanism of action, researchers collected and comprehensively profile blood samples from newborns vaccinated with BCG, using a powerful ‘big data’ approach analysing lipid and metabolite biomarkers.

Their study found that the BCG vaccine induces specific changes in metabolites and lipids that correlate with innate immune system responses. The findings provide clues toward making other vaccines more effective in vulnerable populations with distinct immune systems, such as newborns.

First author Dr Joann Diray Arce and her colleagues started off with blood samples from low-birthweight newborns in Guinea Bissau who were enrolled in a randomised clinical trial to receive BCG either at birth or after a delay of six weeks. Blood samples were taken at four weeks for both groups (after BCG was given to the first group, and before it was given to the second group).

The researchers comprehensively profiled the impact of BCG immunisation on the newborns’ blood plasma. They found that BCG vaccines given at birth changed metabolite and lipid profiles in newborns’ blood plasma in a pattern distinct from those in the delayed-vaccine group. The changes were associated with changes in cytokine production, a key feature of innate immunity.

The researchers had parallel findings when they tested BCG in cord blood samples from a cohort of Boston newborns and samples from a separate study of newborns in The Gambia and Papua New Guinea.

“We now have some lipid and metabolic biomarkers of vaccine protection that we can test and manipulate in mouse models,” said Dr Arce. “We studied three different BCG formulations and showed that they converge on similar pathways of interest. Reshaping of the metabolome by BCG may contribute to the molecular mechanisms of a newborn’s immune response.”

“A growing number of studies show that BCG vaccine protects against unrelated infections,” said Ofer Levy, MD, PhD, the study’s senior investigator. “It’s critical that we learn from BCG to better understand how to protect newborns. BCG is an ‘old school’ vaccine – it’s made from a live, weakened germ – but live vaccines like BCG seem to activate the immune system in a very different way in early life, providing broad protection against a range of bacterial and viral infections. There’s much work ahead to better understand that and use that information to build better vaccines for infants.”

Source: Boston Children’s Hospital via News-Medical.Net

In Flu Season, Vaccine Reduces Cardiovascular Events in Heart Failure

Woman sneezing
Photo by Andrea Piacquadio on Unsplash

A randomised controlled trial showed that people with heart failure receiving an annual flu shot had lower rates of pneumonia and hospitalisation on a year-round basis and a reduction in major cardiovascular events during peak flu season – but not year-round.

The study, presented at the American College of Cardiology’s 71st Annual Scientific Session, is the first randomised controlled trial to assess the benefits of the flu vaccine in people with heart failure, who face a high risk of cardiovascular events. It was conducted in countries across Asia, Africa and the Middle East where getting a flu shot is not commonplace.

Lead author Mark Loeb, MD, said: “Although our prespecified endpoints were not significant, our data suggest that there’s a clinical benefit [to getting a flu shot] given the clear reduction in pneumonia, moderate reduction in hospitalisation and reduction in vascular events and deaths during periods of peak influenza. When taken together with previous trials and observational studies, the collective data demonstrate there is a substantial benefit to receiving a flu vaccine for people with heart failure.”

Heart failure is a condition in which the heart becomes too weak or stiff to pump blood effectively. Previous studies have shown that people with heart disease or cardiovascular risk factors face an elevated risk of complications when they contract influenza, but there has been a lack of evidence on whether flu vaccines can help to mitigate this risk specifically in people with heart failure.

The trial enrolled 5129 patients with heart failure in 10 countries where flu vaccines are not common. Participants did not routinely get flu shots and had previously received a flu shot no more than once during the three years preceding the trial. Participants were randomised to receive a flu shot or a placebo annually for up to three years, though they could still get a flu shot outside of the trial. Researchers tracked health outcomes for a median of 2.9 years. The trial’s primary endpoint was a composite of death from cardiovascular causes, non-fatal heart attack or non-fatal stroke. Its co-primary endpoint included a composite of any of these events plus hospitalisation for heart failure.

Overall, the composite primary endpoint occurred in 691 participants and 1470 experienced the composite co-primary endpoint. When analysed on a year-round basis there was no significant difference in the rates of these events between those who had received a flu vaccine and those who had not.

Separate analyses of hospitalisation, pneumonia and other respiratory outcomes however found that rates of pneumonia were 42% lower and hospitalisations were down 15% among those who received a flu shot.

The flu vaccine arm showed a significant reduction in the first primary endpoint, as well as reductions in all-cause death and cardiovascular death, when the analysis was limited to periods of peak influenza circulation. When influenza circulation was low, no significant difference was seen.

The researchers accounted for the differences in influenza circulation seasons. Based on these results, researchers said the flu vaccine did help to protect patients from influenza complications, including cardiovascular events.

“Many of the effects we found during peak flu circulation disappeared outside of it,” Dr Loeb said. “There’s no biological explanation for that other than influenza infections.”

While the study was conducted in countries where the flu vaccine is either not widely available or not common to receive, Dr Loeb said the results could likely be generalisable even in countries where flu vaccine uptake is higher. Study participants were allowed to get a flu vaccine outside of the study, but Dr Loeb said that there was no impact on the findings as very few did so. He added that the study was stopped early in four countries due to the COVID pandemic.

Loeb said that additional trials and large-scale observational studies could further clarify the health benefits of influenza vaccination in people with cardiovascular disease.

“I think this study offers an important message about vaccines generally – that it is important to do randomised controlled trials in populations that historically haven’t had a very high uptake of vaccines,” Dr Loeb said. “These types of [research] gaps have to be filled.”

Source: American College of Cardiology

Intranasal Flu Vaccine OK for Kids with Asthma

Young girl sneezing
Photo by Andrea Piacquadio on Unsplash

A small clinical trial published in Pediatrics has shown that intranasal flu vaccine is just as safe for children with asthma as the intramuscular vaccine. According to the researchers, within 42 days of vaccination, 10.8% of children who received the intranasal quadrivalent live attenuated influenza vaccine (LAIV4) had an asthma exacerbation compared with 14.7% of those who received the intramuscular quadrivalent inactivated influenza vaccine (IIV4).

According to the researchers, regardless of asthma severity, LAIV4 remained noninferior to IIV4. Among those with mild asthma, one of 25 kids who received the LAIV4 experienced an asthma exacerbation versus three of 16 in the IIV4 group, the researchers reported. In children with moderate to severe asthma, exacerbations occurred in seven of 49 in the LAIV4 group and seven of 52 in the IIV4 group.

“These data add to the compelling safety record of LAIV in children, including those with persistent asthma,” the researchers wrote.

The two groups also did not differ significantly in the frequency of asthma-related symptoms, including nighttime awakening, unscheduled albuterol use, cough, wheezing, or chest tightness, within 14 days of administration. Similarly, no differences were seen in peak expiratory flow rate, or changes in childhood asthma control test or asthma control test scores from baseline through 42 days.

At present, the CDC recommends against the nasal spray vaccine for children and people with asthma, citing an increased risk of exacerbations.

A previous study had suggested that the LAIV was linked increased asthma risk and reactive airway disease in children under 36 months of age, but more recent research has found no difference in risk between the LAIV and IIV, the researchers explained.

“Building off these previous studies, our prospective study suggests that LAIV may be appropriate for some children with asthma,” they noted.

“These data support reexamining precautions to using LAIV4 in children with asthma, which could be particularly important during influenza pandemics, at times when IIV4 supplies are limited, in situations of public/school mass vaccination clinics using LAIV, or for children with significant needle aversions,” they added.

The study was conducted over the 2018 and 2019 flu seasons with children aged five to 11 but expanded to include children ages 5 to 17 in its second year. The primary outcome of asthma exacerbation after 42 days was defined as an episode for which the participant sought medical care or a new prescription for corticosteroids.

The median age of the 151 enrolled participants was 9 years, and 58% were boys.

Systemic reactogenicity events in the 14 days after vaccination were not different between the LAIV4 and IIV4 groups, with the exceptions of myalgia and sore throat, which were more common in the IIV4 group.

Source: MedPage Today

Boosting the BCG Vaccine by Blocking IL-10

Vaccine injection
Image source: NCI on Unsplash

Briefly blocking interleukin-10 (IL-10) when administering the BCG vaccine for tuberculosis vastly improves long-term protection in mice, researchers reported in the Journal of Immunology. The finding, if it continues to hold true in nonhuman primates and clinical trials, has the potential to save millions of lives.

“We are very excited that we can reverse BCG’s waning effectiveness by combining it with a host-directed therapy into one dose, which makes it very practical for the clinic,” said senior author Joanne Turner, PhD.

The study builds on research showing the effect of IL-10 on TB, which normally helps dampen excessive inflammation during infection, but Dr Turner’s previous work showed that IL-10 overall actually drives infection.

The researchers combined the BCG vaccine with an antibody that blocks IL-10 activity for about one week. Since the antibody targets the host, not the pathogen, that makes it a “host-directed therapy.” They gave the mixture to mice in one shot, waited six weeks to ensure the IL-10 blocker was no longer present and the BCG protection had been generated, and then exposed the mice to TB. Those mice controlled TB infection for nearly a year, which is significant for mice with normal lifespans of about two years. In contrast, mice given only the BCG vaccine lost control of TB infection within two months and had significant inflammation and damage in the lungs. Notably, the mice given the vaccine/IL-10 blocker had higher levels of various long-term memory immune cells, which are critical for ongoing TB control.

“This shows that the early development of an immune response is key for controlling TB infection in the long run, and that IL-10 inhibits the development of that long-term immunity,” Dr Turner said. “But by briefly blocking IL-10 at the same time as giving the vaccine, it allows the vaccine and immune system to do their jobs, creating those long-lasting memory immune cells.”

The researchers plan to move to nonhuman primates and then human clinical trials if those are successful. The team is optimistic, especially since the BCG vaccine is already in widespread use and the IL-10 blocker is being tested against other diseases.

Source: Texas Biomedical Research Institute