Tag: 1/11/24

Categories : Paediatrics VaccinesTags : Leave a comment

Maternal Antibodies in Infants Interfere with Malaria Vaccine Responses

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Photo by Mufid Majnun on Unsplash

Maternal antibodies passed across the placenta can interfere with the response to the malaria vaccine, which would explain its lower efficacy in infants under five months of age, according to research led by the Barcelona Institute for Global Health (ISGlobal), in collaboration with seven African centers (CISM-Mozambique, IHI-Tanzania, CRUN-Burkina Faso, KHRC-Ghana, NNIMR-Ghana, CERMEL-Gabon, KEMRI-Kenya).

The findings, published in Lancet Infectious Diseases, suggest that children younger than currently recommended by the WHO may benefit from the RTS,S and R21 malaria vaccines if they live in areas with low malaria transmission, where mothers have less antibodies to the parasite.

The world has reached an incredible milestone: the deployment of the first two malaria vaccines –RTS,S/AS01E and the more recent R21/Matrix-M– to protect African children against malaria caused by Plasmodium falciparum. Both vaccines target a portion of the parasite protein called circumsporozoite (CSP) and are recommended for children aged 5 months or more at the moment of the first dose.

“We know that the RTS,S/AS01E malaria vaccine is less effective in infants under five months of age, but the reason for this difference is still debated,” says Carlota Dobaño, who leads the Malaria Immunology group at ISGlobal, a centre supported by “la Caixa” Foundation. 

To investigate this, Dobaño and her team analysed blood samples from more than 600 children (age 5-17 months) and infants (age 6-12 weeks) who participated in the phase 3 clinical trial of RTS,S/AS01E. Using protein microarrays, they measured antibodies against 1000 P. falciparum antigens before vaccination to determine if and how malaria exposure and age affected IgG antibody responses to the malaria vaccine.

“This microarray approach allowed us to accurately measure malaria exposure at the individual level, including maternal exposure for infants and past infections for older children,” says Didac Maciá, ISGlobal researcher and first author of the study. 

The role of maternal antibodies

The analysis of antibodies to P. falciparum in children who had received a control vaccine instead of RTS,S/AS01E revealed a typical “exposure” signature, with high levels in the first three months of life due to the passive transfer of maternal antibodies through the placenta, a decline during the first year of life, and then a gradual increase as a result of naturally acquired infections.

In children vaccinated with RTS,S/AS01E, antibodies induced by natural infections did not affect the vaccine response. However, in infants, high levels of antibodies to P. falciparum, presumably passed from their mothers during pregnancy, correlated with reduced vaccine responses. This effect was particularly strong for maternal anti-CSP antibodies targeting the central region of the protein. Conversely, infants with very low or undetectable maternal anti-CSP IgGs exhibited similar vaccine responses as those observed in children.

The molecular mechanisms underlying this interference by maternal antibodies are not fully understood, but the same phenomenon has been observed with other vaccines such as measles. 

Overall, these findings confirm something that was already suspected but not clearly demonstrated: despite their protective function, maternal anti-CSP antibodies, which decline within the first three to six months of life, may interfere with vaccine effectiveness. The higher the level of malaria transmission, the more maternal antibodies are transmitted to the baby, resulting in lower vaccine effectiveness. These findings further suggest that infants below five months of age may benefit from RTS,S or R21 vaccination in low malaria transmission settings, during outbreaks in malaria-free regions, or in populations migrating from low to high transmission settings.

“Our study highlights the need to consider timing and maternal malaria antibody levels to improve vaccine efficacy for the youngest and most vulnerable infants,” says Gemma Moncunill, ISGlobal researcher and co-senior author of the study, together with Dobaño.

Source: Barcelona Institute for Global Health (ISGlobal)

Categories : Ageing VaccinesTags : Leave a comment

New Research Shows that Recombinant Shingles Vaccine Protects Against Dementia

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Photo by JD Mason on Unsplash

New research published in Nature has shown that the recombinant shingles vaccine, as with the live version, might have a protective effect against dementia.

While evidence is emerging that the live herpes zoster (shingles) vaccine might protect against dementia, it has now been replaced by recombinant vaccines in many countries. But a lack of data meant that whether the recombinant vaccines conferred the same benefit was unknown. Fortunately, since there was a rapid switch from live to recombinant vaccines, there was an opportunity for a natural experiment to compare the risk of dementia between vaccine types.

The study demonstrated that the recombinant vaccine is associated with a significantly lower risk of dementia in the 6 years post-vaccination. Specifically, receiving the recombinant vaccine is associated with a 17% increase in diagnosis-free time, translating into 164 additional days lived without a diagnosis of dementia in those subsequently affected.

The recombinant shingles vaccine was also associated with lower risks of dementia than were two other vaccines commonly used in older people: influenza and tetanus–diphtheria–pertussis vaccines. The effect was robust across multiple secondary analyses, and was present in both men and women but was greater in women. These findings should stimulate studies investigating the mechanisms underpinning the protection and could facilitate the design of a large-scale randomised control trial to confirm the possible additional benefit of the recombinant shingles vaccine.

Categories : Neurodegenerative Diseases NeurologyTags : Leave a comment

Major Discovery for the Understanding of Parkinson’s Disease: New Neurotransmitter

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Neurotransmitters at a synapse. Credit: Scientific Animations CC4.0

The treatment of certain neurodegenerative diseases and the pages of neuroscience textbooks may soon be in need of major update. A research team has discovered that a molecule in the brain – ophthalmic acid – unexpectedly acts like a neurotransmitter similar to dopamine in regulating motor function, offering a new therapeutic target for Parkinson’s and other movement diseases.

As reported in the journal Brain, researchers observed that ophthalmic acid binds to and activates calcium-sensing receptors in the brain, reversing the movement impairments of Parkinson’s mouse models for more than 20 hours.

Parkinson’s disease (PD) symptoms, which include tremors, shaking and lack of movement, are caused by decreasing levels of dopamine in the brain as those neurons die. L-dopa, the front-line drug for treatment, acts by replacing the lost dopamine and has a duration of two to three hours. While initially successful, the effect of L-dopa fades over time, and its long-term use leads to dyskinesia – involuntary, erratic muscle movements in the patient’s face, arms, legs and torso.

“Our findings present a groundbreaking discovery that possibly opens a new door in neuroscience by challenging the more-than-60-year-old view that dopamine is the exclusive neurotransmitter in motor function control,” said co-corresponding author Amal Alachkar, School of Pharmacy & Pharmaceutical Sciences professor. “Remarkably, ophthalmic acid not only enabled movement, but also far surpassed L-dopa in sustaining positive effects. The identification of the ophthalmic acid-calcium-sensing receptor pathway, a previously unrecognised system, opens up promising new avenues for movement disorder research and therapeutic interventions, especially for Parkinson’s disease patients.”

Alachkar began her investigation into the complexities of motor function beyond the confines of dopamine more than two decades ago, when she observed robust motor activity in Parkinson’s mouse models without dopamine. In this study, the team conducted comprehensive metabolic examinations of hundreds of brain molecules to identify which are associated with motor activity in the absence of dopamine. After thorough behavioural, biochemical and pharmacological analyses, ophthalmic acid was confirmed as an alternative neurotransmitter.

“One of the critical hurdles in Parkinson’s treatment is the inability of neurotransmitters to cross the blood-brain barrier, which is why L-DOPA is administered to patients to be converted to dopamine in the brain,” Alachkar said. “We are now developing products that either release ophthalmic acid in the brain or enhance the brain’s ability to synthesise it as we continue to explore the full neurological function of this molecule.”

Source: University of California – Irvine

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British Sleep Society Urges Getting Rid of Daylight Savings Time

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The British Sleep Society has released a position statement in the Journal of Sleep Research advocating for the abolition of the twice-yearly clock changes in the UK and the restoration of permanent Standard Time (Greenwich Mean Time). This recommendation is based on scientific evidence highlighting the adverse effects of the clock change and Daylight Saving Time (DST) on sleep and circadian health.

The British Sleep Society emphasises that sleep is central to health and well-being and the enforced changes of clock time to DST can interfere negatively with sleep regulation. “What we often don’t realise is that DST changes our schedules, moving them forward by one hour while daylight remains the same. DST forces us all to get up and go to work or school one hour earlier, often in the dark,” said co-author Eva Winnebeck, PhD, of the University of Surrey. The Society stresses that natural daylight in the morning is crucial for maintaining an alignment of our body clocks with day and night, which is essential for optimal sleep and overall health.

“Some people even advocate switching to DST all year around. We think this is misguided, because it would leave us with dark mornings during the winter, and morning light is critically important for keeping our body clocks synchronized,” says coauthor Malcolm von Schantz, PhD, of Northumbria University.

Other sleep societies have also argued against year-round DST and advocate for the return to year-round Standard Time, but this position statement is the first published UK perspective. “The unique location and orientation of our UK landmass needs to be considered because permanent DST would over-disadvantage people west and north of London,” said first author Megan Crawford, PhD, of the University of Strathclyde.

Source: Wiley

Categories : Exercise PaediatricsTags : Leave a comment

Outdoor Play Helps Protect Toddlers against Later Childhood Obesity

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New research published in Acta Paediatrica suggests that children who engage in outdoor play during their preschool years have a lower risk of developing obesity later in childhood.

The study included children born in Japan during two weeks in January and July 2001. Of 53 575 children born, 42 812 had data on outdoor play habits at age 2.5 years. In a survey, parents were asked, “Where do your children usually play (excluding home residences and daycare centres attended)?” Available options for answers included “in my garden or on the grounds of my apartment complex,” “in parks,” “in natural areas such as fields, forests, and beaches,” “on the street,” “in shrines and temples,” “in playgrounds in department stores and supermarkets,” “other,” and “don’t play anywhere but inside my home.” If one or more of the first five items were chosen, a child was considered to have exposure to outdoor play—this was the case for 91% of the children.

In follow-up surveys when the children were seven years old, 31 743 of 42 812 (74%) children had height and weight data, with 10% classified as overweight or obese.

Compared with children without exposure to outdoor play, children with outdoor play habits had 15% lower odds of being overweight or obese, after adjusting for other influencing factors.

“We suggest that parents and caregivers encourage outdoor play habits in their children at an early age, as this may help prevent obesity later in life,” said corresponding author Takahiro Tsuge, MPH, of Kurashiki Medical Center.

Source: Wiley