Immune response to vaccine adjuvants during the first year of life

SummaryThe contribution of microglia in neurological disorders is emerging as a leading driver rather than a consequence of pathology. RNAseT2-deficient leukoencephalopathy is a severe childhood white matter disorder affecting patients in their first year of life and mimics a cytomegalovirus brain infection. The early onset and resemblance of the symptoms to an immune response suggest an inflammatory and embryonic origin of the pathology. In this study, we identify deficient microglia as an early marker of pathology. Using the ex utero development and the optical transparency of an rnaset2-deficient zebrafish model, we found that dysfunctional microglia fail to clear apoptotic neurons during brain development. This was associated with increased number of apoptotic cells and behavioural defects lasting into adulthood. This zebrafish model recapitulates all aspect of the human disease to be used as a robust preclinical model. Using microglia-specific depletion and rescue experiments, we identified microglia as potential drivers of the pathology and highlight tissue-specific approaches as future therapeutic avenues.

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Higher exhaled nitric oxide at 6 weeks of age is associated with less bronchiolitis and wheeze in the first 12 months of age

Thorax ◽

10.1136/thoraxjnl-2021-217299 ◽

2021 ◽

pp. thoraxjnl-2021-217299

Author(s):

Carla Rebeca Da Silva Sena ◽

Ediane de Queiroz Andrade ◽

Patricia de Gouveia Belinelo ◽

Elizabeth Percival ◽

Benjamin Prangemeier ◽

...

Keyword(s):

Nitric Oxide ◽

Immune Response ◽

Respiratory Symptoms ◽

Beta Agonist ◽

First Year ◽

Type 2 Immune Response ◽

Unit Increase ◽

Altered Immune Response ◽

First Year Of Life ◽

Robust Poisson Regression

BackgroundNitric oxide in exhaled air (eNO) is used as a marker of type 2 immune response-induced airway inflammation. We aimed to investigate the association between eNO and bronchiolitis incidence and respiratory symptoms in infancy, and its correlation with eosinophil protein X (EPX).MethodsWe followed up infants at 6 weeks of age born to mothers with asthma in pregnancy and measured eNO during natural sleep using a rapid response chemiluminescense analyser (CLD88; EcoMedics), collecting at least 100 breaths, interpolated for an expiratory flow of 50 mL/s. EPX normalised to creatinine was measured in urine samples (uEPX/c). A standardised questionnaire was used to measure symptoms in first year of life. Associations were investigated using multiple linear regression and robust Poisson regression models.ResultseNO levels were obtained in 184 infants, of whom 125/184 (68%) had 12 months questionnaire data available and 51/184 (28%) had uEPX/c measured. Higher eNO was associated with less respiratory symptoms during the first 6 weeks of life (n=184, ß-coefficient: –0.49, 95% CI –0.95 to –0.04, p=0.035). eNO was negatively associated with uEPX/c (ß-coefficient: –0.004, 95% CI –0.008 to –0.001, p=0.021). Risk incidence of bronchiolitis, wheeze, cold or influenza illness and short-acting beta-agonist use significantly decreased by 18%–24% for every unit increase in eNO ppb.ConclusionHigher eNO levels at 6 weeks of age may be a surrogate for an altered immune response that is associated with less respiratory symptoms in the first year of life.

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Anamnestic Immune Response in 3- to 4-year-old Children Previously Immunized With 10-valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine as 2-dose or 3-dose Priming and a Booster Dose in the First Year of Life

The Pediatric Infectious Disease Journal ◽

10.1097/inf.0b013e31821feeb7 ◽

2011 ◽

Vol 30 (9) ◽

pp. e155-e163 ◽

Cited By ~ 13

Author(s):

Sven Arne Silfverdal ◽

Helena Skerlikova ◽

Maria Zanova ◽

Danica Papúchová ◽

Magali Traskine ◽

...

Keyword(s):

Immune Response ◽

Haemophilus Influenzae ◽

Conjugate Vaccine ◽

Booster Dose ◽

First Year ◽

Nontypeable Haemophilus Influenzae ◽

First Year Of Life

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The Development of Swallowing Respiratory Coordination

Perspectives on Swallowing and Swallowing Disorders (Dysphagia) ◽

10.1044/sasd18.1.19 ◽

2009 ◽

Vol 18 (1) ◽

pp. 19-24

Author(s):

Maggie-Lee Huckabee

Keyword(s):

Cortical Activation ◽

First Year ◽

Healthy Children ◽

Nasal Airflow ◽

Single Session ◽

Primary Finding ◽

Patterns Of Behavior ◽

Cortical Modulation ◽

First Year Of Life ◽

Swallowing Apnea

Abstract Research exists that evaluates the mechanics of swallowing respiratory coordination in healthy children and adults as well and individuals with swallowing impairment. The research program summarized in this article represents a systematic examination of swallowing respiratory coordination across the lifespan as a means of behaviorally investigating mechanisms of cortical modulation. Using time-locked recordings of submental surface electromyography, nasal airflow, and thyroid acoustics, three conditions of swallowing were evaluated in 20 adults in a single session and 10 infants in 10 sessions across the first year of life. The three swallowing conditions were selected to represent a continuum of volitional through nonvolitional swallowing control on the basis of a decreasing level of cortical activation. Our primary finding is that, across the lifespan, brainstem control strongly dictates the duration of swallowing apnea and is heavily involved in organizing the integration of swallowing and respiration, even in very early infancy. However, there is evidence that cortical modulation increases across the first 12 months of life to approximate more adult-like patterns of behavior. This modulation influences primarily conditions of volitional swallowing; sleep and naïve swallows appear to not be easily adapted by cortical regulation. Thus, it is attention, not arousal that engages cortical mechanisms.

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