SARS-CoV-2 infection in children and implications for vaccination.

The COVID-19 pandemic caused by novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for more than 500 million cases worldwide as of April 2022. Initial estimates in 2020 found that children were less likely to become infected with SARS-CoV-2 and more likely to be asymptomatic or display mild COVID-19 symptoms. Our early understanding of COVID-19 transmission and disease in children led to a range of public health measures including school closures that have indirectly impacted child health and wellbeing. The emergence of variants of concern (particularly Delta and Omicron) has raised new issues about transmissibility in children, as preliminary data suggest that children may be at increased risk of infection, especially if unvaccinated. Global national prevalence data show that SARS-CoV-2 infection in children and adolescents is rising due to COVID-19 vaccination among adults and increased circulation of Delta and Omicron variants. To mitigate this, childhood immunisation programmes are being implemented globally to prevent direct and indirect consequences of COVID-19 including severe complications (e.g., MIS-C), debilitating long-COVID symptoms, and the indirect impacts of prolonged community and school closures on childhood education, social and behavioural development and mental health. This review explores the current state of knowledge on COVID-19 in children including COVID-19 vaccination strategies. IMPACT: Provides an up-to-date account of SARS-CoV-2 infections in children. Discusses the direct and indirect effects of COVID-19 in children. Provides the latest information on the current state of global COVID-19 vaccination in children.

Evaluating Functional Immunity Following Encapsulated Bacterial Infection and Vaccination.

Encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis cause significant morbidity and mortality in young children despite the availability of vaccines. Highly specific antibodies are the primary mechanism of protection against invasive disease. Robust and standardised assays that measure functional antibodies are also necessary for vaccine evaluation and allow for the accurate comparison of data between clinical studies. This mini review describes the current state of functional antibody assays and their importance in measuring protective immunity.

An Improved and High Throughput Respiratory Syncytial Virus (RSV) Micro-neutralization Assay.

Respiratory syncytial virus-specific neutralizing antibodies (RSV NAbs) are an important marker of protection against RSV. A number of different assay formats are currently in use worldwide so there is a need for an accurate and high-throughput method for measuring RSV NAbs. We describe here an imaging-based micro-neutralization assay that has been tested on RSV subgroup A and can also be adapted for RSV subgroup B and different sample types. This method is highly reproducible, with inter-assay variations for the reference antiserum being less than 10%. We believe this assay can be readily established in many laboratories worldwide at relatively low cost. Development of an improved, high-throughput assay that measures RSV NAbs represents a significant step forward for the standardization of this method internationally as well as being critical for the evaluation of novel RSV vaccine candidates in the future.

Effect of peripheral blood mononuclear cell cryopreservation on innate and adaptive immune responses.

Cryopreservation of blood-derived immune cells is commonly used in clinical trials to examine immunological responses. However, studies elucidating the effects of cryopreservation on peripheral blood mononuclear cell (PBMC) responses have shown inconsistent results making it difficult to draw meaningful conclusions. Therefore we sought to address this issue by comparing key innate and adaptive immune parameters between freshly-isolated and cryopreserved PBMCs from healthy adults. We examined the effect of cryopreservation on the expression of key markers on innate and adaptive immune cell populations (i.e. CD4+ and CD8+ [T cells], CD14+ [monocytes], CD19+ [B cells], CD56+ [NK cells] or CD19 + CD27+ [memory B cells]), on cytokine secretion (TNF-α, INF-γ, IL-1ß, IL-10, IL-6, MCP-1 and RANTES) in cultured PBMC supernatants following stimulation with a range of Toll-like receptor (TLR) agonists, as well as on antigen-specific memory B cell enumeration by ELISpot. We found that cryopreservation had no effect on the expression of immune markers on innate and adaptive immune cells as well on the number of antigen-specific memory B cells. However, the response to TLR ligands such as FLA-ST, CpG and LPS was variable with increased cytokine production by cryopreserved PBMCs observed compared to freshly-isolated PBMCs. Our results suggest that the effect of cryopreservation on the biological response of immune cell populations needs to be carefully considered, particularly in the context of clinical studies that rely on these immune outcomes.

The contrasting roles of Th17 immunity in human health and disease.

The human immune system is a tightly regulated network that protects the host from disease. An important aspect of this is the balance between pro-inflammatory Th17 cells and anti-inflammatory T regulatory (Treg) cells in maintaining immune homeostasis. Foxp3+ Treg are critical for sustaining immune tolerance through IL-10 and transforming growth factor-ß while related orphan receptor-γt+ Th17 cells promote immunopathology and auto-inflammatory diseases through the actions of IL-17A, IL-21 and IL-22. Therefore, imbalance between Treg and Th17 cells can result in serious pathology in many organs and tissues. Recently, certain IL-17-producing cells have been found to be protective against infectious disease, particularly in relation to extracellular bacteria such Streptococcus pneumoniae; a number of other novel IL-17-secreting cell populations have also been reported to protect against a variety of other pathogens. In this mini-review, the dual roles of Treg and Th17 cells are discussed in the context of autoimmunity and infections, highlighting recent advances in the field. Development of novel strategies specifically designed to target these critical immune response pathways will become increasingly important in maintenance of human health.

Anti-Inflammatory Effects of Vitamin D on Human Immune Cells in the Context of Bacterial Infection.

Vitamin D induces a diverse range of biological effects, including important functions in bone health, calcium homeostasis and, more recently, on immune function. The role of vitamin D during infection is of particular interest given data from epidemiological studies suggesting that vitamin D deficiency is associated with an increased risk of infection. Vitamin D has diverse immunomodulatory functions, although its role during bacterial infection remains unclear. In this study, we examined the effects of 1,25(OH)2D3, the active metabolite of vitamin D, on peripheral blood mononuclear cells (PBMCs) and purified immune cell subsets isolated from healthy adults following stimulation with the bacterial ligands heat-killed pneumococcal serotype 19F (HK19F) and lipopolysaccharide (LPS). We found that 1,25(OH)2D3 significantly reduced pro-inflammatory cytokines TNF-α, IFN-γ, and IL-1ß as well as the chemokine IL-8 for both ligands (three- to 53-fold), while anti-inflammatory IL-10 was increased (two-fold, p = 0.016) in HK19F-stimulated monocytes. Levels of HK19F-specific IFN-γ were significantly higher (11.7-fold, p = 0.038) in vitamin D-insufficient adults (<50 nmol/L) compared to sufficient adults (>50 nmol/L). Vitamin D also shifted the pro-inflammatory/anti-inflammatory balance towards an anti-inflammatory phenotype and increased the CD14 expression on monocytes (p = 0.008) in response to LPS but not HK19F stimulation. These results suggest that 1,25(OH)2D3 may be an important regulator of the inflammatory response and supports further in vivo and clinical studies to confirm the potential benefits of vitamin D in this context.