HE DISEASE BURDEN OF SEAsonal influenza in the pediatric population is generally attributed to a combination of immunologic naivety, prolonged virus shedding, and enhanced transmission opportunity in child-care and educational institutions. 1 Consistent with this experience, initial reports of the introduction and indigenous transmission of 2009 influenza A(H1N1) infection in many countries have largely involved children, 2 often attending day or boarding schools. [3][4][5] Serosurveys have demonstrated little or no cross-reactivity of the pediatric sera sample to the new virus strain, under-Context In the ongoing influenza pandemic, a safe and effective vaccine against 2009 influenza A(H1N1) is needed for infants and children.Objective To assess the immunogenicity and safety of a 2009 influenza A(H1N1) vaccine in children.Design, Setting, and Participants Randomized, observer-blind, age-stratified, parallel group study assessing 2 doses of an inactivated, split-virus 2009 influenza A(H1N1) vaccine in 370 healthy infants and children aged 6 months to less than 9 years living in Australia.Intervention Intramuscular injection of 15 µg or 30 µg of hemagglutinin antigen dose of monovalent, unadjuvanted 2009 influenza A(H1N1) vaccine in a 2-dose regimen, administered 21 days apart.Main Outcome Measures Hemagglutination inhibition assay to estimate the proportion of participants with antibody titers of 1:40 or greater, seroconversion, or a significant antibody titer increase, and factor increase in geometric mean titer. Assessments of solicited adverse events during 7 days and unsolicited adverse events for 21 days after each vaccination. ResultsFollowing the first dose of vaccine, antibody titers of 1:40 or greater were observed in 161 of 174 infants and children in the 15-µg group (92.5%; 95% confidence interval [CI], 87.6%-95.6%) and in 168 of 172 infants and children in the 30-µg group (97.7%; 95% CI, 94.2%-99.1%). Corresponding seroconversion rates were 86.8% (95% CI, 80.9%-91.0%) and 94.2% (95% CI, 89.6%-96.8%), and factor increases in geometric mean titer were 13.6 (95% CI,). All participants demonstrated antibody titers of 1:40 or greater after the second vaccine dose. Immune responses were robust regardless of age, baseline serostatus, or seasonal influenza vaccination status. The majority of adverse events were mild to moderate in severity. ConclusionOne 15-µg dose of vaccine was immunogenic in infants and children starting at 6 months of age and vaccine-associated reactions were mild to moderate in severity. Trial Registration clinicaltrials.gov Identifier: NCT00940108

Hodgkin lymphoma is characterized by an extensively dominant tumor microenvironment (TME) composed of different types of noncancerous immune cells with rare malignant cells. Characterization of the cellular components and their spatial relationship is crucial to understanding cross-talk and therapeutic targeting in the TME. We performed single-cell RNA sequencing of more than 127,000 cells from 22 Hodgkin lymphoma tissue specimens and 5 reactive lymph nodes, profi ling for the fi rst time the phenotype of the Hodgkin lymphoma-specifi c immune microenvironment at single-cell resolution. Single-cell expression profi ling identifi ed a novel Hodgkin lymphoma-associated subset of T cells with prominent expression of the inhibitory receptor LAG3, and functional analyses established this LAG3 + T-cell population as a mediator of immunosuppression. Multiplexed spatial assessment of immune cells in the microenvironment also revealed increased LAG3 + T cells in the direct vicinity of MHC class II-defi cient tumor cells. Our fi ndings provide novel insights into TME biology and suggest new approaches to immune-checkpoint targeting in Hodgkin lymphoma. SIGNIFICANCE:We provide detailed functional and spatial characteristics of immune cells in classic Hodgkin lymphoma at single-cell resolution. Specifi cally, we identifi ed a regulatory T-cell-like immunosuppressive subset of LAG3 + T cells contributing to the immune-escape phenotype. Our insights aid in the development of novel biomarkers and combination treatment strategies targeting immune checkpoints.

on behalf of the PAEDS-ACE Investigators abstract OBJECTIVE: We aimed to describe the clinical features and outcome of human parechovirus (HPeV) encephalitis cases identified by the Australian Childhood Encephalitis (ACE) study.

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β-Adrenergic receptor (βAR) signaling regulates many physiological processes, including immune system responses. There is growing evidence also for βAR-induced modulation of cancer growth and metastasis. In the Eμ-myc mouse model of B-cell lymphoma, we investigated the effects of chronically elevated βAR signaling on lymphoma progression and antitumor immunity, as well as the impact on cancer immunotherapy. Chronic treatment with the nonselective β-agonist isoprenaline promoted lymphoma development in a manner dependent on signaling within the hematopoietic compartment. βAR signaling significantly suppressed the proliferation, IFNγ production, and cytolytic killing capacity of antigen-specific CD8 T cells. This inhibited CD8 T-cell responses to immune modulating antibodies, including anti-PD-1 and anti-4-1BB, resulting in less effective control of lymphoma. The inhibitory effects on CD8 T cells occurred independently of changes to DC function and included direct suppression of CD8 T-cell stimulation. The suppressive effects of chronic βAR signaling on antitumor effector cells was selective to T cells, as it did not perturb the innate lymphocyte response to an experimental NKT cell-targeting vaccine, in a setting where innate immune control is dependent on NKT cell and NK cell activation. These findings demonstrate that chronic βAR signaling has an immunosuppressive effect on CD8 T cells, which decreases the efficacy of CD8 T cell-targeting immunotherapies. These findings identify βAR signaling as a target for modulation during cancer immunotherapy that may increase therapeutic response and improve patient outcomes. .

Highlights d TBL1XR1 mutation skews the humoral immune response toward producing memory B cells d TBL1XR1 mutant memory cells feature aberrant cyclic reentry to new germinal centers d Mutant TBL1XR1 acts by triggering aberrant targeting of SMRT complex to BACH2 d TBL1XR1 mutation gives rise to extranodal ABC-DLBCLs derived from memory B cells

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Most severe pertussis occurred in young, unimmunized infants, although severe disease was also observed in children >12 months of age and previously vaccinated children. Children admitted with pertussis with evidence of coinfection, history of prematurity or fever on presentation need close monitoring.