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The impact of exposure to air pollutants, such as fine particulate matter (PM), on the immune system and its consequences on pediatric asthma are not well understood. We investigated whether the ambient levels of fine PM with aerodynamic diameter ≤ 2.5 microns (PM ) are associated with alterations in circulating monocytes in children with or without asthma. Increased exposure to ambient PM was linked to specific monocyte subtypes, particularly in children with asthma. Mechanistically, we hypothesized that innate trained immunity is evoked by a primary exposure to fine PM and accounts for an enhanced inflammatory response after secondary stimulation in vitro. We determined that the trained immunity was induced in circulating monocytes by fine particulate pollutants, and it was characterized by upregulation of proinflammatory mediators, such as TNF, IL-6, and IL-8, upon stimulation with house dust mite or LPS. This phenotype was epigenetically controlled by enhanced H3K27ac marks in circulating monocytes. The specific alterations of monocytes after ambient pollution exposure suggest a possible prognostic immune signature for pediatric asthma, and pollution-induced trained immunity may provide a potential therapeutic target for asthmatic children living in areas with increased air pollution.

While food allergy oral immunotherapy (OIT) can provide safe and effective desensitization (DS), the immune mechanisms underlying development of sustained unresponsiveness (SU) following a period of avoidance are largely unknown. Here, we compare high dimensional phenotypes of innate and adaptive immune cell subsets of participants in a previously reported, phase 2 randomized, controlled, peanut OIT trial who achieved SU vs. DS (no vs. with allergic reactions upon food challenge after a withdrawal period; n = 21 vs. 30 respectively among total 120 intent-to-treat participants). Lower frequencies of naïve CD8

Despite the success of the BNT162b2 mRNA vaccine, the immunological mechanisms that underlie its efficacy are poorly understood. Here we analyzed the innate and adaptive responses to BNT162b2 in mice, and show that immunization stimulated potent antibody and antigen-specific T cell responses, as well as strikingly enhanced innate responses after secondary immunization, which was concurrent with enhanced serum interferon (IFN)-γ levels 1 d following secondary immunization. Notably, we found that natural killer cells and CD8

CD8(+) T cells are seldom considered in IgE mediated food allergy; we show that peanut specific CD8(+) T cells are increased in peanut allergic human subjects.

We identified a primate calicivirus (Pan-1) VPg in Pan-1-infected cells. The Pan-1 VPg was associated with both genomic and subgenomic RNAs. RNase digestion of Pan-1 RNA yielded a residual protein of 16 kDa. The N-terminal sequence of Pan-1 VPg was determined by direct amino acid sequencing and mapped to a region of the genome equivalent to picornavirus VPgs. Alignment of this protein sequence with similar regions of other calicivirus genomes allowed identification of conserved amino acid motifs and potential boundaries of the calicivirus VPg genes. Proteinase K treatment abolished the infectivity of Pan-1 RNA, suggesting that Pan-1 VPg is required for RNA infectivity.

MOLECULAR CHARACTERIZATION OF A GENETIC AND ANTIGENIC VARIANT IN THE SAPPORO GENOGROUP OF HUMAN CALICIVIRUSES. † 1031

Introduction: MX virus is a recently characterized Snow Mountain virus-like human calicivirus (HuCV) identified in stool from a Mexican child with acute gastroenteritis. The expression of the recombinant MX(rMX) capsid in baculovirus permitted the development of antigen and antibody EIAs that can be used for identification of this strain.Aim: This study describes the characterization of monoclonal antibodies (Mabs) developed against the rMX antigen.Methods: Ten Mabs to the MX virus were generated using the baculovirus-expressed rMX viral capsid as immunogen. Specificity was demonstrated by immunoprecipitation and Western blot. Enzyme immune assays(EIAs) using the Mabs were used to detect MX antigens in stools.Results: Each of the Mabs reacted with the rMX antigen and with stool specimens from 5 children infected with the MX virus, but not with the baculovirus-expressed recombinant Norwalk virus capsid. The Mabs divided into 3 groups based upon cross-reactivities in a competition EIA. Each group also revealed an unique antigen binding pattern in the immunoprecipitation and Western blot analyses. EIAs utilizing the Mabs as coating or detector antibodies were specific and sensitive for detection of MX antigens in human stools. Conclusion: The unlimited supply of the rMX Mabs will allow development of type-specific assays for clinical diagnosis as well as antigenic characterization of HuCVs.