Assessment of the pulmonary adaptive immune response to Cladosporium cladosporioides infection using an experimental mouse model.

Cladosporium cladosporioides causes asthma and superficial and deep infections, mostly in immunodeficient individuals and animals. This study aimed to investigate whether C. cladosporioides spores can enter the lungs through pulmonary circulation and influence pulmonary immune response. We intravenously injected mice with C. cladosporioides spore suspension and conducted several assays on the lungs. Pulmonary hemorrhage symptoms and congestion were most severe on days 1, 2, and 3 post-inoculation (PI). Extensive inflammatory cell infiltration occurred throughout the period of infection. More spores and hyphae colonizing the lungs were detected on days 1, 2, and 3 PI, and fewer spores and hyphae were observed within 21 d of infection. Numerous macrophages, dendritic cells, and neutrophils were observed on day 5 PI, along with upregulation of CD54, an intercellular adhesion molecule. Th1 and Th2 cells increased after infection; specifically, Th2 cells increased considerably on day 5 PI. These results suggest that days 2 and 5 PI represent the inflammatory peak in the lungs and that the Th2 and Th1 signaling pathways are potentially involved in pulmonary immune responses. In conclusion, the further adaptive immune responses played important roles in establishing effective pulmonary immunity against C. cladosporioides systemic infections based on innate immune responses.

Immunogenicity of biologic agents in rheumatology.

Biologic agents have become a core component of therapeutic strategies for many inflammatory rheumatic diseases. However, perhaps reflecting the specificity and generally high affinity of biologic agents, these therapeutics have been used by rheumatologists with less consideration of their pharmacokinetics than that of conventional synthetic DMARDs. Immunogenicity was recognized as a potential limitation to the use of biologic agents at an early stage in their development, although regulatory guidance was relatively limited and assays to measure immunogenicity were less sophisticated than today. The advent of biosimilars has sparked a renewed interest in immunogenicity that has resulted in the development of increasingly sensitive assays, an enhanced appreciation of the pharmacokinetic consequences of immunogenicity and the development of comprehensive and specific guidance from regulatory authorities. As a result, rheumatologists have a greatly improved understanding of the field in general, including the factors responsible for immunogenicity, its potential clinical consequences and the implications for everyday treatment. In some specialties, immunogenicity testing is becoming a part of routine clinical management, but definitive evidence of its cost-effectiveness in rheumatology is awaited.

Assessment of SARS-CoV-2 Immunity in Convalescent Children and Adolescents.

Persistence of protective immunity for SARS-CoV-2 is important against reinfection. Knowledge on SARS-CoV-2 immunity in pediatric patients is currently lacking. We opted to assess the SARS-CoV-2 adaptive immunity in recovered children and adolescents, addressing the pediatrics specific immunity towards COVID-19. Two independent assays were performed to investigate humoral and cellular immunological memory in pediatric convalescent COVID-19 patients. Specifically, RBD IgG, CD4+, and CD8+ T cell responses were identified and quantified in recovered children and adolescents. SARS-CoV-2-specific RBD IgG detected in recovered patients had a half-life of 121.6 days and estimated duration of 7.9 months compared with baseline levels in controls. The specific T cell response was shown to be independent of days after diagnosis. Both CD4+ and CD8+ T cells showed robust responses not only to spike (S) peptides (a main target of vaccine platforms) but were also similarly activated when stimulated by membrane (M) and nuclear (N) peptides. Importantly, we found the differences in the adaptive responses were correlated with the age of the recovered patients. The CD4+ T cell response to SARS-CoV-2 S peptide in children aged <12 years correlated with higher SARS-CoV-2 RBD IgG levels, suggesting the importance of a T cell-dependent humoral response in younger children under 12 years. Both cellular and humoral immunity against SARS-CoV-2 infections can be induced in pediatric patients. Our important findings provide fundamental knowledge on the immune memory responses to SARS-CoV-2 in recovered pediatric patients.

Multigene Expression Assay for Assessment of the Immune Status of Atlantic Salmon.

We report the development of a multigene gene expression assay on the BioMark HD platform for the evaluation of immune competence (ImCom) in farmed Atlantic salmon. The first version of the assay included 92 genes selected on the basis of transcriptome analyses in 54 trials that challenged the immune system; annotations were taken into account to represent the key pathways of innate and adaptive immunity. ImCom was tested on samples collected from seven independent projects. Fish were reared from the start feeding to eight months in the sea at eight units in different parts of Norway. Several tissues were analyzed. Linear discriminant analysis (LDA) showed that no more than 10 genes were required to separate groups, and a set of 46 immune genes was sufficient for any task. The second version of the assay was tested in the gills of two groups of high-performing healthy smolts and in groups with intermediate and high mortality rates (IM and HM, respectively). A set of 645 gill samples from clinically healthy Atlantic salmon was used as a reference. The IM group showed general suppression of immunity. All HM group salmon were above the threshold by the squared deviation from the reference. This group showed marked upregulation of genes involved in acute stress and inflammation: mmp-9, mmp-13, hsp70, il-1b, lect2, and cathelicidin. Further work will clarify the boundaries of the norm and explore various cases of impaired immunity.

The Immunoscore in the Clinical Practice of Patients with Colon and Rectal Cancers.

In the fine balance between tumor invasion and our defensive systems, the role played by the adaptive immune response at the tumor site is critical. Beyond the fact that all the immune components of the innate and adaptive response can be observed to varying degrees in the tumor microenvironment, it appears that a high density of T cytotoxic and memory lymphocytes, in a context of Th1 immune orientation in the tumor and its invasion front, provides a prognostic marker of paramount importance for colorectal cancer and more generally all solid tumors. The understanding of the role of immunity in cancer, tailored during one century of intensive research, has led to a complete paradigm shift.based on a sharp dissection In order to show the major impact of this conceptual revolution, we herein retrace through the example of colorectal cancer, how an effective immune test, namely the "Immunoscore", has been developed. We also provide up to date data demonstrating the capacity of the Immunoscore to prognosticate with a better accuracy than the TME classification clinical outcomes and to guide therapeutic strategies.

Development of the S3Pvac vaccine against murine Taenia crassiceps cysticercosis: a historical review.

Our work of the last 25 yr was concerned with the development of a vaccine aimed to prevent porcine Taenia solium cysticercosis and was based on cross-reacting Taenia crassiceps antigens that had proved protective against experimental intraperitoneal murine T. crassiceps cysticercosis (EIMTcC). In recent times the efficacy of the vaccine has been considered in need of confirmation, and the use of EIMTcC has been questioned as a valid tool in screening for vaccine candidates among the many antigens possibly involved. A review of our work divided in 2 parts is presented at this point, the first dealing with EIMTcC and the second with porcine T. solium cysticercosis (presented in this issue). Herein, we revise our results using EIMTcC as a measure of the protective capacity of T. crassiceps complex antigen mixtures, of purified native antigens, and of S3Pvac anti-cysticercosis vaccine composed by 3 protective peptides: GK-1, KETc1, and KETc12 either synthetic or recombinantly expressed and collectively or separately, by diverse delivery systems when administered at different doses and by different routes. Statistical analyses of the data lead confidently to the strong inference that S3Pvac is indeed an effective vaccine against EIMTcC via specific and non-specific mechanisms of protection.

Workshop on immunizations in older adults: identifying future research agendas.

Goals for immunization in older adults may differ from those in young adults and children, in whom complete prevention of disease is the objective. Often, reduced hospitalization and death but also averting exacerbation of underlying chronic illness, functional decline, and frailty are important goals in the older age group. Because of the effect of age on dendritic cell function, T cell-mediated immune suppression, reduced proliferative capacity of T cells, and other immune responses, the efficacy of vaccines often wanes with advanced age. This article summarizes the discussion and proceedings of a workshop organized by the Association of Specialty Professors, the Infectious Diseases Society of America, the American Geriatrics Society, the National Institute on Aging, and the National Institute of Allergy and Infectious Diseases. Leading researchers and clinicians in the fields of immunology, epidemiology, infectious diseases, geriatrics, and gerontology reviewed the current status of vaccines in older adults, identified knowledge gaps, and suggest priority areas for future research. The goal of the workshop was to identify what is known about immunizations (efficacy, effect, and current schedule) in older adults and to recommend priorities for future research. Investigation in the areas identified has the potential to enhance understanding of the immune process in aging individuals, inform vaccine development, and lead to more-effective strategies to reduce the risk of vaccine-preventable illness in older adults.