Booster Dose of SARS-CoV-2 mRNA Vaccine in Kidney Transplanted Patients Induces Wuhan-Hu-1 Specific Neutralizing Antibodies and T Cell Activation but Lower Response against Omicron Variant.

Kidney transplanted recipients (KTR) are at high risk of severe SARS-CoV-2 infection due to immunosuppressive therapy. Although several studies reported antibody production in KTR after vaccination, data related to immunity to the Omicron (B.1.1.529) variant are sparse. Herein, we analyzed anti-SARS-CoV-2 immune response in seven KTR and eight healthy controls after the second and third dose of the mRNA vaccine (BNT162b2). A significant increase in neutralizing antibody (nAb) titers were detected against pseudoviruses expressing the Wuhan-Hu-1 spike (S) protein after the third dose in both groups, although nAbs in KTR were lower than controls. nAbs against pseudoviruses expressing the Omicron S protein were low in both groups, with no increase after the 3rd dose in KTR. Reactivity of CD4+ T cells after boosting was observed when cells were challenged with Wuhan-Hu-1 S peptides, while Omicron S peptides were less effective in both groups. IFN-γ production was detected in KTR in response to ancestral S peptides, confirming antigen-specific T cell activation. Our study demonstrates that the 3rd mRNA dose induces T cell response against Wuhan-Hu-1 spike peptides in KTR, and an increment in the humoral immunity. Instead, humoral and cellular immunity to Omicron variant immunogenic peptides were low in both KTR and healthy vaccinated subjects.

In-silico evaluation of adenoviral COVID-19 vaccination protocols: Assessment of immunological memory up to 6 months after the third dose.

Background: The immune response to adenoviral COVID-19 vaccines is affected by the interval between doses. The optimal interval is unknown. Aim: We aim to explore in-silico the effect of the interval between vaccine administrations on immunogenicity and to analyze the contribution of pre-existing levels of antibodies, plasma cells, and memory B and T lymphocytes. Methods: We used a stochastic agent-based immune simulation platform to simulate two-dose and three-dose vaccination protocols with an adenoviral vaccine. We identified the model's parameters fitting anti-Spike antibody levels from individuals immunized with the COVID-19 vaccine AstraZeneca (ChAdOx1-S, Vaxzevria). We used several statistical methods, such as principal component analysis and binary classification, to analyze the correlation between pre-existing levels of antibodies, plasma cells, and memory B and T cells to the magnitude of the antibody response following a booster dose. Results and conclusions: We find that the magnitude of the antibody response to a booster depends on the number of pre-existing memory B cells, which, in turn, is highly correlated to the number of T helper cells and plasma cells, and the antibody titers. Pre-existing memory T cytotoxic cells and antibodies directly influence antigen availability hence limiting the magnitude of the immune response. The optimal immunogenicity of the third dose is achieved over a large time window, spanning from 6 to 16 months after the second dose. Interestingly, after any vaccine dose, individuals can be classified into two groups, sustainers and decayers, that differ in the kinetics of decline of their antibody titers due to differences in long-lived plasma cells. This suggests that the decayers may benefit from a tailored boosting schedule with a shorter interval to avoid the temporary loss of serological immunity.

Identification of functional pathways and molecular signatures in neuroendocrine neoplasms by multi-omics analysis.

BACKGROUND: Neuroendocrine neoplasms (NENs) represent a heterogeneous class of rare tumors with increasing incidence. They are characterized by the ability to secrete peptide hormones and biogenic amines but other reliable biomarkers are lacking, making diagnosis and identification of the primary site very challenging. While in some NENs, such as the pancreatic ones, next generation sequencing technologies allowed the identification of new molecular hallmarks, our knowledge of the molecular profile of NENs from other anatomical sites is still poor. METHODS: Starting from the concept that NENs from different organs may be clinically and genetically correlated, we applied a multi-omics approach by combining multigene panel testing, CGH-array, transcriptome and miRNome profiling and computational analyses, with the aim to highlight common molecular and functional signatures of gastroenteropancreatic (GEP)-NENs and medullary thyroid carcinomas (MTCs) that could aid diagnosis, prognosis and therapy. RESULTS: By comparing genomic and transcriptional profiles, ATM-dependent signaling emerged among the most significant pathways at multiple levels, involving gene variations and miRNA-mediated regulation, thus representing a novel putative druggable pathway in these cancer types. Moreover, a set of circulating miRNAs was also selected as possible diagnostic/prognostic biomarkers useful for clinical management of NENs. CONCLUSIONS: These findings depict a complex molecular and functional landscape of NENs, shedding light on novel therapeutic targets and disease biomarkers to be exploited.

Molecular characterization of an analphoid supernumerary marker chromosome derived from 18q22.1➔qter in prenatal diagnosis: a case report.

BACKGROUND: Small supernumerary marker chromosomes (sSMC) occur in 0.072% of unselected cases of prenatal diagnoses, and their molecular cytogenetic characterization is required to establish a reliable karyotype-phenotype correlation. A small group of sSMC are C-band-negative and devoid of alpha-satellite DNA. We report the molecular cytogenetic characterization of a de novo analphoid sSMC derived from 18q22.1→qter in cultured amniocytes. RESULTS: We identified an analphoid sSMC in cultured amniocytes during a prenatal diagnosis performed because of advanced maternal age. GTG-banding revealed an sSMC in all metaphases. FISH experiments with a probe specific for the chromosome 18 centromere, and C-banding revealed neither alphoid sequences nor C-banding-positive satellite DNA thereby suggesting the presence of a neocentromere. To characterize the marker in greater detail, we carried out additional FISH experiments with a set of appropriate BAC clones. The pattern of the FISH signals indicated a symmetrical organization of the marker, the breakpoint likely representing the centromere of an inverted duplicated chromosome that results in tetrasomy of 18q22.1→qter. The karyotype after molecular cytogenetic investigations was interpreted as follows: 47,XY,+inv dup(18)(qter→q22.1::q22.1→neo→qter). CONCLUSION: Our case is the first report, in the prenatal diagnosis setting, of a de novo analphoid marker chromosome originating from the long arm of chromosome 18, and the second report of a neocentromere formation at 18q22.1.