Immunogenicity of a Third Dose of BNT162b2 Vaccine among Lung Transplant Recipients-A Prospective Cohort Study.

Two doses of mRNA SARS-CoV-2 vaccines elicit an attenuated humoral immune response among immunocompromised patients. Our study aimed to assess the immunogenicity of a third dose of the BNT162b2 vaccine among lung transplant recipients (LTRs). We prospectively evaluated the humoral response by measuring anti-spike SARS-CoV-2 and neutralizing antibodies in 139 vaccinated LTRs ~4-6 weeks following the third vaccine dose. The t-cell response was evaluated by IFNγ assay. The primary outcome was the seropositivity rate following the third vaccine dose. Secondary outcomes included: positive neutralizing antibody and cellular immune response rate, adverse events, and COVID-19 infections. Results were compared to a control group of 41 healthcare workers. Among LTRs, 42.4% had a seropositive antibody titer, and 17.2% had a positive t-cell response. Seropositivity was associated with younger age (t = 3.736, p < 0.001), higher GFR (t = 2.355, p = 0.011), and longer duration from transplantation (t = -1.992, p = 0.024). Antibody titer positively correlated with neutralizing antibodies (r = 0.955, p < 0.001). The current study may suggest the enhancement of immunogenicity by using booster doses. Since monoclonal antibodies have limited effectiveness against prevalent sub-variants and LTRs are prone to severe COVID-19 morbidity, vaccination remains crucial for this vulnerable population.

Non-random length distribution of individual telomeres in immunodeficiency, centromeric instability and facial anomalies syndrome, type I.

Mutations in the de novo DNA methyltransferase DNMT3B lead to Immunodeficiency, Centromeric Instability and Facial anomalies (ICF) syndrome, type I. This syndrome is characterized, among other hypomethylated genomic loci, by severe subtelomeric hypomethylation that is associated with abnormally short telomere length. While it was demonstrated that the mean telomere length is significantly shorter in ICF type I cells, it is unknown whether all telomeres are equally vulnerable to shortening. To study this question we determined by combined telomere-FISH and spectral karyotyping the relative length of each individual telomere in lymphoblastoid cell lines (LCLs) generated from multiple ICF syndrome patients and control individuals. Here we confirm the short telomere lengths, and demonstrate that telomere length variance in the ICF patient group is much larger than in the control group, suggesting that not all telomeres shorten in a uniform manner. We identified a subgroup of telomeres whose relatively short lengths can distinguish with a high degree of certainty between a control and an ICF metaphase, proposing that in ICF syndrome cells, certain individual telomeres are consistently at greater risk to shorten than others. The majority of these telomeres display high sequence identity at the distal 2 kb of their subtelomeres, suggesting that the attenuation in DNMT3B methylation capacity affects individual telomeres to different degrees based, at least in part, on the adjacent subtelomeric sequence composition.