SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies

SARS-CoV-2 Beta variant of concern (VOC) resists neutralization by major classes of antibodies from COVID-19 patients and vaccinated individuals. Here, serum of Beta-infected patients revealed reduced cross-neutralization of wildtype virus. From these patients, we isolated Beta-specific and cross-reactive receptor-binding domain (RBD) antibodies. The Beta-specificity results from recruitment of VOC-specific clonotypes and accommodation of mutations present in Beta and Omicron into a major antibody class that is normally sensitive to these mutations. The Beta-elicited cross-reactive antibodies share genetic and structural features with wildtype-elicited antibodies, including a public VH1-58 clonotype targeting the RBD ridge. These findings advance our understanding of the antibody response to SARS-CoV-2 shaped by antigenic drift with implications for design of next-generation vaccines and therapeutics

Minor myeloid component in Ph chromosome‐positive acute lymphoblastic leukaemia: correlation with cytogenetic pattern and implication for poor response to therapy

Morphological, immunological and cytogenetic features were studied in 27 adults presenting with Ph chromosome-positive acute lymphoblastic leukaemia (ALL), in correlation with clinical outcome. Twenty patients (group 1) were diagnosed as having typical ALL according to the FAB criteria supported by immunological findings. Less than 1% blast cells with azurophilic granules were detected in all cases. Myeloid cytochemistry, i.e. peroxidase and Sudan black-B stain, was negative in all cases. A minor phenotype deviation consisting of the expression of the CD13 myeloid-associated marker was detected in two patients. In seven patients (group 2) a diagnosis of ALL with a minor myeloid component was made because of the presence of a majority of lymphoid blasts and of 5-15% blast cells with morphological cytochemical and immunological features of the myeloid lineage. Abnormal metaphases were found in 6/20 (30%) patients in group 1, compared with 7/7 (100%) patients in group 2. All patients were treated by antilymphoid regimens; however, complete remission was achieved in 17/20 (85%) patients in group 1 versus 1/7 (14.3%) patients in group 2. Median survival was 16 months, range <1-120+ in group 1 and 9 months, range <1-15 in group 2. It is concluded that morphological, immunological and cytogenetic studies allow for the recognition of two cytological subsets of Ph+ ALL. The presence of a minor myeloid component in otherwise typical Ph chromosome-positive ALL may be associated with a distinct cytogenetic pattern and poor responses to antilymphoid therapy