A central feature of the SARS-CoV-2 pandemic is that some individuals become severely ill or die, whereas others have only a mild disease course or are asymptomatic. Here we report development of an improved multimeric αβ T cell staining reagent platform, with each maxi-ferritin "spheromer" displaying 12 peptide-MHC complexes. Spheromers stain specific T cells more efficiently than peptide-MHC tetramers and capture a broader portion of the sequence repertoire for a given peptide-MHC. Analyzing the response in unexposed individuals, we find that T cells recognizing peptides conserved amongst coronaviruses are more abundant and tend to have a "memory" phenotype, compared to those unique to SARS-CoV-2. Significantly, CD8+ T cells with these conserved specificities are much more abundant in COVID-19 patients with mild disease versus those with a more severe illness, suggesting a protective role.
Copyright © 2021, American Association for the Advancement of Science.

Energetic metabolism reprogramming is critical for cancer and immune responses. Current methods to functionally profile the global metabolic capacities and dependencies of cells are performed in bulk. We designed a simple method for complex metabolic profiling called SCENITH, for single-cell energetic metabolism by profiling translation inhibition. SCENITH allows for the study of metabolic responses in multiple cell types in parallel by flow cytometry. SCENITH is designed to perform metabolic studies ex vivo, particularly for rare cells in whole blood samples, avoiding metabolic biases introduced by culture media. We analyzed myeloid cells in solid tumors from patients and identified variable metabolic profiles, in ways that are not linked to their lineage or their activation phenotype. SCENITH's ability to reveal global metabolic functions and determine complex and linked immune-phenotypes in rare cell subpopulations will contribute to the information needed for evaluating therapeutic responses or patient stratification.
Copyright © 2020 Elsevier Inc. All rights reserved.

The RV144 vaccine efficacy clinical trial showed a reduction in HIV-1 infections by 31%. Vaccine efficacy was associated with stronger binding antibody responses to the HIV Envelope (Env) V1V2 region, with decreased efficacy as responses wane. High levels of Ab-dependent cellular cytotoxicity (ADCC) together with low plasma levels of Env-specific IgA also correlated with decreased infection risk. We investigated whether B cell priming from RV144 vaccination impacted functional antibody responses to HIV-1 following infection. Antibody responses were assessed in 37 vaccine and 63 placebo recipients at 6, 12, and 36 months following HIV diagnosis. The magnitude, specificity, dynamics, subclass recognition and distribution of the binding antibody response following infection were different in RV144 vaccine recipients compared to placebo recipients. Vaccine recipients demonstrated increased IgG1 binding specifically to V1V2, as well as increased IgG2 and IgG4 but decreased IgG3 to HIV-1 Env. No difference in IgA binding to HIV-1 Env was detected between the vaccine and placebo recipients following infection. RV144 vaccination limited the development of broadly neutralizing antibodies post-infection, but enhanced Fc-mediated effector functions indicating B cell priming by RV144 vaccination impacted downstream antibody function. However, these functional responses were not associated with clinical markers of disease progression. These data reveal that RV144 vaccination primed B cells towards specific binding and functional antibody responses following HIV-1 infection.

To report a case detailing the early histopathogenesis of Burkitt lymphoma (BL), Epstein-Barr virus (EBV) positive, in the clinical setting of HIV infection.
We describe a 57 year-old woman with newly diagnosed HIV infection who presented with unilateral localized axillary lymphadenopathy. Histopathological, immunohistochemical, and flow cytometric analyses were performed and showed EBV-positive nests of Burkitt cells, including rare nests also positive for cytomegalovirus, exclusively located within hyperplastic monocytoid B-cell areas of HIV lymphadenitis. Due to positron emission tomography/computed tomography findings of persistent localized lymphadenopathy with markedly increased fludeoxyglucose avidity a core needle biopsy was performed. Histopathological, immunohistochemical, fluorescence in situ hybridization, and flow cytometric analyses confirmed BL.
Early histopathogenesis of HIV-associated BL occurred as nests of EBV-positive Burkitt cells within prominent monocytoid B-cell areas in our case. The results equip the pathologist to identify a very subtle Burkitt microlymphoma which would allow for prompt and appropriate chemotherapeutic intervention and may promote research into the possible relationship between monocytoid B cells and BL.
© 2016 John Wiley & Sons Ltd.