Biology subjects

Tobian, A. A.

Publications and source records attributed to Tobian, A. A..

4 recordsLinked to original sources

bioRxiv2026

CD11c+ myeloid cells are the predominant CD4+CCR5+ immune population in the foreskin and are increased in men with HIV-associated penile anaerobes

Specific anaerobic species within the penile microbiome - Bacteria Associated with Seroconversion, Inflammation and Immune Cells (BASIC) - have been linked to increased HIV-1 susceptibility. These bacteria can directly disrupt epithelial integrity and are believed to increase local inflammation, resulting in an increased density of HIV-susceptible T cells in the inner foreskin. It is currently unknown whether other immune cells bearing the HIV entry receptors, CD4 and CCR5, are also elevated in individuals with a high abundance of BASIC species. Using inner foreskin tissues and penile swabs from males undergoing voluntary medical male circumcision, we performed a retrospective cross-sectional study to assess the relationship between BASIC species and the tissue density of such immune cells, including CD68+ macrophages, CD11c+ dendritic cells, and CD207+ Langerhans cells. The most abundant cells in the inner foreskin expressing the HIV co-receptors were CD11c+ dendritic cells (48.6% of CD4+/CCR5+ cells), followed by CD68+ macrophages (28.6%), CD3+ T cells (18.8%), and CD207+ Langerhans-like (8.8%) cells. The absolute abundance of BASIC species was associated with elevated tissue densities of both CD4+/CCR5+ T cells (as previously reported) and a heterogeneous population of CD3-/CD4+/CCR5+ cells of myeloid origin. In the dermis, BASIC species abundance was linked to elevated densities of cells expressing CD11c, CD68, and CD207, as well as those co-expressing CD11c and CD207; furthermore, CD11c+ and CD207+ cells were farther from the basement membrane in participants with a high abundance of BASIC species. Myeloid cells were not elevated in participants with a high abundance of control taxa. In an integrated analysis including previously published data from this same cohort, myeloid-cell densities clustered tightly together, positively correlated with BASIC species and pro-inflammatory cytokines, and had trends to negative correlations with control taxa (significant for CD207+ cell density). Overall, our findings suggest that BASIC species are associated with a broader foreskin immune phenotype marked by increased densities of HIV-susceptible myeloid and T cells, alongside epithelial disruption.

immunology↗

bioRxiv2021

Minimal cross-over between mutations associated with Omicron variant of SARS-CoV-2 and CD8+ T cell epitopes identified in COVID-19 convalescent individuals

There is a growing concern that ongoing evolution of SARS-CoV-2 could lead to variants of concern (VOC) that are capable of avoiding some or all of the multi-faceted immune response generated by both prior infection or vaccination, with the recently described B.1.1.529 (Omicron) VOC being of particular interest. Peripheral blood mononuclear cell samples from PCR-confirmed, recovered COVID-19 convalescent patients (n=30) infected with SARS-CoV-2 in the United States collected in April and May 2020 who possessed at least one or more of six different HLA haplotypes were selected for examination of their anti-SARS-CoV-2 CD8+ T-cell responses using a multiplexed peptide-MHC tetramer staining approach. This analysis examined if the previously identified viral epitopes targeted by CD8+ T-cells in these individuals (n=52 distinct epitopes) are mutated in the newly described Omicron VOC (n=50 mutations). Within this population, only one low-prevalence epitope from the Spike protein restricted to two HLA alleles and found in 2/30 (7%) individuals contained a single amino acid change associated with the Omicron VOC. These data suggest that virtually all individuals with existing anti-SARS-CoV-2 CD8+ T-cell responses should recognize the Omicron VOC, and that SARS-CoV-2 has not evolved extensive T-cell escape mutations at this time. ImportanceThe newly identified Omicron variant of concern contains more mutations than any of the previous variants described to date. In addition, many of the mutations associated with the Omicron variant are found in areas that are likely bound by neutralizing antibodies, suggesting that the first line of immunological defense against COVID-19 may be compromised. However, both natural infection and vaccination develop T-cell based responses, in addition to antibodies. This study examined if the parts of the virus, or epitopes, targeted by the CD8+ T-cell response in thirty individuals who recovered from COVID-19 in 2020 were mutated in the Omicron variant. Only one of 52 epitopes identified in this population contained an amino acid that was mutated in Omicron. These data suggest that the T-cell immune response in previously infected, and most likely vaccinated individuals, should still be effective against Omicron.

immunology↗

bioRxiv2020

CD8+ T cell responses in convalescent COVID-19 individuals target epitopes from the entireSARS-CoV-2 proteome and show kinetics of early differentiation

Characterization of the T cell response in individuals who recover from SARS-CoV-2 infection is critical to understanding its contribution to protective immunity. A multiplexed peptide-MHC tetramer approach was used to screen 408 SARS-CoV-2 candidate epitopes for CD8+ T cell recognition in a cross-sectional sample of 30 COVID-19 convalescent individuals. T cells were evaluated using a 28-marker phenotypic panel, and findings were modelled against time from diagnosis, humoral and inflammatory responses. 132 distinct SARS-CoV-2-specific CD8+ T cell epitope responses across six different HLAs were detected, corresponding to 52 unique reactivities. T cell responses were directed against several structural and non-structural virus proteins. Modelling demonstrated a coordinated and dynamic immune response characterized by a decrease in inflammation, increase in neutralizing antibody titer, and differentiation of a specific CD8+ T cell response. Overall, T cells exhibited distinct differentiation into stem-cell and transitional memory states, subsets, which may be key to developing durable protection.

immunology↗

bioRxiv2020

A rapid, point of care red blood cell agglutination assay for detecting antibodies against SARS-CoV-2

The COVID-19 pandemic has brought the world to a halt, with cases observed around the globe causing significant mortality. There is an urgent need for serological tests to detect antibodies against SARS-CoV-2, which could be used to assess the prevalence of infection, as well as ascertain individuals who may be protected from future infection. Current serological tests developed for SARS-CoV-2 rely on traditional technologies such as enzyme-linked immunosorbent assays (ELISA) and lateral flow assays, which may lack scalability to meet the demand of hundreds of millions of antibody tests in the coming year. Herein, we present an alternative method of antibody testing that just depends on one protein reagent being added to patient serum/plasma or whole blood and a short five-minute assay time. A novel fusion protein was designed that binds red blood cells (RBC) via a single-chain variable fragment (scFv) against the H antigen and displays the receptor-binding domain (RBD) of SARS-CoV-2 spike protein on the surface of RBCs. Upon mixing of the fusion protein, RBD-scFv with recovered COVID-19 patient serum and RBCs, we observed agglutination of RBCs, indicating the patient developed antibodies against SARS-CoV-2 RBD. Given that the test uses methods routinely used in hospital clinical labs across the world, we anticipate the test can be rapidly deployed with only the protein reagent required at projected manufacturing cost at U.S. cents per test. We anticipate our agglutination assay may find extensive use in low-resource settings for detecting SARS-CoV-2 antibodies.Competing Interest StatementR.L.K. is an inventor on a provisional patent application related to the work described in the manuscript. All other authors have no competing interests.View Full Text

pathology↗