Biology subjects

Bean, D. J.

Publications and source records attributed to Bean, D. J..

3 recordsLinked to original sources

bioRxiv2024

Recent Endemic Coronavirus Infection Associates With Higher SARS-CoV-2 Cross-Reactive Fc Receptor Binding Antibodies

Recent documented infection with an endemic coronavirus (eCoV) associates with less severe coronavirus disease 2019 (COVID-19), yet the immune mechanism behind this protection has not been fully explored. We measured both antibody and T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in SARS-CoV-2 naive individuals classified into two groups, either with or without presumed recent eCoV infections. There was no difference in neutralizing antibodies and T cell responses against SARS-CoV-2 antigens between the two groups. SARS-CoV-2 naive individuals with recent presumed eCoV infection, however, had higher levels of Fc receptor (FcR) binding antibodies against eCoV spikes (S) and SARS-CoV-2 S2. There was also a significant correlation between eCoV and SARS-CoV-2 FcR binding antibodies. Recent eCoV infection boosts cross-reactive antibodies that can mediate Fc effector functions, and this may play a role in the observed heterotypic immune protection against severe COVID-19.

immunology↗

bioRxiv2023

Heterotypic responses against nsp12/nsp13 from prior SARS-CoV-2 infection associates with lower subsequent endemic coronavirus incidence

Immune responses from prior SARS-CoV-2 infection and COVID-19 vaccination do not prevent re-infections and may not protect against future novel coronaviruses (CoVs). We examined the incidence of and immune differences against human endemic CoVs (eCoV) as a proxy for response against future emerging CoVs. Assessment was among those with known SARS-CoV-2 infection, COVID-19 vaccination but no documented SARS-CoV-2 infection, or neither exposure. Retrospective cohort analyses suggest that prior SARS-CoV-2 infection, but not COVID-19 vaccination alone, protects against subsequent symptomatic eCoV infection. CD8+ T cell responses to the non-structural eCoV proteins, nsp12 and nsp13, were significantly higher in individuals with previous SARS-CoV-2 infection as compared to the other groups. The three groups had similar cellular responses against the eCoV spike and nucleocapsid, and those with prior spike exposure had lower eCoV-directed neutralizing antibodies. Incorporation of non-structural viral antigens in a future pan-CoV vaccine may improve protection against future heterologous CoV infections.

immunology↗

bioRxiv2021

Differentiation of exhausted CD8 T cells after termination of chronic antigen stimulation stops short of achieving functional T cell memory

T cell exhaustion is associated with failure to clear chronic infections and malignant cells. Defining the molecular mechanisms of T cell exhaustion and reinvigoration is essential to improving immunotherapeutic modalities. Analysis of antigen-specific CD8+ T cells before and after antigen removal in human hepatitis C virus (HCV) infection confirmed pervasive phenotypic, functional, and transcriptional differences between exhausted and memory CD8+ T cells. After viral cure, we observed broad phenotypic and transcriptional changes in clonally stable exhausted T-cell populations suggesting differentiation towards a memory-like profile. However, functionally, the cells showed little improvement and critical transcriptional regulators remained in the exhaustion state. Notably, T cells from chronic HCV infection that were exposed to antigen for shorter periods of time because of viral escape mutations were functionally and transcriptionally more similar to memory T cells from spontaneously resolved acute HCV infection. Thus, duration of T cell stimulation impacts the ability to recover from exhaustion, as antigen removal after long-term T cell exhaustion is insufficient for the development of key T cell memory characteristics.

immunology↗