Biology subjects

Zumaquero, E.

Publications and source records attributed to Zumaquero, E..

4 recordsLinked to original sources

bioRxiv2026

Terminally Differentiated Influenza-Specific Effector Memory B Cells Circulate after Live Attenuated Influenza Vaccination

Live attenuated influenza vaccination (LAIV) is the only FDA approved mucosal vaccine. Easily assayed, circulating correlates of protection after LAIV are lacking. Using fluorochrome labeled hemagglutinin (HA) antigen, we previously identified a subset of HA-specific (HA+) IgDneg memory B cells that circulate after inactivated intramuscular vaccination (IIV), express the master transcriptional regulator, T-bet, as well as effector memory genes and predict durable antibody (Ab) responses to IIV. Here we profile the circulating HA+ IgDneg memory B cell response in a cohort of immunized patients who seroconvert after LAIV to identify which, if any, circulating HA+ B cells predict antibody responses after LAIV. Although we report LAIV elicits circulating T-bet+ HA+ IgDneg B cells that are phenotypically similar to those we described after IIV, we find no correlation between the magnitude of these cells and systemic HA-IgG responses after LAIV. Supervised and unsupervised analyses demonstrate that unlike IIV, LAIV preferentially elicits circulating HA+ IgDneg B cells that co-express TBX21 and the terminal effector cell gene, Zeb2. Consistent with their terminal differentiation status, LAIV-elicited T-bet+ cells cannot be recalled as short-lived antibody-secreting cells (ASCs) after systemic or mucosal antigen re-challenge. We conclude that the transcriptional profiles and functions of HA+ IgDneg B cells vary by influenza vaccine platform.

immunology↗

bioRxiv2020

Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice

The coronavirus disease 2019 (COVID-19) pandemic has highlighted the urgent need for effective preventive vaccination to reduce burden and spread of severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) in humans. Intranasal vaccination is an attractive strategy to prevent COVID-19 as the nasal mucosa represents the first-line barrier to SARS-CoV-2 entry before viral spread to the lung. Although SARS-CoV-2 vaccine development is rapidly progressing, the current intramuscular vaccines are designed to elicit systemic immunity without conferring mucosal immunity. Here, we show that AdCOVID, an intranasal adenovirus type 5 (Ad5)-vectored vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein, elicits a strong and focused immune response against RBD through the induction of mucosal IgA, serum neutralizing antibodies and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile. Therefore, AdCOVID, which promotes concomitant systemic and local mucosal immunity, represents a promising COVID-19 vaccine candidate.

immunology↗

bioRxiv2019

Fcrl5 and T-bet define influenza-specific memory B cells that predict long-lived antibody responses

Seasonal influenza vaccination elicits hemagglutinin (HA)-specific CD27+ memory B cells (Bmem) that differ in expression of T-bet, BACH2 and TCF7. T-bethiBACH2loTCF7lo Bmem are transcriptionally similar to effector-like memory cells while T-betloBACH2+TCF7+ Bmem exhibit stem-like central memory properties. T-bethi Bmem do not express plasma cell-specific transcription factors but do exhibit transcriptional, epigenetic, metabolic and functional changes that poise the cells for antibody production. Consistent with these changes, D7 HA+ T-bethi Bmem express intracellular immunoglobulin and T-bethi Bmem differentiate more rapidly into ASCs in vitro. The T-bethi Bmem response positively correlates with long-lived humoral immunity and clonotypes from T-bethi Bmem are represented in the early secondary ASC response to repeat vaccination, suggesting that this effector-like population can be used to predict vaccine durability and recall potential.

immunology↗

bioRxiv2019

IFNγ induces epigenetic programming of human T-bethi B cells and promotes TLR7/8 and IL-21 induced differentiation

Although B cells expressing the IFN{gamma}R or the IFN{gamma}-inducible transcription factor T-bet drive autoimmunity in Systemic Lupus Erythematosus (SLE)-prone mouse models, the role for IFN{gamma} signaling in human antibody responses is unknown. We show that elevated levels of IFN{gamma} in SLE patients correlate with expansion of the T-bet expressing IgDnegCD27negCD11c+CXCR5neg (DN2) pre-antibody secreting cell (pre-ASC) subset. We demonstrate that naive B cells form T-bethi pre-ASCs following stimulation with either Th1 cells or with IFN{gamma}, IL-2, anti-Ig and TLR7/8 ligand and that IL-21 dependent ASC formation is significantly enhanced by IFN{gamma} or IFN{gamma}-producing T cells. IFN{gamma} promotes ASC development by synergizing with IL-2 and TLR7/8 ligands to induce genome-wide epigenetic reprogramming of B cells, which results in increased chromatin accessibility surrounding IRF4 and BLIMP1 binding motifs and epigenetic remodeling of IL21R and PRDM1 loci. Finally, we show that IFN{gamma} signals poise B cells to differentiate by increasing their responsiveness to IL-21.

immunology↗