Cunha, D. | Search bioRxiv

bioRxiv2026

Extracellular vesicles from antigen-activated B cells stimulate oncogenic herpesvirus lytic gene expression

B cell-derived extracellular vesicles (B-EVs) have been associated with immunomodulatory functions like antigen presentation, cytokine signaling, and T cell activation. However, little is known about the general composition of B-EVs or how the state of the donor cells affects the B-EV composition or functions. We performed integrated proteomic, lipidomic, and transcriptomic analyses of EVs secreted by B cells in resting conditions or upon 30 min of B cell receptor (BCR) activation. Antigen-driven BCR stimulation led to acute remodeling of the protein and lipid composition, and RNA cargo of the B-EVs, which also translated into differential responses in recipient B cells. Remarkably, EVs from activated B cells stimulated lytic gene expression of latent oncogenic {gamma}-herpesviruses Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV). These findings suggest a novel mechanism for the potentially oncogenic reactivation of these lifelong-persisting latent herpesviruses, residing in B cells. Our results support a mechanism in which, upon immune activation, B-EVs from antigen-specific B cells induce viral reactivation in bystander B cells in a paracrine manner, providing molecular insights that bridge immune activation and the pathogenesis of {gamma}-herpesvirus infections.

immunology↗

bioRxiv2020

A recombinant protein SARS-CoV-2 candidate vaccine elicits high-titer neutralizing antibodies in macaques.

Vaccines that generate robust and long-lived protective immunity against SARS-CoV-2 infection are urgently required. We assessed the potential of vaccine candidates based on the SARS-CoV-2 spike in cynomolgus macaques (M. fascicularis) by examining their ability to generate spike binding antibodies with neutralizing activity. Antigens were derived from two distinct regions of the spike S1 subunit, either the N-terminal domain (NTD) or an extended C-terminal domain containing the receptor-binding domain (RBD) and were fused to the human IgG1 Fc domain. Three groups of 2 animals each were immunized with either antigen, alone or in combination. The development of antibody responses was evaluated through 20 weeks post-immunization. A robust IgG response to the spike protein was detected as early as 2 weeks after immunization with either protein and maintained for over 20 weeks. Sera from animals immunized with antigens derived from the RBD were able to prevent binding of soluble spike proteins to the ACE2 receptor, shown by in vitro binding assays, while sera from animals immunized with the NTD alone lacked this activity. Crucially, sera from animals immunized with the RBD but not the NTD had potent neutralizing activity against SARS-CoV-2 pseudotyped virus, with titers in excess of 10,000, greatly exceeding that typically found in convalescent humans. Neutralizing activity persisted for more than 20 weeks. These data support the utility of spike subunit-based antigens as a vaccine for use in humans.

immunology↗