Epstein–Barr virus (EBV) is the first reported oncogenic virus and infects more than 90% of adults worldwide. EBV can establish a latent infection in B lymphocytes which is essential for persistence and transmission. Glycoprotein gp42 is an indispensable member of the triggering complex for EBV entry into a B cell. The N-terminal region of gp42 plays a key role in binding to gH/gL and triggering subsequent membrane fusion. However, no antibody has been reported to recognize this region and the immunogenicity of gp42 N-domain remains unknown. In the present study, we have generated a panel of nine mAbs against the gp42 N-terminal region (six mAbs to gp42-44-61aa and three mAbs to gp42-67-81aa). These mAbs show excellent binding activity and recognize different key residues locating on the gp42 N-domain. Among the nine mAbs, 4H7, 4H8 and 11G10 cross-react with rhLCV-gp42 while other mAbs specifically recognize EBV-gp42. Our newly obtained mAbs provide a useful tool for investigating the gp42 function and viral infection mechanism of γ-Herpesvirus. Furthermore, we assess the immunogenicity of the gp42 N-terminal region using the HBc149 particle as a carrier protein. The chimeric VLPs can induce high antibody titers and elicit neutralizing humoral responses to block EBV infection. More rational and effective designs are required to promote the gp42-N terminal region to become an epitope-based vaccine.

Humanized mouse models are used as comprehensive small-animal models of EBV infection. Previously, infectious doses of EBV used in vivo have been determined mainly on the basis of TD₅₀ (50% transforming dose), which is a time-consuming process. Here, we determined infectious doses of Akata-EBV-GFP using green Raji units (GRUs), and characterized dose-dependent effects in humanized mice. We defined two outcomes in vivo, including an infection model and a lymphoma model, following inoculation with low or high doses of Akata-EBV-GFP, respectively. Inoculation with a low dose induced primary B cells to become lymphoblastoid cell lines in vitro, and caused latent infection in humanized mice. In contrast, a high dose of Akata-EBV-GFP resulted in primary B cells death in vitro, and fatal B cell lymphomas in vivo. Following infection with high doses, the frequency of CD19⁺ B cells decreased, whereas the percentage of CD8⁺ T cells increased in peripheral blood and the spleen. At such doses, a small part of activated CD8⁺ T cells was EBV-specific CD8⁺ T cells. Thus, GRUs quantitation of Akata-EBV-GFP is an effective way to quantify infectious doses to study pathologies, immune response, and to assess (in vivo) the neutralizing activity of antibodies raised by immunization against EBV.

Henipaviruses are lethal zoonotic paramyxoviruses with high mortality, increasing geographic reach, and a growing number of identified species and variants. No vaccines or therapeutics are licensed for human use, creating an urgent need for effective interventions. This review highlights recent advances in neutralizing antibodies against the viral attachment (G) and fusion (F) glycoproteins, focusing on structural and mechanistic insights. Lead monoclonal antibodies target conserved epitopes and block viral entry through receptor interference or fusion inhibition. Key challenges, including narrow treatment windows and viral escape, underscore the need for rationally designed combinations and broad-spectrum, escape-resistant candidates. By consolidating current progress, we outline strategies for developing antibody therapeutics with high translational impact, serving as a first line of defense in outbreak settings and as a complementary intervention to vaccines for comprehensive henipavirus management.