biostudies-literatureUnknown16(1)Wang GThe global prevalence and disease burden of alphaherpesviruses infections, including human-infecting viruses such as HSV-1, HSV-2, and VZV, as well as animal-infecting viruses like PRV, BHV, CHV, and FHV, highlight the unmet need for more effective and universal antiviral strategies. However, there has been no significant progress in developing broad-spectrum interventions against herpesvirus. Here we report the identification of a broadly neutralizing antibody against alphaherpesviruses, 16F9, which targets the glycoprotein B (gB) of alphaherpesviruses and offers cross-protection against multiple viruses such as HSV-1, HSV-2, and PRV in mice. 16F9 demonstrated robust therapeutic efficacy in various female mouse models of herpesvirus diseases including PRV-induced viral encephalitis, HSV-1Nature communications11144https://www.ebi.ac.uk/biostudies/studies/S-EPMC12708680biostudies-literatureA broadly neutralizing antibody confers cross-genus protection against alphaherpesviruses by inhibiting gB-mediated membrane fusion.PMC12708680Huang CLiu LWu CWang GYu HJiang YGui MXia NChen YSun HChen TXi XTian KChen KYuan QZheng QZeng YYang CXin JLi YYang YHuang YLi SLiu CHuo NLin LfalseA broadly neutralizing antibody confers cross-genus protection against alphaherpesviruses by inhibiting gB-mediated membrane fusion.The global prevalence and disease burden of alphaherpesviruses infections, including human-infecting viruses such as HSV-1, HSV-2, and VZV, as well as animal-infecting viruses like PRV, BHV, CHV, and FHV, highlight the unmet need for more effective and universal antiviral strategies. However, there has been no significant progress in developing broad-spectrum interventions against herpesvirus. Here we report the identification of a broadly neutralizing antibody against alphaherpesviruses, 16F9, which targets the glycoprotein B (gB) of alphaherpesviruses and offers cross-protection against multiple viruses such as HSV-1, HSV-2, and PRV in mice. 16F9 demonstrated robust therapeutic efficacy in various female mouse models of herpesvirus diseases including PRV-induced viral encephalitis, HSV-12025-01-01T00:00:00Z2025 Dec2026-06-06T04:13:11.592Z2026-05-25T03:12:03.917ZS-EPMC127086804140225110.1038/s41467-025-66099-8