摘要Herpes simplex virus type 1(HSV-1)causes lifelong latent infection and is associated with severe diseases,including herpes simplex encephalitis,neonatal herpes,and no licensed vaccine is currently available for this pathogen.Here,we systematically evaluated an attenuated HSV-1 platform with deletions in ICP34.5 and ICP47 genes(HSV-1 △34.5△47)for application as a dual-function vaccine.This construct,generated by BAC-galK recombination,showed attenuated replication in vitro.Notably,it elicited robust humoral and cellular immune responses in mice,and provided complete protection against lethal challenge with virulent HSV-1 McKrae strain through both corneal and genital tract infection routes.To assess its utility for heterologous antigen delivery,we engineered a recombinant HSV-1 △34.5△47-N,which expresses the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)nucleocapsid(N)protein.This recombinant virus retained the protective efficacy against HSV-1 and induced robust N-specific immune responses.Passive serum transfer and in vivo T-cell depletion studies demonstrated that humoral immunity was sufficient to mediate protective immunity against HSV-1 challenge.Safety assessment revealed no detectable viral mRNA or patho-logical lesions in the brains of immunized animals.These findings support HSV-1 △34.5△47 as a safe and versatile platform for both HSV-1 prophylaxis and heterologous antigen delivery.