2. Academic Validation
  3. Systematic evaluation of HSV-1 Δ34.5Δ47 as a dual-function platform for attenuated HSV-1 vaccine and heterologous antigen delivery

Systematic evaluation of HSV-1 Δ34.5Δ47 as a dual-function platform for attenuated HSV-1 vaccine and heterologous antigen delivery

  • Virol Sin. 2026 Jan 23:S1995-820X(26)00008-8. doi: 10.1016/j.virs.2026.01.002.
Ziyu Wen 1,  Haohang Wang 1,  Yu Liao 1,  Shunran Li 1,  Minjuan Shi 1,  Mingting Cui 1,  Jun Qian 2,  Caijun Sun 3
Affiliations

Affiliations

  • 1 School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China.
  • 2 School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China; Shenzhen Key Laboratory of Pathogenic Microbes and Biosafety, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China; State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, China.
  • 3 School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China; Shenzhen Key Laboratory of Pathogenic Microbes and Biosafety, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China; State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, China. Electronic address: [email protected].
PMID: 41581759 DOI: 10.1016/j.virs.2026.01.002
Abstract

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 Δ34.5Δ47) 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 Δ34.5Δ47-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 pathological lesions in the brains of immunized Animals. These findings support HSV-1 Δ34.5Δ47 as a safe and versatile platform for both HSV-1 prophylaxis and heterologous antigen delivery.

Keywords

Attenuated vaccine; Herpes simplex virus type 1 (HSV-1); Humoral immunity; SARS-CoV-2; Viral vector.

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