A replication-incompetent adenoviral vector encoding for HSV-2 gD2 is immunogenic and protective against HSV-2 intravaginal challenge in mice

PLoS One. 2024 Dec 31;19(12):e0310250. doi: 10.1371/journal.pone.0310250. eCollection 2024.

Abstract

Herpes Simplex virus (HSV) is the cause of genital herpes and no prophylactic treatment is currently available. Replication-incompetent adenoviral vectors are potent inducers of humoral and cellular immune responses in humans. We have designed an adenoviral vector type 35 (Ad35)-based vaccine encoding the HSV-2 major surface antigen gD2 (Ad35.HSV.gD2). Immunization of mice with Ad35.HSV.gD2 elicited virus neutralizing antibody titers (VNT) and cellular responses against HSV-2 and HSV-1. While immunity was lower than for CJ2-gD2, both vaccines showed 100% survival against intravaginal challenge with HSV-2 G strain and a strong inverse correlation was observed between HSV-2 infection (as measured by viral shedding) and VNT. A combination of Ad35.HSV.gD2 with Ad35 encoding for gB2 (Ad35.HSV.gB2) resulted in increased VNT and lower infection, compared with Ad35.HSV.gD2 alone. Transfer of immune serum into naïve BALB/c mice before intravaginal challenge confirmed the role of antibodies in the protection of mice against infection although other immune factors may play a role as well.

MeSH terms

  • Adenoviridae* / genetics
  • Adenoviridae* / immunology
  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Female
  • Genetic Vectors* / genetics
  • Genetic Vectors* / immunology
  • Herpes Genitalis* / immunology
  • Herpes Genitalis* / prevention & control
  • Herpesvirus 2, Human* / genetics
  • Herpesvirus 2, Human* / immunology
  • Humans
  • Mice
  • Mice, Inbred BALB C*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology
  • Virus Replication

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Viral Envelope Proteins
  • glycoprotein D-herpes simplex virus type 2

Grants and funding

E.R. was funded by the European Union’s Horizon 2020 Research and Innovation Program (H2020) under the Marie Skłodowska-Curie Innovative Training Networks Programme MSCA-ITN GA 675278 EDGE (Training Network providing cutting-EDGE knowlEDGE on Herpes Virology and Immunology). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.