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A novel Orf virus (ORFV)-based spike vaccine (ORFV-S) combined with a protein vaccine enhances immune responses against viral variants. This heterologous prime-boost strategy improves antibody breadth and T-cell activity for broader protection.

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Orf VirusSARS-CoV-2VidPrevtyn Betaheterologous prime-boostvaccinesviral vector

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Area of Science:

  • Virology
  • Immunology
  • Vaccinology

Background:

  • Emerging immune-evasive viral variants necessitate vaccines offering broad and durable protection.
  • Heterologous prime-boost regimens using diverse vaccine platforms can improve immune responses.

Purpose of the Study:

  • To evaluate a heterologous prime-boost strategy combining an Orf virus (Parapoxvirus orf, ORFV)-based spike vaccine (ORFV-S) with a licensed protein vaccine.
  • To assess the impact on humoral and cellular immunity against viral variants.

Main Methods:

  • Mice received intramuscular homologous or heterologous prime-boost regimens with ORFV-S and VidPrevtyn Beta.
  • Spike-specific humoral (IgG) and cellular (T-cell) immune responses were analyzed.

Main Results:

  • ORFV-S alone generated potent, broad IgG responses and strong ACE2-binding inhibition across variants.
  • Heterologous ORFV-S priming followed by protein boosting significantly increased antibody magnitude and cross-variant breadth compared to protein-only vaccination.
  • ORFV-S, in both homologous and heterologous settings, induced robust CD4+ and CD8+ T-cell responses, unlike protein vaccine alone.

Conclusions:

  • The ORFV-S vaccine vector is effective in eliciting broad humoral and cellular immunity.
  • Heterologous prime-boost combinations with ORFV-S enhance immune responses beyond homologous protein vaccination.
  • This strategy supports vaccine development against evolving viral pathogens.