Induction of Superior Systemic and Mucosal Protective Immunity to SARS-CoV-2 by Nasal Administration of a VSV–ΔG–Spike Vaccine

Yfat Yahalom-Ronen, Sharon Melamed, Boaz Politi, Noam Erez, Hadas Tamir, Liat Bar-On, Julia Ryvkin, Dena Leshkowitz, Ofir Israeli, Shay Weiss, Amir Ben-Shmuel, Moria Barlev-Gross, Lilach Cherry Mimran, Hagit Achdout, Nir Paran, Tomer Israely

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


The emergence of rapidly spreading variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) poses a major challenge to vaccines’ protective efficacy. Intramuscular (IM) vaccine administration induces short-lived immunity but does not prevent infection and transmission. New vaccination strategies are needed to extend the longevity of vaccine protection, induce mucosal and systemic immunity and prevent viral transmission. The intranasal (IN) administration of the VSV–ΔG–spike vaccine candidate directly to mucosal surfaces yielded superior mucosal and systemic immunity at lower vaccine doses. Compared to IM vaccination in the K18–hACE2 model, IN vaccination preferentially induced mucosal IgA and T-cells, reduced the viral load at the site of infection, and ameliorated disease-associated brain gene expression. IN vaccination was protective even one year after administration. As most of the world population has been vaccinated by IM injection, we demonstrate the potential of a heterologous IM + IN vaccination regimen to induce mucosal immunity while maintaining systemic immunity. Furthermore, the IM + IN regimen prevented virus transmission in a golden Syrian hamster co-caging model. Taken together, we show that IN vaccination with VSV–ΔG–spike, either as a homologous IN + IN regimen or as a boost following IM vaccination, has a favorable potential over IM vaccination in inducing efficient mucosal immunity, long-term protection and preventing virus transmission.

Original languageEnglish
Article number491
Issue number5
StatePublished - 1 May 2024
Externally publishedYes

Bibliographical note

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© 2024 by the authors.


  • SARS-CoV-2
  • VSV–∆G–spike
  • immunity
  • mucosal vaccination
  • nasal vaccination
  • vaccine


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