Inhaled booster vaccination with an MVA-based SARS-CoV-2 vaccine candidate induces T cell responses in lung

  1. Swantje I. Hammerschmidt
  2. Rodrigo Gutierrez Jauregui
  3. Joana Barros-Martins
  4. Ivan Odak
  5. Lennart Riemann
  6. Verena Krähling
  7. Anika Buchholz
  8. Mahnaz Badpa
  9. Georgia Kalodimou
  10. Alina Tscherne
  11. Michaela Friedrichsen
  12. Inga Ravens
  13. Jasmin Ristenpart
  14. Anja Schimrock
  15. Larissa Kasperek
  16. Simon Schröder
  17. Antonia Zapf
  18. Christine Falk
  19. Stephan Becker
  20. Gerd Sutter
  21. Asisa Volz
  22. Christoph Schindler
  23. Jens M. Hohlfeld
  24. Reinhold Förster
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Abstract

Background

Parenteral COVID-19 vaccines induce strong systemic immunity, but they do not typically trigger pronounced respiratory immunity. In this context, mucosally applied vaccines might help to induce local immune responses for early viral clearance and reduced viral transmission.

Methods

In this investigator-initiated, open-label single-dose phase I trial, we analyzed the immunogenicity and safety of the vaccine candidate MVA-SARS-2-ST administered as an inhalation boost in COVID-19-immunized adults (n=23). MVA-SARS-2-ST represents a replication-deficient vector vaccine candidate built on the recombinant Modified Vaccinia virus Ankara (MVA) platform and expresses a prefusion-stabilized version of the full-length spike glycoprotein of SARS-CoV-2.

Results

While there was no increase in spike-specific antibodies in the blood, the inhalation of 10 7 infectious units (IU) MVA-SARS-2-ST led to an increase in IFN-γ release after re-stimulation of whole blood with spike peptides. This enhanced IFN-γ release peaked at day 7 and remained detectable for at least 140 days after vaccination. Notably, selectively individuals with a history of COVID-19 (nucleocapsid protein (NCP)-seropositive study participants), but not individuals without a history of COVID-19 (NCP-seronegative study participants), showed a trend towards increased spike-specific IgA in the lung after inhalation of 10 7 IU MVA-SARS-2-ST. In contrast, inhaled application of MVA-SARS-2-ST robustly induced spike-specific CD4+ and CD8+ T cell responses in the lung in both NCP-seronegative and NCP-seropositive individuals.

Conclusions

Collectively, our study demonstrated that a single booster inhalation of 10 7 IU MVA-SARS-2-ST did not have a relevant impact on the humoral immune response, but induced specific T cell responses in blood and lung.

Article activity feed

  1. Version published to 10.1101/2025.10.09.25337642 on medRxiv