Oral Presentation ANZBMS-MEPSA-ANZORS 2022

Mucosal protein-based vaccination with a TLR2-stimulating adjuvant induces potent local immunity against SARS-CoV-2 in mice (#84)

Anneliese s Ashhurst 1 2 3 , Matt D Johansen 4 , Joshua WC Maxwell 1 5 , Caroline L Ashley 3 , Anupriya Aggarwal 6 , Rezwan Siddiquee 7 8 , Joel P Mackay 7 , Claudio Counoupas 2 3 , Scott N Byrne 3 , Stuart Turville 6 , Megan Steain 3 , Jamie A Triccas 3 , Philip M Hansbro 4 , Richard J Payne 1 5 , Warwick J Britton 2 9
  1. School of Chemistry, University of Sydney, Sydney, NSW, Australia
  2. Tuberculosis Research Program, Centenary Institute, Sydney, NSW, Australia
  3. Infection, Immunity and Inflammation Theme, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia
  4. Centre for Inflammation, Centenary Institute and Faculty of Science, School of Life Sciences, University of Technology, Sydney, NSW, Australia
  5. Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, University of Sydney, Sydney, New South Wales, Australia
  6. Kirby Institute, Sydney, NSW, Australia
  7. School of Life and Environmental Sciences, The University of Sydney, Sydney, NSW, Australia
  8. Sydney Analytical, The University of Sydney, Sydney, NSW, Australia
  9. Department of Clinical Immunology, Royal Prince Alfred Hospital, Sydney, NSW, Australia

The development of vaccines against SARS-CoV-2 has provided critical opportunities to reduce the morbidity and mortality associated with COVID-19. While current vaccines can reduce the risk of transmission, enhancing mucosal immunity to provide a barrier against infection may further increase protection, and importantly, minimise viral spread. Mucosal vaccination, including protein-based vaccines with the inclusion of appropriate adjuvants, have proven advantageous in vaccine studies for multiple respiratory pathogens. We tested a novel subunit vaccine, consisting of SARS-CoV-2 Spike protein with a TLR2-stimulating adjuvant, delivered peripherally (sub-cutaneously) or mucosally (intra-nasally) to mice. Vaccination by either route led to substantial serum anti-Spike IgG titres, and high neutralising titres when tested against a lentivirus expressing SARS-CoV-2 Spike, or SARS-CoV-2 virus. Importantly, mucosal vaccination generated anti-Spike IgA, as well as increased neutralising antibodies in both the serum and airways. Additionally, mucosal vaccination facilitated increased lung Spike-specific CD4+ T-cell responses. In the pulmonary environment, TLR2 is expressed by both respiratory epithelia and immune cells. Using TLR2 deficient chimeric mice, we determined that TLR2 expression in either compartment facilitated early innate responses to mucosal vaccination. By contrast, TLR2 on hematopoietic cells was essential for optimal lung-localised, antigen-specific responses. In K18-hACE2 mice, vaccination provided complete protection against disease and sterilising lung immunity against SARS-CoV-2 challenge. Mucosal vaccines may therefore provide a powerful strategy to generate local protective responses against SARS-CoV-2 and other respiratory viruses, with potential to reduce risk of infection and transmission.