ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

Mucosal protein-based vaccination with a TLR2-stimulating adjuvant induces potent local immunity against SARS-CoV-2 in mice (#160)

Anneliese S Ashhurst 1 2 3 , Matt D Johansen 4 , Joshua WC Maxwell 2 5 , Caroline L Ashley 3 , Anupriya Aggarwal 6 , Rezwan Siddiquee 7 8 , Joel P Mackay 7 , Claudio Counoupas 1 3 , Scott N Byrne 3 , Stuart Turville 6 , Megan Steain 3 , James A Triccas 3 , Philip M Hansbro 4 , Richard J Payne 2 5 , Warwick J Britton 1 9
  1. Tuberculosis Research Program, Centenary Institute, Sydney, NSW, Australia
  2. School of Chemistry, University of Sydney, 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. To establish the contribution of these compartments to the mucosal vaccine response, we performed WT or TLR2KO bone marrow transfer into irradiated WT or TLR2KO mice. Mice deficient in TLR2 on both the epithelia and hematopoietic compartments had very minimal responses to mucosal vaccination, indicating that vaccine-induced immune activation was dependent on TLR2 stimulation. Interestingly, induction of early innate responses in the lungs and airways, in particular neutrophil influx, was facilitated by TLR2 expression on either the epithelia or immune cells. However, expression of TLR2 on the hematopoietic compartment was required for optimal generation of lung localised antigen-specific adaptive responses. Mucosal vaccines may therefore provide a powerful strategy to generate local protective responses against SARS-CoV-2, with potential to reduce risk of infection and transmission. Protection studies to compare routes of vaccination are ongoing in a K18-hACE2 murine model of SARS-CoV-2 infection.