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

A delta-inulin adjuvanted SARS-CoV-2 vaccine generates a robust lung-resident cellular and humoral immune response when delivered intratracheally (#121)

Erica Stewart 1 , Claudio Counoupas 1 2 , Kia Ferrell 1 , Anneliese Ashhurst 1 2 , Megan Steain 1 , Caroline Ashley 1 , Warwick Britton 2 3 , Nikolai Petrovsky 4 5 , Jamie Triccas 1 6
  1. School of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia
  2. Tuberculosis Research Program, Centenary Institute, Sydney, NSW, Australia
  3. Department of Clinical Immunology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
  4. Vaxine Pty Ltd, Adelaide, South Australia, Australia
  5. College of Medicine and Health, Flinders University, Adelaide, South Australia, Australia
  6. Marie Bashir Institute for Infectious Diseases and Biosecurity, Sydney, NSW, Australia

Several SARS-CoV-2 vaccine candidates have progressed through clinical trials in record time since the beginning of the global Covid-19 pandemic. However, there remains a significant need for vaccines that are safe, affordable, and amenable to transport to rural areas. Mucosal vaccination is favored for its capacity to induce immune memory targeted to the site of infection, making it appealing for SARS-CoV-2 vaccine strategies. In this study we performed in-depth analysis of the immune responses generated by a subunit recombinant spike protein vaccine containing the delta-inulin adjuvant Advax when administered intratracheally versus intramuscularly. We performed multi-colour flow cytometric analysis on circulating antigen-specific T cell responses and lung-resident memory responses eight weeks after booster vaccination and characterized plasma and broncho-alveolar lavage fluid antibody responses. While both methods produced robust neutralizing antibody responses, intratracheal delivery generated significantly higher systemic and lung-localized neutralizing antibody titers. Inducible bronchus-associated lymphoid tissue, a site of lymphocyte antigen presentation and proliferation, was visible in the lungs of intratracheally vaccinated mice. This was coupled with robust and long-lasting lung tissue-resident memory CD4+ and CD8+ T cells, as well as circulating memory CD4+ T cell memory that was not present in intramuscularly vaccinated mice. The cellular response in the lungs and bronchoalveolar lavage fluid primarily consisted of Th17 cells expressing IL-17A, with some Th2 cells. There were also higher numbers of CD8+ T cells with a tissue resident memory phenotype in intratracheally vaccinated animals. This study provides a detailed view of the lung-resident cellular response to intratracheal vaccination and demonstrates the importance of delivery site selection in the development of SARS-CoV-2 vaccine candidates. These data provide pre-clinical evidence to support the progression of SARS-CoV-2 vaccine candidates containing delta-inulin adjuvants to clinical trials.