Inducing potent and protective immunity against SARS-CoV-2 with intranasally administered lipopeptide vaccines targeting TLR-2 — ASN Events
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  2. SESSION 12: Inflammation, immunity and infection
  3. Inducing potent and protective immunity against SARS-CoV-2 with intranasally administered lipopeptide vaccines targeting TLR-2

Inducing potent and protective immunity against SARS-CoV-2 with intranasally administered lipopeptide vaccines targeting TLR-2 (#65)

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

The development and widespread administration of vaccines targeting SARS-CoV-2 proved to be the pivotal therapeutic intervention in combatting the COVID-19 pandemic. While highly successful in reducing mortality and morbidity, novel vaccination strategies are needed to withstand the persistent outbreaks associated with the continual evolution of the SARS-CoV-2 virus. One exciting avenue of exploration is a mucosal vaccination strategy to induce local immunity in the respiratory passage, which has demonstrable benefit in combating respiratory pathogens. To this end, we sought to explore the utility of novel subunit vaccines, consisting of SARS-CoV-2 Spike antigens in combination with a TLR2-stimulating lipopeptide adjuvant, Pam2Cys, delivered peripherally (sub-cutaneously) or mucosally (intra-nasally) to mice. We first explored the possibility of neutralising the virus using self-adjuvanting peptide vaccines composed of Pam2Cys conjugated to various epitopes derived from the mature sequence of the spike protein. While a number of these peptide vaccines induced robust T-cell responses and high titres of antibodies against the spike protein, they failed to provide significant protection against viral entry in vitro. In stark contrast, a subunit vaccine composed of Pam2Cys admixed with recombinant spike protein led to substantial circulating anti-Spike IgG and high neutralising titres against SARS-CoV-2 virus. Of note, mucosal vaccination of this subunit vaccine increased neutralising antibodies in the serum, airways, and nasal passages and provided complete protection from Delta SARS-CoV-2 infectious challenge in a K18-hACE2 mouse model.

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