Mucosal vaccination against SARS-CoV-2 using recombinant influenza viruses delivering self-assembling nanoparticles
Devaki Pilapitiya1, Wen Shi Lee1, Mai N Vu1
1Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.
Recombinant influenza viruses carrying SARS-CoV-2 RBD genes effectively induce mucosal and systemic immunity. Ferritin nanoparticle vaccines show superior antibody responses and enhance lung immunity, offering a promising strategy for respiratory infections.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Recombinant influenza viruses are effective mucosal vaccine vectors.
- SARS-CoV-2 spike protein receptor-binding domain (RBD) is a key target for vaccines.
- Mucosal immunity is crucial for preventing respiratory viral infections.
Purpose of the Study:
- To evaluate recombinant influenza viruses expressing SARS-CoV-2 RBD genes.
- To compare immune responses elicited by monomeric, trimeric, and nanoparticle RBD forms.
- To assess the potential for augmenting mucosal and systemic immunity against SARS-CoV-2.
Main Methods:
- Generation of replication-competent recombinant influenza viruses with SARS-CoV-2 RBD genes (monomeric, trimeric, ferritin nanoparticles) using reverse genetics.
- Intranasal and intramuscular immunisation of mice.
- Assessment of serological and mucosal antibody responses (IgG, IgA).
- Analysis of lung-resident memory B cells and germinal center B cells.
- Evaluation of neutralising antibody titres and immune cell recall responses.
Main Results:
- Intranasal immunisation induced potent anti-RBD antibody responses, with ferritin nanoparticles outperforming monomeric and trimeric forms.
- Both parenteral and mucosal immunisation generated robust serum anti-RBD IgG.
- Mucosal immunisation specifically induced respiratory IgA, and RBD-specific lung-resident memory and germinal center B cells.
- Intranasal boosting in previously vaccinated animals enhanced mucosal immunity and lung neutralising titres.
- Antigen re-exposure in the lung promoted antibody-secreting cell recall and maintained lung germinal centers.
Conclusions:
- Recombinant influenza viruses effectively deliver immunogenic self-assembling nanoparticles.
- This strategy generates robust antibody and B cell responses in the respiratory mucosa.
- The approach offers a viable method to enhance lung-localised immunity against respiratory viruses.
- Ferritin nanoparticle-based vaccines show promise for improving mucosal vaccine efficacy.
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