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Intranasally Inoculated SARS-CoV-2 Spike Protein Combined with Mucoadhesive Polymer Induces Broad and Long-Lasting
Tomoko Honda1, Sakiko Toyama1,2, Yusuke Matsumoto1
1Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
Vaccines
|July 27, 2024
Summary
An intranasal SARS-CoV-2 vaccine using spike protein and carboxy-vinyl polymer (S-CVP) effectively induced mucosal immunity and long-lasting protection against variants. This S-CVP vaccine offers a promising alternative to current mRNA vaccines.
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- Current mRNA vaccines against SARS-CoV-2 induce systemic immunity but lack mucosal immunity, a key factor in preventing respiratory infections.
- The protective efficacy of existing vaccines wanes over time, necessitating strategies for sustained immunity.
- Intranasal vaccines offer a non-invasive approach with the potential to activate crucial mucosal immunity.
Purpose of the Study:
- To evaluate the effectiveness of an intranasally administered SARS-CoV-2 spike protein formulated with carboxy-vinyl polymer (S-CVP).
- To compare the immunogenicity and protective efficacy of S-CVP with a traditional aluminum potassium sulfate adjuvant.
- To assess the durability of immune responses and protection against diverse SARS-CoV-2 variants.
Main Methods:
- Mice were intranasally inoculated with S-CVP or spike protein with aluminum potassium sulfate.
- Humoral (IgG, IgA, neutralizing antibodies) and cellular immunity were measured.
- Mice were challenged with SARS-CoV-2 strains (early and Omicron variants).
- Viral load, lung inflammation, and survival were assessed.
Main Results:
- Intranasal S-CVP strongly induced antigen-specific IgG, neutralizing antibodies, and cellular immunity, surpassing the aluminum potassium sulfate adjuvant.
- S-CVP vaccination uniquely elicited IgA production, indicating mucosal immune activation.
- S-CVP conferred significant protection against SARS-CoV-2 challenge, reducing viral load and lung inflammation, dependent on CD8+ T cells and myeloid cells.
- Robust antibody responses and protection against Omicron BA.5 persisted for over 15 months post-immunization.
Conclusions:
- Intranasal S-CVP vaccination is a highly effective strategy for inducing both systemic and mucosal immunity against SARS-CoV-2.
- The S-CVP vaccine demonstrates superior immunogenicity and durability compared to traditional adjuvants.
- S-CVP offers a promising platform for developing long-lasting vaccines against SARS-CoV-2 and its variants.
