ISCOMs/MPLA-Adjuvanted SDAD Protein Nanoparticles Induce Improved Mucosal Immune Responses and Cross-Protection in...

Area of Science:

• Immunology
• Vaccinology
• Nanotechnology

Background:

• Influenza virus epidemics pose significant public health and economic threats.
• Developing effective mucosal vaccines and adjuvants is crucial for combating respiratory infections at their entry point.
• Improving immunogenicity of influenza vaccines is a key strategy for enhanced protection.

Purpose of the Study:

• To develop and evaluate novel core/shell protein nanoparticles as potential influenza vaccines.
• To investigate the adjuvant effects of Immune-stimulating complexes (ISCOMs)/monophosphoryl lipid A (MPLA) on nanoparticle immunogenicity.
• To assess the efficacy of intranasally delivered nanoparticles as mucosal vaccines against influenza.

Main Methods:

• Core/shell protein nanoparticles were constructed using influenza nucleoprotein (NP) core and NA1-M2e or NA2-M2e fusion proteins via SDAD crosslinking.
• ISCOMs/MPLA adjuvants were used to enhance immune responses induced by NP/NA-M2e SDAD protein nanoparticles.
• Nanoparticles were administered intramuscularly and intranasally in mice to evaluate systemic and mucosal immunity.
• Immune responses, including antibody titers, cytokine production, and T/B cell populations, were analyzed post-challenge with H3N2 influenza viruses.

Main Results:

• ISCOMs/MPLA-adjuvanted nanoparticles significantly boosted antigen-specific antibody responses and cytokine-secreting splenocytes.
• Intranasal administration induced higher levels of antigen-specific IgA and IgG in the local mucosa.
• Significant expansion of lung-resident memory T and B cells (T_RM /B_RM ) and alveolar macrophages was observed.
• Mice immunized with ISCOMs/MPLA-adjuvanted nanoparticles showed 100% survival against homologous and heterologous H3N2 viral challenges.

Conclusions:

• ISCOMs/MPLA-adjuvanted protein nanoparticles represent a promising strategy for developing effective influenza vaccines.
• This novel vaccine platform can induce strong systemic and mucosal immune responses, conferring protection regardless of immunization route.
• The developed nanoparticles demonstrate potential for broad protection against influenza, including heterologous strains.