Highly immunogenic influenza virus-like particles containing B-cell-activating factor (BAFF) for multi-subtype...

Area of Science:

• Vaccinology
• Immunology
• Biotechnology

Background:

• Virus-like particle (VLP) technology offers a promising platform for developing influenza vaccines.
• Influenza VLPs are produced by overexpressing viral proteins (HA, M1, NA, M2) in various cell systems.
• Enhancing VLP immunogenicity is crucial for effective vaccine development.

Purpose of the Study:

• To engineer highly immunogenic influenza VLPs by molecularly incorporating B-cell-activating factor (BAFF) or proliferation-inducing ligand (APRIL).
• To evaluate the immunogenicity and protective efficacy of these modified VLPs against H5N1 influenza.
• To explore the potential of multi-subtype BAFF-VLPs for broader influenza protection.

Main Methods:

• Influenza VLPs were engineered by fusing BAFF or APRIL to the transmembrane-anchored domain of the H5 hemagglutinin (HA) gene.
• Immunizations were performed using these modified VLPs formulated with either alum or MPL adjuvant.
• Humoral immune responses (IgG titers, neutralizing antibodies) and protection against live virus challenge were assessed.

Main Results:

• Influenza VLPs incorporating BAFF or APRIL, formulated with alum adjuvant, induced significantly higher IgG titers compared to MPL adjuvant.
• BAFF-VLPs formulated with alum elicited broadly neutralizing antibodies against homologous and heterologous H5N1 strains, conferring protection.
• Multi-subtype H5H7 and H1H5H7 BAFF-VLPs induced neutralizing antibodies against multiple HA subtypes.

Conclusions:

• Molecular incorporation of BAFF or APRIL enhances the immunogenicity of influenza VLPs.
• Alum adjuvant is superior to MPL for eliciting protective immune responses with these engineered VLPs.
• Multi-subtype BAFF-VLPs represent a viable strategy for developing broadly protective influenza vaccines.