Universal influenza A vaccine: optimization of M2-based constructs

Area of Science:

• Virology
• Immunology
• Vaccine Development

Background:

• The M2e peptide of influenza A is poorly immunogenic, contributing to its conserved sequence across strains.
• Linking M2e to carriers like hepatitis B core (HBc) particles enhances its immunogenicity and protective capacity.

Purpose of the Study:

• To compare different M2e-HBc vaccine formulations and administration routes for optimal induction of protective immunity against influenza A.
• To evaluate the immunogenicity and protective efficacy of optimized M2e-HBc constructs.

Main Methods:

• Construction and characterization of various M2e-HBc particles with different M2e copy numbers and linkage strategies.
• Assessment of immunogenicity through antibody titer measurements (anti-M2e and anti-HBc).
• Evaluation of protective efficacy in mouse models challenged with a lethal influenza A virus dose.

Main Results:

• Both intraperitoneal and intranasal administration of M2e-HBc vaccines induced strong immunogenicity and full protection in mice.
• A construct with three consecutive M2e copies linked to the N-terminus of HBc showed the highest protective efficacy.
• The optimized M2e-HBc vaccine elicited anti-M2e antibody titers exceeding those against HBc.

Conclusions:

• Optimized M2e-HBc vaccines are highly immunogenic and capable of conferring complete protection against lethal influenza A challenge in mice.
• The M2e-HBc platform represents a promising vaccine strategy for influenza A, with potential for human application.
• Further development of M2e-HBc vaccines could lead to effective cross-protective influenza A vaccines.