Multiplexing mRNAs builds a "broad-immunity wall" against the flu

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Influenza viruses pose a significant global health threat.
• Current influenza vaccines offer strain-specific protection, requiring annual updates.
• Developing broadly protective influenza vaccines remains a critical unmet need.

Purpose of the Study:

• To evaluate the immunogenicity and protective efficacy of messenger RNA (mRNA) vaccines encoding diverse influenza hemagglutinin (HA) antigens.
• To assess the potential of a universal influenza vaccine strategy.

Main Methods:

• Construction and delivery of mRNA encoding HA antigens from all known influenza subtypes and lineages.
• Immunization of animal models with the candidate mRNA vaccines.
• Assessment of antibody responses, including cross-reactivity against various influenza strains.
• Evaluation of protection against homologous and heterologous influenza virus challenge.

Main Results:

• Delivery of mRNAs encoding influenza HA antigens elicited robust and cross-reactive antibody responses.
• Vaccination conferred significant protection against homologous and heterologous influenza virus challenge.
• The breadth of HA subtypes included in the mRNA vaccine formulation was critical for broad immunity.

Conclusions:

• mRNA vaccines encoding a comprehensive set of influenza HA antigens can induce cross-reactive and protective immunity.
• This mRNA-based approach represents a promising platform for developing a universal influenza vaccine.
• Further development of this strategy could revolutionize influenza prevention efforts.