Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus

Area of Science:

• Virology
• Vaccinology
• Immunology

Background:

• Highly pathogenic avian influenza viruses (HPAI) of the H5 clade 2.3.4.4b pose a significant pandemic threat due to widespread circulation in avian populations and potential for human adaptation.
• Traditional vaccine development relies on egg-based systems, which can be time-consuming and may not be suitable for rapidly emerging viral strains.
• Messenger RNA (mRNA) lipid nanoparticle (LNP) vaccine technology offers a potential solution for rapid vaccine production during pandemics.

Purpose of the Study:

• To develop and evaluate an mRNA-LNP vaccine encoding the hemagglutinin (HA) glycoprotein from a circulating H5 clade 2.3.4.4b avian influenza virus.
• To assess the immunogenicity and protective efficacy of the H5 mRNA-LNP vaccine in preclinical animal models.

Main Methods:

• Generation of a monovalent mRNA-LNP vaccine encoding the HA glycoprotein of an H5 clade 2.3.4.4b isolate.
• Evaluation of vaccine immunogenicity in female mice, measuring T cell and antibody responses, including neutralizing and broadly-reactive anti-HA stalk antibodies.
• Comparison of antibody responses to whole inactivated virus vaccines in mice with and without prior H1N1 exposure.
• Assessment of vaccine efficacy in male ferrets, including challenge with H5N1 virus to evaluate protection against morbidity and mortality.

Main Results:

• The H5 mRNA-LNP vaccine successfully elicited robust T cell and antibody responses in female mice.
• Neutralizing antibodies and broadly-reactive anti-HA stalk antibodies were detected in vaccinated mice.
• Antibody levels in mice vaccinated with H5 mRNA-LNP were comparable to those vaccinated with whole inactivated vaccines.
• The H5 mRNA-LNP vaccine was found to be immunogenic in male ferrets and provided significant protection against morbidity and mortality following H5N1 challenge.

Conclusions:

• A monovalent mRNA-LNP vaccine encoding the H5 clade 2.3.4.4b hemagglutinin is immunogenic and protective in preclinical models.
• This mRNA-LNP vaccine platform demonstrates potential for rapid development and deployment against emerging avian influenza threats.
• The findings support the continued development of mRNA-LNP vaccines for pandemic influenza preparedness.