Evaluation of an H5 influenza virus mRNA-lipid nanoparticle (LNP) vaccine in lactating dairy cows

Abstract Highly pathogenic avian influenza (HPAI) clade 2.3.4.4b H5N1 virus has recently emerged in dairy cattle in the United States. The virus replicates primarily in the mammary gland of infected cattle, leading to dramatic reductions in milk production. It is thought that the virus transmits from animal to animal through viral shedding in milk, and therefore, vaccines that decrease the amount of virus in milk can potentially limit the current outbreak and reduce the risk of H5N1 spillover into humans. Here, we assess the immunogenicity and efficacy of a clade 2.3.4.4b H5 mRNA-LNP vaccine in lactating dairy cows. We found that the H5 mRNA-LNP vaccine elicited robust antibody responses in sera and milk and significantly reduced viral replication and disease caused by clade 2.3.4.4b H5N1 intramammary infection. Competing Interest Statement S.E.H. and D.W. are co-inventors on patents that describe the use of nucleoside-modified mRNA as a platform to deliver therapeutic proteins and as a vaccine platform. D.W. is also named on patents describing the use of lipid nanoparticles and lipid compositions for nucleic acid delivery. S.E.H. reports receiving consulting fees from Sanofi, Pfizer, Lumen, Novavax, and Merck. JDB consults for Apriori Bio, Invivyd, GSK, Pfizer, and the Vaccine Company. JDB and BD are inventors on Fred Hutch licensed patents related to viral deep mutational scanning.