Key Findings
The H5 mRNA-LNP vaccine demonstrated high efficacy in protecting lactating dairy cows against intramammary infection of the highly pathogenic avian influenza (HPAI) clade 2.3.4.4b H5N1 virus. Following a viral challenge, vaccinated cows exhibited approximately 1,000-fold lower peak viral RNA in their milk compared to the control group. Additionally, vaccination resulted in a lower occurrence of mammary fibrosis and clinical mastitis.
Technical Details
The vaccine encodes the hemagglutinin (HA) of A/dairy cattle/Texas/24-008749-002/2024, a strain representative of bovine H5N1 viruses currently circulating in the USA. The study involved eight Holstein dairy cows aged 2 to 8 years, divided into vaccinated and control groups. The vaccination protocol consisted of two intramuscular doses of 500 μg of H5 mRNA-LNP administered 3 weeks apart. Control animals received saline injections.
Immunogenicity assessments revealed that the vaccine elicited HA-reactive and neutralizing antibodies in the serum, as well as HA-reactive antibodies in the milk. The animals were challenged via intramammary inoculation 49 days after the initial dose.
Background & Context
HPAI clade 2.3.4.4b H5N1 has emerged in cattle across 19 US states, causing severe mastitis and sharp reductions in milk production. Unlike typical influenza, the primary site of viral replication in lactating cattle is the mammary tissue rather than the respiratory tract. Viral transmission between animals is believed to occur through shedding in milk. The virus exhibits tropism for alveolar milk-secreting epithelial cells and the interlobular space of the mammary gland.
Significance & Outlook
The ability of the mRNA-LNP vaccine to induce antibodies in both serum and milk addresses the specific pathology of bovine H5N1. By limiting viral replication in the mammary glands, this technology may reduce the dramatic drop in milk production and economic losses in the dairy sector. Furthermore, reducing viral shedding in cattle may lower the risk of mammalian adaptation and potential human-to-human transmission.
Source: https://doi.org/10.1038/s41587-026-03343-6
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