Location: Virus and Prion Research
Project Number: 5030-32000-231-113-R
Project Type: Reimbursable Cooperative Agreement
Start Date: Aug 1, 2024
End Date: Jul 31, 2025
Objective:
The objectives are to investigate the pathogenesis, vaccine efficacy and apparent seroprevalence of highly pathogenic avian influenza A (H5N1) clade 2.3.4.4b strain in cattle. New information indicates Holstein cattle can be infected with HPAI resulting in disease and onward transmission and may act as an intermediate host for human influenza pandemics (1). The epidemiology, route of infection, and tissue tropism of HPAI in cattle is unknown as the situation is emerging. It is important to understand the consequences of HPAI infection in cattle as a risk to cattle health and to assess the potential risk to humans. To gain this understanding it is vital to conduct animal studies requiring the direct inoculation of cows and calves with HPAI.
Approach:
Aim 1. Evaluate the susceptibility to and pathogenesis of HPAI H5N1 2.3.4.4b in cattle.
Sub-aim 1.1. Complete pathogenesis studies in cattle models to evaluate the susceptibility of cattle to HPAI H5N1 2.3.4.4b. All animal studies will be performed by ARS
Sub-aim 1.2. Identify differences in pathogenesis using RT-qPCR, serology, and pathology.
Aim 2. Evaluate the efficacy of mRNA-LNP HPAI H5N1 2.3.4.4b vaccine in cattle.
Sub-aim 2.1. Determine the optimal dose of mRNA HPAI H5N1 2.3.4.4b vaccine in Holstein calves and cattle.
Sub-aim 2.2. Evaluate the efficacy of mRNA-LNP HPAI H5N1 2.3.4.4b vaccine in Holstein calves and cattle.
Aim 3. Determine the apparent seroprevalence or virus exposure of HPAI in commercial dairy herds.
Sub-aim 3.1. Acquire sera and milk from commercial dairy herds with and without evidence of HPAI H5 infection in the United States.
Sum-aim 3.2. Assess exposure and immunologic response using RT-qPCR and hemagglutinin inhibition (HI) assay using a de-selected H5.