The purpose of this proposal is to develop novel vaccines and test their efficacies to protect poultry from highly pathogenic avian influenza virus (HPAIV) H5N1 infection

The Department of Agriculture Animal and Plant Health Inspection Service awarded the University of Missouri System a $1.999 million cooperative agreement on February 2, 2026, under the Plant and Animal Disease, Pest Control, and Animal Care program (CFDA 10.025) to develop novel vaccines and test their efficacy in protecting poultry from highly pathogenic avian influenza H5N1 (HPAIV H5 clade 2.3.4.4b).

The university will develop and evaluate three vaccine candidates: an NDV LaSota H5 vaccine (NDV-H5) expressing the hemagglutinin of currently circulating HPAIV H5N1 clade 2.3.4.4b and testing its immunogenicity and efficacy in chickens; a chimeric NDV/APMV3-H5 vaccine determining safety, immunogenicity, and efficacy in one-day-old chickens with maternal antibodies against NDV; and a prime-boost combination of chimeric NDV/APMV3-H5 and NDV-H5 vaccines assessing immunogenicity and efficacy against homologous highly pathogenic H5 virus in turkeys. The H5N1 outbreak in domestic poultry and wild birds has caused significant economic losses, egg shortages, food safety issues, and spread to dairy cattle and humans; depopulation measures have failed to control outbreaks effectively.

The cooperative agreement runs through February 1, 2029, with place of performance in the United States. The University of Missouri System is the ultimate recipient.

Two sub-recipients deliver specialized vaccine development support: Kansas State University (sub-award awarded March 10, 2026) develops the novel NDV LaSota H5 vaccine and chimeric NDV/APMV3-H5 vaccine candidates and tests vaccination regimens to overcome maternal antibody interference; Icahn School of Medicine at Mount Sinai (sub-award awarded March 19, 2026) generates avian paramyxovirus-based H5 vaccines through the Garcia-Sastre laboratory for testing in domestic birds.

The HPAIV H5 clade 2.3.4.4B has caused outbreaks in US domestic poultry and wild birds, resulting in significant economic losses and causing EGG shortages and food safety issues. Although depopulation of domestic birds has been employed on impacted and neighboring farms, H5N1 HPAIV outbreaks are still not effectively controlled. Moreover, these viruses spread to and infect different mammals including dairy cattle and humans. Safe and effective vaccines are urgently needed to control current outbreaks in domestic poultry to protect the poultry industry. We have developed newcastle disease virus (NDV) vectored H5 vaccines with diva capabilities and demonstrated that they are safe and efficacious against lethal H5 hpaivs through mass application by coarse spray vaccination. We have also developed an infectious chimeric NDV lasota strain clone (CNDV/APMV3) in which NDV HN and F genes are replaced by respective genes of avian paramyxovirus 3. We plan to use the CNDV/APMV3 to express the clade 2.3.4.4B H5 (CNDV/APMV3-H5) to vaccinate domestic poultry and test different vaccination regimen to overcome interference of NDV vaccine induced maternally derived antibodies (MDA). We plan to have 3 objectives in this application: objective 1 will develop a novel NDV LAS OTA H5 vaccine expressing HA of currently circulating HPAIV H5N1 clade 2.3.4.4B virus (NDV-H5) and investigate its immunogenicity and efficacy in chickens; objective 2 will develop a novel CNDV/APMV3-H5 vaccine expressing the same H5 as described in objective 1, and determine its safety, immunogenicity and efficacy in 1-day-old chickens with MDA against NDV. Objective 3 will determine the immunogenicity and efficacy of a prime-boost CNDV/APMV3-H5 and NDV-H5 vaccination against homologous highly pathogenic H5 virus in turkeys. Our approach will lead to novel, safe, and efficacious H5 vaccines, which can be used in poultry, with diva and overcoming MDA capabilities. The vaccine can also be used as a dual vaccine providing protection not only against H5 influenza viruses but also against NDV to protect the poultry industry and benefit US farmers, poultry producers, and stakeholders.