Project Number: 6040-32000-081-020-I
Project Type: Interagency Reimbursable Agreement
Start Date: Jun 1, 2022
End Date: May 31, 2025
An evaluation of the vaccines that are licensed or close to being licensed to potentially include in vaccine challenge studies. The turkey herpesvirus-vectored H5 (HVT-H5) vaccine remains licensed in the U.S. and is in commercial production for use in foreign markets. The H5 gene in this vaccine is a clade 2.2 virus originally isolated from 2006, and it did provide some protection to clade 184.108.40.206c viruses and was generally recommended to be used as the first dose of prime-boost vaccination approach. The 2014-15 inactivated whole influenza A vaccine was based on the gyrfalcon/Washington/2014 strain that was mutated to low pathogenic avian influenza by reverse genetics. Using the same technology a new Reverse Genetics (RG) vaccine is being developed that uses the sequence of a U.S. 2022 strain to provide a homologous gene insert that is changed to have a low pathogenic cleavage site. This vaccine should be available for initial evaluation within 6 weeks. The 2014-15 vaccine virus was developed by the United States Department of Agricultue (USDA), Agricultural Research Service (ARS) and a commercial company completed the licensure and sold the product. The ARS laboratory will make RG vaccines with different neuraminidase genes for consideration as a differentiating infected from vaccinated animals (DIVA) vaccine. The commercial company may also produce their own RG vaccine. The RNAp vaccine is a viral vectored vaccine that is replication restricted, so it has the benefits of a live vaccine but is considered an inactivated vaccine because it can’t complete a replication cycle. This platform is currently used for swine influenza vaccines commercially, and it can also be quickly updated by the manufacturer to have a homologous gene insert. The three vaccines available in 2014-15 should be available during the 2022 outbreak. In addition, a different company has submitted for licensure a different HVT vectored H5 vaccine and the gene insert is more closely related to the 220.127.116.11b virus. This vaccine will also be considered for vaccine studies.
The initial vaccine study will be in Specific Pathogen Free (SPF) layer chickens to evaluate each vaccine using a single dose with virulent challenge to determine a baseline for protection. The standard challenge model will be used and will follow vaccine manufacturer’s minimal times between vaccination and challenge and will evaluate for morbidity and mortality, oropharyngeal and cloacal shedding of challenge virus, and serologic response. Additional studies in layers will be conducted to look for optimal combinations of prime boost vaccines and vaccination protocols to look for optimal protection and duration of immunity with long lived birds. Studies will also be conducted in turkeys to look at single vaccination protection and prime boost response. Studies to evaluate duration of immunity will also be conducted. All studies will be evaluated for morbidity and mortality, oropharyngeal and cloacal shedding of challenge virus, and serologic response. Studies on single vaccination of broilers either in ovo or day of age will be conducted. All studies will be evaluated for morbidity and mortality, oropharyngeal and cloacal shedding of challenge virus, and serologic response. Separate studies may be needed in broiler breeder birds as they are more valuable and longer lived. Vaccination of breeder birds may affect vaccination of the offspring because of maternal antibody. Studies in Pekin ducks, the largest commodity duck species in the U.S. will be conducted using the RNAp and RG vaccines. Single and dual vaccinations will be conducted. Ducks have a poor response to the HVT vector vaccine so these studies will not be repeated. All studies will be evaluated for morbidity and mortality, oropharyngeal and cloacal shedding of challenge virus, and serologic response. Because of the susceptibility of raptors to 18.104.22.168 viruses, consideration for vaccine studies in raptors will be considered. These studies will be based on serologic response only and challenge studies are not proposed. Based on the recent experience of SARS CoV-2, zoos and raptor rehabilitation centers are eager to consider vaccination for their animals. We propose to work with rehabilitation centers with inactivated vaccine to evaluate serologic immune response. This work would need to be coordinated with the commercial supplier of the vaccine, APHIS, and other federal agencies to get approval for this work.