Progress 08/01/18 to 03/31/19
Outputs Target Audience:The goal of this project was to develop a universal swine influenza virus vaccine which will be licensed with the USDA for use in swine. The mid-term target audience is regulators at the Center for Veterinary Biologics which will grant a commercial license to this product. The final target audience is the swine industry, specifically swine producers and veterinarians which raise and care for swine. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Technical staff (research scientists) at Cambridge Technologies participated in all aspects of the strain construction and characterization and testing in pigs. Likewise, faculty and student collaborators at South Dakota State University played key roles in strain construction and characterizaiton and testing in pigs How have the results been disseminated to communities of interest?These results are being held confidential as the resulting technology developed in being commercialized by Cambridge Technologies. Once licensed by the USDA Center for Veterinary Biologics the results will be widely publicized and also reported in the scientific literature What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts What was accomplished under these goals?
Vaccination has been the most effective means of controlling influenza virus infections of pigs. However, protective antibody responses are largely strain-specific and are not effective against different influenza viruses. Therefore the development of a vaccine candidate that elicits broad-spectrum protection against diverse swine influenza A viruses (IAV), ie. a universal swine influenza vaccine, is critically needed. Cambridge Technologies has developed a novel recombinant swine influenza neuraminidase (NA) subunit vaccine. A recently completed proof of concept vaccine trial containing the baculovirus-expressed neuraminidase type 1 (BacNA1) protein demonstrated that our vaccine candidate delivered by intramuscular (IM) inoculation provided effective heterologous homosubtypic protection against SIV in pigs. Here we developed a second baculovirus strain that expressed NA2, BacNA2, to broaden coverage to both N1 and N2-containing influenza viruses which represent essentially all contemporary circulating IAVs. To further refine these vaccine antigens for mucosal administration via intranasal (IN) delivery, we generated mutants BacNA1 G147R and BacNA2 D151G. These mutations were previously shown to confer hemagglutinin (HA)-like receptor (sialic acid-containing cell surface proteins) binding properties to NA. Both wild type and mutant NA protein expression were verified by Western blotting and NA activity assay. They were shown to form virus like particles by electron microscopy when expressed by baculovirus. Protection afforded by IM administration of BacNA1/BacNA2 and IN administration of BacNA1 G147R/BacNA2 D151G were assessed in pigs including non-vaccinated controls as well as pigs vaccinated with conventional whole inactivated BacNA1/BacNA2 parental virus vaccines (i.e., swine H1N1 and H1N2). BacNA1/BacNA2 administered IM stimulated a robust anti-NA antibody response as seen by the neuraminidase inhibition assay while both IM and IN vaccination routes stimulated mucosal anti-influenza IgA. In contrast to non-vaccinated control and whole inactivated virus vaccines, pigs vaccinated with NA subunit vaccines were protected against heterologous H1N1 and H3N2 IAV challenges as demonstrated with reduction in IAV shedding in nasal swabs, reduction in IAV titer in bronchoalveolar lavage fluids and lung tissue, and near complete protection from lung lesions. These results, coupled with numerous completed internal trials, demonstrate broad-based immunity to IAV conferred by BacNA1/BacNA2. ?
Publications
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