Progress 02/01/12 to 01/31/17
Outputs
Target Audience:Vaccine researchers, virologists, and immunologists in academia and industry. Changes/Problems:We were delayed in our testing of the IRESes because we had to test an unanticipated larger number of sequences using two different reporter genes. Working with these sequences was harder than anticipated due to their high GC content and secondary structure. We also needed to identify an alternative site for expression within the VACV genome (now identified as the F17R gene). Thus it took longer than anticipated to accomplish our goals, but we are confident that we will be able to secure additional USDA funds to test the vaccine in animals in the near future. We are also planning the development of additional polyvalent animal and human vaccines based on the vectors developed under the support of this grant. What opportunities for training and professional development has the project provided?The work was performed by two graduate students with the help of two undergraduate Honors students, therefore providing training and professional development. How have the results been disseminated to communities of interest?Our results have been disseminated n presentations to the scientific community at national and international scientific meetings and invited seminars. We are currently preparing a number of manuscripts to publish the results obtained for wide dissemination (manuscripts in preparation) that will acknowledge NIFA support. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
We were successful in developing and testing a number of strategies to efficiently and stably express multiple heterologous genes in vaccinia virus (VACV), based on the combined use of bidirectional back-to-back early/late promoters, multiple internal ribosome entry sites (IRESes), and multiple alternative genetic loci in the VACV genome (eg, F17R, D6R, A3L, A6L, and A7L). The data obtained from some of these studies allowed us to secure additional funding from NIH to develop vaccines for Zika virus and to enhance the safety of the VACV vectors for humans and animals. We now plan to seek additional competitive USDA funding to test the immunogenicity and efficacy of the quadrivalent vaccine against bovine respiratory disease complex agents in a collaborative effort with investigators at UConn and other institutions. There would be much to gain from a vaccine vector that is easy to manufacture, heat stable, and capable of protecting animals against a number of diseases that are relevant to agricultural animal species. Cost savings resulting from a single vaccination (versus multiple vaccinations with different vaccines), the lack of a requirement for a cold chain (as it is the case for live attenuated vaccines), as well as the ability to allow DIVA diagnostics, would be essential to sustain the economic viability of the animal agricultural industry in the US.
Publications
- Type:
Conference Papers and Presentations
Status:
Other
Year Published:
2016
Citation:
Rapid Development of Zika Virus Vaccine Candidates, Zika Global Health Symposium, University of Massachusetts Boston, May 2, 2016.
- Type:
Conference Papers and Presentations
Status:
Other
Year Published:
2014
Citation:
SMARTer Vaccines: Next-Generation Vaccinia Virus Vaccine and Therapeutic Vectors, 2014 Conference, London, United Kingdom, October 20-22, 2014.
- Type:
Conference Papers and Presentations
Status:
Other
Year Published:
2015
Citation:
SMARTer Vaccines: Replication-Inducible and -Repressible Vaccinia Viruses as Safer Next-Generation Smallpox Vaccines and Vectors, 2015 CBD S&T Conference, St. Louis, MO, May 12-14, 2015.
- Type:
Conference Papers and Presentations
Status:
Other
Year Published:
2016
Citation:
Zika Virus: Development of Vaccine Candidates for an Unprecedented Emerging Infectious Disease, Pathogen/Host Interactions Symposium, Brandeis University, October 4, 2016.
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Progress 02/01/15 to 01/31/16
Outputs
Target Audience:Vaccine researchers in academia and industry. Changes/Problems:We were delayed in our testing of the internal ribosome entry sites because we had to test an unanticipated larger number of sequences using two different reporter genes. Working with these sequences was harder than anticipated due to their high GC content and secondary structure. In addition, we have only found one IRES sequence that allows high levels of expression (at least two different ones are needed). We are currently modifying one of the most promising sequences (in an effort to remove what we believe are deleterious secondary structures) and feel confident we can then improve expression. We also needed to identify an alternative site for expression of half of the genes. We were able to identify the F17R locus, in addition to the A6L-A7L locus and will now be able to express all 10 genes. Therefore additional time will be needed to complete objective 2 of the project, and a final no-cost extension was requested. We realize it is taking longer than anticipated to reach our objective 2, but we are confident we will able to complete it if we are granted the extension. What opportunities for training and professional development has the project provided?
Nothing Reported
How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals?We will finish the development and in vitro characterization of a quadrivalent DIVA vaccine candidate against the bovine respiratory disease complex. If proven successful, these studies will be expanded to test the immunogenicity and efficacy of this quadrivalent vaccine against bovine respiratory disease complex agents in a collaborative effort with investigators at UConn and other institutions. There would be much to gain from a vaccine vector that is easy to manufacture, heat stable, and capable of protecting animals against a number of diseases that are relevant to agricultural animal species. Cost savings resulting from a single vaccination (versus multiple vaccinations with different vaccines), the lack of a requirement for a cold chain (as it is the case for live attenuated vaccines), as well as the ability to allow DIVA diagnostics, would be essential to sustain the economic viability of the animal agricultural industry in the US.
Impacts
What was accomplished under these goals?
We are in the final stages of testing a number of strategies to efficiently and stably express multiple genes in VACV, based on two strong synthetic promoters currently available, that would allow 10 or more heterologous genes to be expressed at high levels by a single recombinant VACV. These strategies include the use of bidirectional back-to-back synthetic early/late promoters, expression based on a number (at least two) of internal ribosome entry sites using reporter genes, and the use on alternative expression sites within the VACV genome.
Publications
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Progress 02/01/14 to 01/31/15
Outputs
Target Audience: Vaccine researchers in academia and industry. Changes/Problems: We were delayed in our testing of the internal ribosome entry sites because we had to test an unanticipated larger number of sequences using two different reporter genes. Working with these sequences was harder than anticipated due to their high GC content and secondary structure. Therefore additional time will be needed to complete objective 2 of the project, and a no-cost extension was requested. What opportunities for training and professional development has the project provided? This project provided trainingon laboratory techniques and research presentation skillsto agraduate student.. How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals? We will finish the development and in vitro characterization of a quadrivalent DIVA vaccine candidate against the bovine respiratory disease complex. If proven successful, these studies will be expanded to test the immunogenicity and efficacy of this quadrivalent vaccine against bovine respiratory disease complex agents in a collaborative effort with investigators at UConn and other institutions. There would be much to gain from a vaccine vector that is easy to manufacture, heat stable, and capable of protecting animals against a number of diseases that are relevant to agricultural animal species. Cost savings resulting from a single vaccination (versus multiple vaccinations with different vaccines), the lack of a requirement for a cold chain (as it is the case for live attenuated vaccines), as well as the ability to allow DIVA diagnostics, would be essential to sustain the economic viability of the animal agricultural industry in the US.
Impacts
What was accomplished under these goals?
We are in the final stages of testing a number of strategies to efficiently and stably express multiple genes in VACV, based on two strong synthetic promoters currently available, that would allow 10 or more heterologous genes to be expressed at high levels by a single recombinant VACV. These strategies include the use of bidirectional back-to-back synthetic early/late promoters and expression based on a number of internal ribosome entry sites using reporter genes, which we are currently finishing testing in vitro.
Publications
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Progress 02/01/13 to 01/31/14
Outputs
Target Audience: Vaccine researchers in academia and industry. Changes/Problems: We were delayed in our testing of the internal ribosome entry sites because we had to test an unanticipated larger number of sequences using two different reporter genes. Therefore additional time will be needed to complete objective 2 of the project, and a no-cost extension was requested. What opportunities for training and professional development has the project provided?
Nothing Reported
How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals? We will finish the development and in vitro characterization of a quadrivalent DIVA vaccine candidate against the bovine respiratory disease complex. If proven successful, these studies will be expanded to test the immunogenicity and efficacy of this quadrivalent vaccine against bovine respiratory disease complex agents in a collaborative effort with investigators at UConn and other institutions. There would be much to gain from a vaccine vector that is easy to manufacture, heat stable, and capable of protecting animals against a number of diseases that are relevant to agricultural animal species. Cost savings resulting from a single vaccination (versus multiple vaccinations with different vaccines), the lack of a requirement for a cold chain (as it is the case for live attenuated vaccines), as well as the ability to allow DIVA diagnostics, would be essential to sustain the economic viability of the animal agricultural industry in the US.
Impacts
What was accomplished under these goals?
We are in the final stages of testing a number of strategies to efficiently and stably express multiple genes in VACV, based on two strong synthetic promoters currently available, that would allow 10 or more heterologous genes to be expressed at high levels by a single recombinant VACV. These strategies include the use of bidirectional back-to-back synthetic early/late promoters and expression based on a number of internal ribosome entry sites using reporter genes, which we are currently testing in vitro.
Publications
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Progress 02/01/12 to 01/31/13
Outputs
Target Audience: Vaccine researchers in academia and industry. Changes/Problems: We are currently somewhat delayed in our testing of the internal ribosome entry sites because we had to test an unanticipated larger number of sequences using two different reporter genes. What opportunities for training and professional development has the project provided?
Nothing Reported
How have the results been disseminated to communities of interest? Preliminary results were reported as a poster presented at the USDA NRI/AFRI Animal Health and Welfare Project Director Meeting, Chicago, IL, in December 2012. What do you plan to do during the next reporting period to accomplish the goals? We plan to finish the promoter / internal ribosome entry site in vitro characterization shortly. We will then develop and characterize (in vitro) a quadrivalent DIVA vaccine candidate against the bovine respiratory disease complex. If proven successful, these studies will be expanded to test the immunogenicity and efficacy of this quadrivalent vaccine against bovine respiratory disease complex agents in a collaborative effort with investigators at UConn and other institutions. There would be much to gain from a vaccine vector that is easy to manufacture, heat stable, and capable of protecting animals against a number of diseases that are relevant to agricultural animal species. Cost savings resulting from a single vaccination (versus multiple vaccinations with different vaccines), the lack of a requirement for a cold chain (as it is the case for live attenuated vaccines), as well as the ability to allow DIVA diagnostics, would be essential to sustain the economic viability of the animal agricultural industry in the US.
Impacts
What was accomplished under these goals?
We are testing a number of strategies to efficiently and stably express multiple genes in VACV, based on two strong synthetic promoters currently available, that would allow 10 or more heterologous genes to be expressed at high levels by a single recombinant VACV. These strategies include the use of bidirectional back-to-back synthetic early/late promoters and expression based on a number of internal ribosome entry sites using reporter genes, which we are currently testing in vitro.
Publications
- Type:
Conference Papers and Presentations
Status:
Other
Year Published:
2012
Citation:
OConnell, C. M. and Verardi, P. H. 2012. Development of viral vectors for polyvalent animal vaccines. Poster presented at the USDA NRI/AFRI Animal Health and Welfare Project Director Meeting, Chicago, IL.
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