Exploiting the Potential of Leader Proteinase Coding Sequence of Foot-and-Mouth Disease Virus to Derive Attenuated STRAINS...COUNTERMEASURES
Foreign Animal Disease Research
2012 Annual Report
1a.Objectives (from AD-416):
The objective of this project is to improve recently developed novel strategies to control Foot-and-Mouth Disease (FMD). By mutating the leader protein (Lpro) coding region of the FMD virus, we were able to grow viruses which are less virulent than wild type viruses. This project will explore the incorporation of additional mutants in the Lpro region to decrease the probability of reversion to virulence and induce protective immune responses.
1b.Approach (from AD-416):
1. Test the virulence in swine of FHA mutant FMDV. In vivo studies will be conducted in swine to test the virulence of an available mutant FMDV strain containing mutations in a conserved domain (FHA) of the virus leader coding region.
2. Construction and in vitro characterization of FMDV strains with mutations in the CTE domain and/or the SAP and/or FHA domains. Several mutant FMDV strains will be constructed by using the infectious clone and targeting conserved residues contained in the CTE region of the leader coding region with the goal of obtaining new stable attenuated phenotypes that have a low probability of reversion to virulent wild type phenotype.
3. Test the virulence in swine of FMDV strains containing multiple mutations in the leader coding region (SAP and/or FHA and/or CTE mutations). In vivo studies will be conducted in swine with newly constructed FMDV containing multiple attenuating mutations in the leader coding region.
4. Test the efficacy of vaccination with attenuated FMDV SAP mutant of serotype A against infection with wild type FMDV of different subtypes and serotypes. Heterologus subypes/serotype specific cross-protection will be assayed by vaccination of swine with FMDV SAP mutant of serotype A followed by challenging with wild type FMDV of serotype A24 or O and/or Asia. The role of induction of protective innate immunity such as the interferon response will be evaluated.
Foot-and-Mouth Disease (FMD) is a highly contagious viral disease that affects cloven-hoofed ruminants. Outbreaks of FMD can have a serious economic impact given the trade restrictions imposed to affected countries by the World Organization of Animal Health (OIE) . This research project seeks to develop novel FMD vaccines, by introducing mutations in one of the FMDV non structural proteins, L pro. Previous studies have shown that mutations in this viral coding region are tolerated and attenuated viruses could be used as vaccines conferring early and presumably long term protection against disease. The objective of this project is to improve this strategy by introducing other mutations in the Lpro region to decrease the probability of reversion to virulence, to increase the stability of the attenuated phenotype and to induce enhanced protective immune responses.
The major accomplishment of this research project, which was initiated in May, 2012 was obtaining post doctoral support for this work as well as characterizing in vitro new Lpro mutants.
No new technologies have been produced or transferred to date from this ongoing work. No peer-reviewed publications have been produced to date from this ongoing work.