SAT2 Foot-and-Mouth Disease Virus Structurally Modified for Increased Thermostability
| Autor: | Bryan Charleston, Francois Frederick Maree, Katherine Anne Scott, Jingshan Ren, Elizabeth E. Fry, Julian Seago, David I. Stuart, Abhay Kotecha |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Antigenicity Immunology Mutant Sodium Chloride Biology Serogroup Microbiology Genomic Instability Virus law.invention 03 medical and health sciences Immunogenicity Vaccine Immune system Immunity law Virology Animals Vaccine Potency Ions Structure and Assembly Temperature Viral Vaccines Hydrogen-Ion Concentration biology.organism_classification Kinetics 030104 developmental biology Amino Acid Substitution Capsid Foot-and-Mouth Disease Virus Insect Science Mutation Recombinant DNA Foot-and-mouth disease virus |
| Zdroj: | Journal of Virology. 91 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | Foot-and-mouth disease virus (FMDV), particularly strains of the O and SAT serotypes, is notoriously unstable. Consequently, vaccines derived from heat-labile SAT viruses have been linked to the induction of immunity with a poor duration and hence require more frequent vaccinations to ensure protection. In silico calculations predicted residue substitutions that would increase interactions at the interpentamer interface, supporting increased stability. We assessed the stability of the 18 recombinant mutant viruses in regard to their growth kinetics, antigenicity, plaque morphology, genetic stability, and temperature, ionic, and pH stability by using Thermofluor and inactivation assays in order to evaluate potential SAT2 vaccine candidates with improved stability. The most stable mutant for temperature and pH stability was the S2093Y single mutant, while other promising mutants were the E3198A, L2094V, and S2093H single mutants and the F2062Y-H2087M-H3143V triple mutant. Although the S2093Y mutant had the greatest stability, it exhibited smaller plaques, a reduced growth rate, a change in monoclonal antibody footprint, and poor genetic stability properties compared to those of the wild-type virus. However, these factors affecting production can be overcome. The addition of 1 M NaCl was found to further increase the stability of the SAT2 panel of viruses. The S2093Y and S2093H mutants were selected for future use in stabilizing SAT2 vaccines. IMPORTANCE Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in cloven-hoofed livestock and wildlife. The control of the disease by vaccination is essential, especially at livestock-wildlife interfaces. The instability of some serotypes, such as SAT2, affects the quality of vaccines and therefore the duration of immunity. We have shown that we can improve the stability of SAT2 viruses by mutating residues at the capsid interface through predictive modeling. This is an important finding for the potential use of such mutants in improving the stability of SAT2 vaccines in countries where FMD is endemic, which rely heavily on the maintenance of the cold chain, with potential improvement to the duration of immune responses. |
| Databáze: | OpenAIRE |
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