Engineering Foot-and-Mouth Disease Viruses with Improved Growth Properties for Vaccine Development

Abstract

BackgroundNo licensed vaccine is currently available against serotype A foot-and-mouth disease (FMD) in China, despite the isolation of A/WH/CHA/09 in 2009, partly because this strain does not replicate well in baby hamster kidney (BHK) cells.Methodology/Principal FindingsA novel plasmid-based reverse genetics system was used to construct a chimeric strain by replacing the P1 gene in the vaccine strain O/CHA/99 with that from the epidemic stain A/WH/CHA/09. The chimeric virus displayed growth kinetics similar to those of O/CHA/99 and was selected for use as a candidate vaccine strain after 12 passages in BHK cells. Cattle were vaccinated with the inactivated vaccine and humoral immune responses were induced in most of the animals on day 7. A challenge infection with A/WH/CHA/09 on day 28 indicated that the group given a 4-µg dose was fully protected and neither developed viremia nor seroconverted to a 3ABC antigen.Conclusions/SignificanceOur data demonstrate that the chimeric virus not only propagates well in BHK cells and has excellent antigenic matching against serotype A FMD, but is also a potential marker vaccine to distinguish infection from vaccination. These results suggest that reverse genetics technology is a useful tool for engineering vaccines for the prevention and control of FMD.

Esterase D enhances type I interferon signal transduction to suppress foot-and-mouth disease virus replication

“…The viral infection method of FMDV was performed as previously described (Zheng et al, 2013). Briefly, the monolayer PK-15 cells were incubated with FMDV at the multiplicity of infection (MOI) of 0.5.…”

Foot-and-Mouth Disease, an Economically Important Disease of Animals

“…Now a days, scientists have realized many disadvantages of this vaccine and it is very difficult to maintain consistent potency of vaccine and much research continues for developing alternative vaccine strategies that do not require infectious virus viz. proteins/peptides and various recombinant DNA-based strategies, including vectored, virus-like particle (Mohana et al, 2012;Scotti and Rybicki, 2013), gene replacement , empty viral capsids having desired immunogens but lacking infectious nucleic acid and DNA vaccines, synthetic peptide vaccine, epitope based vaccines, chimeric virus vaccines using reverse genetics technology and so on (Seago et al, 2012;Tang et al, 2012b;Zheng et al, 2013). Live attenuated vaccines have also been attempted by serial passaging in non-permissive cell culture or animals (classically), but with limited success.…”

“…1.18 2013a,b, 2014Deb et al, , 2013Madi et al, 2012;Teifke et al, 2012;Madhan Mohan et al, 2013;Xu et al, 2013). Recent developments in prophylaxis/vaccines and therapeutics also need to be utilized to their best potentials along with designing appropriate prevention and control measures for combating FMD and lessening economic losses being caused by this economically important disease of animals (Meeusen et al, 2007;Dhama et al, 2008Dhama et al, , 2013cDhama et al, , 2013dBae et al, 2009;Parida, 2009;Gakuya et al, 2011;Rodriguez and Gay, 2011;Dar et al, 2012a;Kim et al, 2012;Li et al, 2012a;Mahima et al, 2012b;Mohana et al, 2012;Pattnaik et al, 2012;Uddowla et al, 2012;Ayelet et al, 2013;Ding et al, 2013;Zheng et al, 2013;Tiwari et al, 2014).…”

Cross-protective efficacy of engineering serotype A foot-and-mouth disease virus vaccine against the two pandemic strains in swine

“…The first report of serotype A in China was January of 2009, near Wuhan, Hubei province. Occurrences of FMDV serotype A infections were reported in nine other areas within the Chinese mainland during 2009-2010 [7]. However, 2 years after the outbreaks of the first serotype A strain, a new strain (A/GDMM/CHA/2013) was introduced into China from Southeast Asia, and was first reported in regions, continue to threaten FMD-free regions and have attracted a great deal of global interest.…”

“…During 2009-2010, in order to overcome issues with selection and adaptation of vaccine strain and to get better vaccine candidates from field isolates, using reverse genetics technology, we substituted the P1 gene from field isolate A/WH/CHA/09 for P1 gene in a cDNA clone of a vaccine strain (O/CHA/99), creating a chimera (rA/P1-FMDV). The chimera exhibited better growth characteristics in culture than the isolate A/WH/CHA/09 and its inactivated vaccine had good protective effect against epidemic strain A/WH/CHA/09 in cattle [7]. However, whether the vaccine would protect against the new pandemic strain (A/GDMM/CHA/2013) is still unclear.…”