Traditional Inactivated Vaccines Research Articles

A mutant of Asia 1 serotype of Foot-and-mouth disease virus with the deletion of an important antigenic epitope in the 3A protein

Foot-and-mouth disease is a highly contagious viral disease of cloven-hoofed animals. The availability of a vaccine for differentiating infected from vaccinated animals (DIVA) is crucial for the control and eradication of Foot-and-mouth disease virus (FMDV). Because traditional inactivated vaccines may contain trace nonstructural proteins interfering with the DIVA, we hypothesized that mutant FMDV with deletion of immunodominant epitopes may be valuable. Our previous study has generated a full-length cDNA clone (pBSAs) of FMDV serotype Asia 1 isolated in China. In this study, a B-cell epitope was identified in the 3A region of a nonstructural protein (NSP) by anti-FMDV cattle sera. Furthermore, we generated recombinant FMDV (rvAs-3A14D) by selectively deleting 14 amino acids (position 91-104) in the 3A region of the NSP. Following in vitro transcription and transfection in BHK-21 cells, we successfully rescued the rvAs-3A14D from BHK-21 cells. Characterization of the rvAs-3A14D revealed that the infectivity, antigenicity, and replication kinetics in BHK-21 cells and virulence in mice of the rvAs-3A14D were similar to that of its parent virus. Notably, the mutant rvAs-3A14D only replicated well in BHK-21 but did poorly in primary calf kidney cells. These data suggest that the recombinant FMDV with deletion of this epitope in the NSP may be potentially used as a candidate inactivated vaccine. Therefore, the application of the marker vaccine and differential diagnostic tests may open a promising new avenue for the development of a vaccine for DIVA.

Promising Multiple-Epitope Recombinant Vaccine against Foot-and-Mouth Disease Virus Type O in Swine

In order to develop a completely safe immunogen to replace the traditional inactivated vaccine, a tandem-repeat multiple-epitope recombinant vaccine against foot-and-mouth disease (FMD) virus (FMDV) type O was developed. It contained three copies each of residues 141 to 160 and 200 to 213 of VP1 of the O/China/99 strain of FMDV coupled with a swine immunoglobulin G heavy-chain constant region (scIgG). The data showed that the multiple-epitope recombinant vaccine elicited high titers of anti-FMDV specific antibodies in swine at 30 days postvaccination (dpv) and conferred complete protection against a challenge with 10³ 50% swine infective doses of the O/China/99 strain. The anti-FMDV specific antibody titers were not significantly different between the multiple-epitope recombinant vaccine and the traditional vaccine (t test, P > 0.05). The number of 50% pig protective doses was 6.47, which is higher than the number recommended by the World Organization for Animal Health. The multiple-epitope recombinant vaccine resulted in a duration of immunity of at least 6 months. We speculate that the multiple-epitope recombinant vaccine is a promising vaccine that may replace the traditional inactivated vaccine for the prevention and control of FMD in swine in the future.

Expression of Foot-and-Mouth Disease Virus Capsid Proteins in Silkworm-Baculovirus Expression System and Its Utilization as a Subunit Vaccine

BackgroundFoot-and-mouth disease (FMD) is a highly contagious disease of livestock that causes severe economic loss in susceptible cloven-hoofed animals. Although the traditional inactivated vaccine has been proved effective, it may lead to a new outbreak of FMD because of either incomplete inactivation of FMDV or the escape of live virus from vaccine production workshop. Thus, it is urgent to develop a novel FMDV vaccine that is safer, more effective and more economical than traditional vaccines.Methodology and Principal FindingsA recombinant silkworm baculovirus Bm-P12A3C which contained the intact P1-2A and 3C protease coding regions of FMDV Asia 1/HNK/CHA/05 was developed. Indirect immunofluorescence test and sandwich-ELISA were used to verify that Bm-P12A3C could express the target cassette. Expression products from silkworm were diluted to 30 folds and used as antigen to immunize cattle. Specific antibody was induced in all vaccinated animals. After challenge with virulent homologous virus, four of the five animals were completely protected, and clinical symptoms were alleviated and delayed in the remaining one. Furthermore, a PD50 (50% bovine protective dose) test was performed to assess the bovine potency of the subunit vaccine. The result showed the subunit vaccine could achieve 6.34 PD50 per dose.ConclusionThe results suggest that this strategy might be used to develop the new subunit FMDV vaccine.