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Induction of protective immunity in swine by recombinant bamboo mosaic virus expressing foot-and-mouth disease virus epitopes.

Yang CD, Liao JT, Lai CY, Jong MH, Liang CM, Lin YL, Lin NS, Hsu YH, Liang SM - BMC Biotechnol. (2007)

Bottom Line: Inoculation of swine with BVP1 virions resulted in the production of anti-FMDV neutralizing antibodies.Furthermore, all BVP1-immunized swine were protected against FMDV challenge.This BaMV-based vector technology may be applied to other vaccines that require correct expression of antigens on chimeric viral particles.

View Article: PubMed Central - HTML - PubMed

Affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, Taiwan. toxogondii@yahoo.com.tw

ABSTRACT

Background: Plant viruses can be employed as versatile vectors for the production of vaccines by expressing immunogenic epitopes on the surface of chimeric viral particles. Although several viruses, including tobacco mosaic virus, potato virus X and cowpea mosaic virus, have been developed as vectors, we aimed to develop a new viral vaccine delivery system, a bamboo mosaic virus (BaMV), that would carry larger transgene loads, and generate better immunity in the target animals with fewer adverse environmental effects.

Methods: We engineered the BaMV as a vaccine vector expressing the antigenic epitope(s) of the capsid protein VP1 of foot-and-mouth disease virus (FMDV). The recombinant BaMV plasmid (pBVP1) was constructed by replacing DNA encoding the 35 N-terminal amino acid residues of the BaMV coat protein with that encoding 37 amino acid residues (T128-N164) of FMDV VP1.

Results: The pBVP1 was able to infect host plants and to generate a chimeric virion BVP1 expressing VP1 epitopes in its coat protein. Inoculation of swine with BVP1 virions resulted in the production of anti-FMDV neutralizing antibodies. Real-time PCR analysis of peripheral blood mononuclear cells from the BVP1-immunized swine revealed that they produced VP1-specific IFN-gamma. Furthermore, all BVP1-immunized swine were protected against FMDV challenge.

Conclusion: Chimeric BaMV virions that express partial sequence of FMDV VP1 can effectively induce not only humoral and cell-mediated immune responses but also full protection against FMDV in target animals. This BaMV-based vector technology may be applied to other vaccines that require correct expression of antigens on chimeric viral particles.

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Serum titers of swine immunized with chimeric virus BVP1. Groups of swine were immunized with 0.5 mg (▲), 5 mg (◆), 10 mg (■) of chimeric virus BVP1 or 5 mg of wild-type virus BaMV-S (○) or PBS (□). Swine sera were collected at the indicated time after immunization. Anti-VP1 titers were determined by ELISA. The animals inoculated with 0.5 mg BVP1 were boosted with the same amount of BVP1 four weeks after priming while those inoculated with 5 mg and 10 mg of BVP1 were boosted six weeks after priming.
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Figure 5: Serum titers of swine immunized with chimeric virus BVP1. Groups of swine were immunized with 0.5 mg (▲), 5 mg (◆), 10 mg (■) of chimeric virus BVP1 or 5 mg of wild-type virus BaMV-S (○) or PBS (□). Swine sera were collected at the indicated time after immunization. Anti-VP1 titers were determined by ELISA. The animals inoculated with 0.5 mg BVP1 were boosted with the same amount of BVP1 four weeks after priming while those inoculated with 5 mg and 10 mg of BVP1 were boosted six weeks after priming.

Mentions: We then evaluated the ability of this chimeric virus to trigger immunity against FMDV in swine. In our first experiment, two groups of three pigs each were given intramuscular injections of 5 mg and 10 mg of BVP1 chimeric virus respectively and boosted with similar amount of BVP1 6 weeks later. Another two groups of two pigs each were vaccinated with 5 mg BaMV-S wild-type virus or PBS buffer respectively as negative controls. Sera obtained from both 5 mg and 10 mg BVP1-immunized swine elicited high levels of anti-VP1 antibodies, as measured by ELISA. In contrast, swine immunized with BaMV-S or PBS buffer all showed little, if any, anti-VP1 antibodies (Fig. 5). Furthermore, neutralizing antibodies (NAs) were detected in the sera of the BVP1-vaccinated groups but not in those of the negative control groups (Table 1). To confirm that even smaller amounts of BVP1 could exhibit similar effects, we immunized swine with either 0.5 mg or 1 mg of BVP1 and boosted with similar amounts of BVP1 4 weeks later. Substantial titers of anti-VP1 antibodies (Fig. 5) and NAs (Table 1) were detected even in the sera of swine given one inoculation of 0.5 mg BVP1, indicating that the chimeric BVP1 virus can effectively trigger specific NAs in swine.


Induction of protective immunity in swine by recombinant bamboo mosaic virus expressing foot-and-mouth disease virus epitopes.

Yang CD, Liao JT, Lai CY, Jong MH, Liang CM, Lin YL, Lin NS, Hsu YH, Liang SM - BMC Biotechnol. (2007)

Serum titers of swine immunized with chimeric virus BVP1. Groups of swine were immunized with 0.5 mg (▲), 5 mg (◆), 10 mg (■) of chimeric virus BVP1 or 5 mg of wild-type virus BaMV-S (○) or PBS (□). Swine sera were collected at the indicated time after immunization. Anti-VP1 titers were determined by ELISA. The animals inoculated with 0.5 mg BVP1 were boosted with the same amount of BVP1 four weeks after priming while those inoculated with 5 mg and 10 mg of BVP1 were boosted six weeks after priming.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2117009&req=5

Figure 5: Serum titers of swine immunized with chimeric virus BVP1. Groups of swine were immunized with 0.5 mg (▲), 5 mg (◆), 10 mg (■) of chimeric virus BVP1 or 5 mg of wild-type virus BaMV-S (○) or PBS (□). Swine sera were collected at the indicated time after immunization. Anti-VP1 titers were determined by ELISA. The animals inoculated with 0.5 mg BVP1 were boosted with the same amount of BVP1 four weeks after priming while those inoculated with 5 mg and 10 mg of BVP1 were boosted six weeks after priming.
Mentions: We then evaluated the ability of this chimeric virus to trigger immunity against FMDV in swine. In our first experiment, two groups of three pigs each were given intramuscular injections of 5 mg and 10 mg of BVP1 chimeric virus respectively and boosted with similar amount of BVP1 6 weeks later. Another two groups of two pigs each were vaccinated with 5 mg BaMV-S wild-type virus or PBS buffer respectively as negative controls. Sera obtained from both 5 mg and 10 mg BVP1-immunized swine elicited high levels of anti-VP1 antibodies, as measured by ELISA. In contrast, swine immunized with BaMV-S or PBS buffer all showed little, if any, anti-VP1 antibodies (Fig. 5). Furthermore, neutralizing antibodies (NAs) were detected in the sera of the BVP1-vaccinated groups but not in those of the negative control groups (Table 1). To confirm that even smaller amounts of BVP1 could exhibit similar effects, we immunized swine with either 0.5 mg or 1 mg of BVP1 and boosted with similar amounts of BVP1 4 weeks later. Substantial titers of anti-VP1 antibodies (Fig. 5) and NAs (Table 1) were detected even in the sera of swine given one inoculation of 0.5 mg BVP1, indicating that the chimeric BVP1 virus can effectively trigger specific NAs in swine.

Bottom Line: Inoculation of swine with BVP1 virions resulted in the production of anti-FMDV neutralizing antibodies.Furthermore, all BVP1-immunized swine were protected against FMDV challenge.This BaMV-based vector technology may be applied to other vaccines that require correct expression of antigens on chimeric viral particles.

View Article: PubMed Central - HTML - PubMed

Affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, Taiwan. toxogondii@yahoo.com.tw

ABSTRACT

Background: Plant viruses can be employed as versatile vectors for the production of vaccines by expressing immunogenic epitopes on the surface of chimeric viral particles. Although several viruses, including tobacco mosaic virus, potato virus X and cowpea mosaic virus, have been developed as vectors, we aimed to develop a new viral vaccine delivery system, a bamboo mosaic virus (BaMV), that would carry larger transgene loads, and generate better immunity in the target animals with fewer adverse environmental effects.

Methods: We engineered the BaMV as a vaccine vector expressing the antigenic epitope(s) of the capsid protein VP1 of foot-and-mouth disease virus (FMDV). The recombinant BaMV plasmid (pBVP1) was constructed by replacing DNA encoding the 35 N-terminal amino acid residues of the BaMV coat protein with that encoding 37 amino acid residues (T128-N164) of FMDV VP1.

Results: The pBVP1 was able to infect host plants and to generate a chimeric virion BVP1 expressing VP1 epitopes in its coat protein. Inoculation of swine with BVP1 virions resulted in the production of anti-FMDV neutralizing antibodies. Real-time PCR analysis of peripheral blood mononuclear cells from the BVP1-immunized swine revealed that they produced VP1-specific IFN-gamma. Furthermore, all BVP1-immunized swine were protected against FMDV challenge.

Conclusion: Chimeric BaMV virions that express partial sequence of FMDV VP1 can effectively induce not only humoral and cell-mediated immune responses but also full protection against FMDV in target animals. This BaMV-based vector technology may be applied to other vaccines that require correct expression of antigens on chimeric viral particles.

Show MeSH
Related in: MedlinePlus