DNA vaccines

Introduction

Vaccines are one of the most cost-effective medical technologies. Traditional vaccines have many practical disadvantages regarding their production, usage and efficacy. The application of live attenuated vaccines has a severe threat of producing unwanted medical complications in case of uncontrolled growth of vaccine agent. A killed vaccine requires multiple administrations that increase the cost and creates logistical problems. Another problem regarding conventional vaccines is the stress faced by the animals after repeated exposure of the microorganisms either in killed or attenuated form.

DNA vaccine is a modern technology that has eliminated problems associated with traditional vaccines. DNA vaccine has a circular piece of DNA containing the gene needed to produce protective proteins in the cells. The protective proteins elicit an immune response against particular disease causing agent. This article presents a brief review on the usage of DNA vaccines in the field of veterinary medicine all over the world.

History of DNA vaccines

The first report of successful expression of naked plasmid DNA in mouse muscle tissues was from Wolff et al., 1990. Three years later Ulmar et al., 1993 also reported that injection of DNA an antigenic protein is able to produce protective immunity in mice against influenza virus. At present this technology has become very popular among scientists and researchers related to animal and human health.

Advantages of DNA vaccines

The production of DNA vaccine is very easy, rapid and economical because antigen expressing plasmids are amplified in bacterial cultures.
The production of plasmid DNA by bacteria has also eliminated the risk of contamination with viruses and proteins present in eukaryotic cell lines used to produce conventional vaccines.
The DNA molecule is more thermostable between 4^oC to 20^oC than that of traditional vaccines.
The chances of reversion of pathogenic phenotype are impossible as compared with live attenuated vaccines.
DNA vaccines are more rapid to develop against emerging diseases.

Induction of immune response

In Livestock

Much work has been done regarding diseases of bovines and ovine. Bovine herpes virus-I is a common clinical syndrome of cattle and buffalo in many countries. It causes severe damage to animals in many forms. Enhanced immune response has been achieved by intradermal injection of DNA vaccine by Braun et al., 1997 and Van de Hurk et al., 1997. In another study, Cox et al., 1993 have observed high immune response via plasmid DNA injection. Bovine viral diarrhea (BVD) is a wide spread disease of livestock. A study conducted by Harpin et al., 1999 revealed that cattle vaccinated by DNA plasmid encoding major glycoproteins of BVD virus shows satisfactory immune response. Foot and mouth disease (FMD), a disease of cloven foot animals causes sever losses of beef and dairy industry has also been studied by means of biotechnology. A DNA vaccine for FMD has been developed by Beared et al., 1999. Cantlon and his colleagues, 2000 have studied the immune response in cattle and horses to a DNA vaccine against vesicular stomatitis virus that causes a disease of significant importance in livestock. In horses immune response has also been achieved by Romitto et al., 1999 while inoculating horses with VP2 gene of African horse sickness Virus. Pseudotuberclosis in sheep is caused by Corynebacterium pseudotuberclosis. Chaplin and coworkers, 1999 have developed a DNA vaccine against this bacterial disease of sheep. Like the viral and bacterial diseases, parasitic diseases are also controlled by recombinant DNA technology. In a study conducted by Sagodira and his colleagues, 1999 the kids have been immunized from Cryptosporidium parvum after immunization of dams with CP-15 DNA. d'Oliveira et al., 1997 have produced immunity at protective levels to Theileria annulata by merozoite surface antigen in cattle. Presently much work is under development regarding livestock diseases.

In Poultry

Poultry industry is the one of the partially developed industries in developing countries. However, the poultry farming is a little bit organized and mechanized as compared to livestock farming in third world countries. Among vaccines in poultry conventional vaccines occupy a major share. DNA vaccines are new and emerging in this field of veterinary medicine. Infectious bursal disease (IBD) is one of the major viral diseases of poultry. It is caused by IBD virus and is responsible for great losses to poultry producers. The study of Fodor et al., 1999 revealed that immunization of birds with plasmid DNA encoding IBD virus antigen produces protective immunity in chickens. Avian influenza is an emerging poultry disease. Kodihalli et al., 1997 have reported the cross protection among H5N2 influenza virus by DNA vaccine. In another study Kodihalli et al., 2000 have evaluated protection against avian influenza virus with DNA vaccine. Rollier et al., 2000 have studied the humoral response of ducks to DNA immunization against duck hepatitis B virus. In another study Triyatni et al., 1998 have reported the efficacy of DNA vaccines against duck hepatitis B virus infection. The findings of Song et al., 2000 have shown that DNA vaccine encoding Eimeria protein induces protective immunity against Eimeria acervulina challenges. Sakaguchi et al., 1996 have studied the promising effect of linear plasmid DNA vaccine expressing the F protein of New castle disease (ND) virus in chickens.

Conclusions

The above discussion shows that DNA vaccination is a promising technology to prevent diseases in farm animals. The production of DNA vaccines against some diseases is completely feasible and for others it is not such promising. Although the results are satisfactory but continued improvements in vaccine response and reduced costs are necessary before the technology can be commercially developed.

References

1. Beard C. Ward G. Rieder E., Chinsangaram J., Grubman M. J. and Mason P. W. (1999) Development of DNA vaccines for foot-and-mouth disease, evaluation of vaccines encoding replicating and non-replicating nucleic acids in swine. Journal of Biotechnology 73(2-3): 342-249.

2. Braun R., Babiuk L. and van Drunen Littel-van den Hurk S. (1997) Enhanced immune response to an intradermally delivered DNA vaccine expressing a secreted form of BHV-1 gD. Vaccine Research 6: 151-164.

3. Cantlon J. D., Gordy P. W. and Bowen R. A. (2000) Immune responses in mice, cattle and horses to a DNA vaccine for vesicular stomatitis. Vaccine 18(22): 2368-2374.

4. Chaplin P. J., De Rose R., Boyle J. S., Mcwaters P., Kelly J., Tennent I. M., Lew A. M. and Scheerlinck J.P.Y. (1999) Targeting improves the efficacy of a DNA vaccine against Corynebacterium pseudotuberclosis in sheep. Infection and Immunity 67(9): 6434-6438.

5. Cox G. J. M., Zamb T.J. and Babiuk L. A. (1993) Bovine herpesvirus 1: immune response in mice and cattle injected with plasmid DNA. Journal of Virology 67(9): 5664-5667.

6. d'Oliveira C., Feenstra A., Vos H., Osterhaus A. D., Shiels B. R., Cornelissen A. W. and Jongejan F. (1997) Induction of protective immunity to Theileria annulata using two major merozoite surface antigens presented by different delivery systems. Vaccine 15(16): 1796-1804.

7. Fodor I., Horvath E., Fodor N., Nagy E., Rencendorsh A., Vakharia V. N. and Dube S. K. (1999) Induction of protective immunity in chickens immunized with plasmid DNA encoding bursal disease virus antigens. Acta Veterinaria Hungarica 47(4): 481-492.

8. Harpin S., Hurley D. J., Mbikay M., Talbot, B. and Elazhary Y. (1999) Vaccination of cattle with a DNA plasmid encoding the bovine viral diarrhea virus major glycoprotein E2. Journal of General Virology 80: 3137-3144.

9. Kodihalli S., Haynes J. R., Robinson, H. L. and Wabster R. G. (1997) Cross-protection among lethal H5N2 influenza viruses induced by DNA vaccine to the hemagglutinin. Journal of Virology 71(5): 3391-3396.

10. Kodihalli S., Kobasa D. L. and Webster R. G. (2000) Strategies for inducing protection against avian influenza A virus subtypes with DNA vaccines. Vaccine 18(23): 2592-2599.

11. Rollier C., Charollois C., Jamard C., Trepo C. and Cova L. (2000) Early life humoral response of ducks to DNA immunization against hepadnavirus large envelope protein. Vaccine 18(27): 3091-3096.

12. Romito M., Du Plessis D. H. and Viljoen G. J. (1999) Immune responses in a horse inoculated with the VP2 gene of African horsesickness virus. Onderstepoort Journal of Veterinary Research 66: 139-144.

13. Sagodira S., Buzonigatel D., Iochmann S., Naciri M. and Bout D. (1999) Protection of kids against Cryptosporidium parvum infection after immunization of dams with CP15-DNA. Vaccine 17(19): 2346-2355.

14. Sakaguchi M., Nakamura H., Sonoda K., Hamada F. and Hirai, K. (1996) Protection of chickens from Newcastle disease by vaccination with a linear plasmid DNA expressing the F protein of Newcastle disease virus. Vaccine 14(8): 747-752.

15. Song K. D., Lillehoj H. S., Choi K. D., Yun C. H., Parcells M. S., Huynh J. T. and Han, J.Y. (2000) A DNA vaccine encoding a conserved Eimeria protein induces protective immunity against live Eimeria acervulina challenge. Vaccine 19(2-3): 243-252.

16. Triyatni M., Jilbert A. R., Qiao M., Miller D. S. and Burrell C. J. (1998) Protective efficacy of DNA vaccines against duck hepatitis B virus infection. Journal of Virology 72(1): 84-94.

17. Ulmer J. B., Donnelly J. J., Parker S. E., Rhodes G. H., Felgner P. L., Dwarki V. J., Gromkowski S. H., Randall Deck R., DeWitt C. M., Friedman A., Hawe L. A., Leander K. R., Martinez D., Perry H. C., Shiver J. W., Montgomery, D. L. and Liu M. A. (1993) Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259: 1745-1749.

18. van Drunen Littel-van den Hurk S., Braun R. P., Lewis P. J., Karvonen B. C., Babiuk L. A. and Griebel P. J. (1999) Immunization of neonates with DNA encoding a bovine herpesvirus glycoprotein is effective in the presence of maternal antibodies. Viral Immunology 12: 67-77.

19. Wolff J. A., Malone R.W., Williams P., Chong W., Acsadi G., Jani A. and Felgner P. L. (1990) Direct gene transfer into mouse muscle in vivo. Science 247, 1465-1468.

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