PROTECTIVE LACTOGENIC IMMUNITY CONFERRED BY AN EDIBLE PEPTIDE VACCINE TO BOVINE ROTAVIRUS PRODUCED IN TRANSGENIC PLANTS

Authors: WIGDOROVITZ, ANDRES - BUENOS AIRES, ARGENTINA; MOZGOVOJ, MARINA - BUENOS AIRES, ARGENTINA; DUS SANTOS, MARIA - BUENOS AIRES, ARGENTINA; PARRENO, VIVIANA - BUENOS AIRES, ARGENTINA; PEREZ-FILGUEIRA, DANIEL - INIT, MADRID, SPAIN; TRONO, KARINA - BUENOS AIRES, ARGENTINA; RIOS, RAUL - INTA-CASTELAR, ARGENTINA; Carrillo, Consuelo; ESCRIBANO, JOSE - INIA, MADRID, SPAIN; Borca, Manuel

Submitted to: Journal of General Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/13/2004
Publication Date: 7/20/2004
Citation: Wigdorovitz, A., Mozgovoj, M., Dus Santos, M.J., Parreno, V., Perez-Filgueira, D.M., Trono, K.G., Rios, R.D., Carrillo, C., Escribano, J.M., Borca, M.V. 2004. Protective lactogenic immunity conferred by an edible peptide vaccine to bovine rotavirus produced in transgenic plants. Journal of General Virology. 85:1825-1832.

Interpretive Summary: The expression of antigens in transgenic plants is an alternative to the classical methodologies for antigen production for the making of experimental vaccines, particularly for the development of edible vaccines. In this regard, it would particularly important the development of edible vaccines to protect individuals against enteric pathogens. Among the economically important enteric pathogens, rotaviruses affect almost all mammalian species. This work presented the development of an experimental vaccine based on the expression of a peptide, eBRV4, of the VP4 protein of bovine rotavirus (BRV), which has been previously described as inducing protection in mice. This peptide was expressed in alfalfa plants associated to a reporter gene, Gus A, an original strategy that allow the colorimetric selection of the transgenic plants expressing the highest levels of the recombinant rotavirus peptide. Interestingly, the transgenic plants obtained were effective in inducing an anti-rotavirus antibody response in adult female mice when administered either parenterally or orally and, more importantly, suckling mice born from immunized female mice were protected against the oral challenge with virulent rotavirus. These results demonstrated, by the first time, the feasibility of using transgenic plants expressing rotavirus antigens as an edible vaccine to prevent disease caused by this virus.

Technical Abstract: Vaccines produced in transgenic plants constitute a promising alternative to conventional immunogens, presenting the possibility of stimulating secretary and systemic immunity against enteric pathogens when administered orally. Protection against enteric pathogens affecting newborn animals requires, in most cases, the stimulation of lactogenic immunity. Here, the group presents the development of an experimental immunogen based on expression of an immunorelevant peptide, eBRV4, of the VP4 protein of bovine rotavirus (BRV), which has been described as harbouring at least one neutralizing epitope as well as being responsible for the adsorption of the virus to epithelial cells. The eBRV4 epitope was efficiently expressed in transgenic alfalfa as a translational fusion protein with the highly stable reporter enzyme Beta-glucuronidase (Beta-GUS), which served as a carrier, stabilized the synthesized peptide and facilitated screening for the higher expression levels in plants. Correlation of expression of the eBRV4 epitope in plants with those presenting the highest Beta-GUS activities was confirmed by a Western blot assay specific for the BRV peptide. The eBRV4 epitope expressed in plants was effective in inducing an anti-rotavirus antibody response in adult female mice when administered either intraperitoneally or orally and, more importantly, suckling mice born from immunized female mice were protected against oral challenge with virulent rotavirus. These results demonstrate the feasibility of inducing lactogenic immunity against an enteric pathogen using an edible vaccine produced in transgenic plants.