Protective lactogenic immunity conferred by an edible peptide vaccine to bovine rotavirus produced in transgenic plants

Abstract

Vaccines produced in transgenic plants constitute a promising alternative to conventional immunogens, presenting the possibility of stimulating secretory 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 b-glucuronidase (bGUS), 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 bGUS 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.

Expression and immunogenicity of an Escherichia coli K99 fimbriae subunit antigen in soybean

“…Many studies only report antibody responses against plant-derived antigens as the sole measure of the host response (e.g. Khandelwal et al 2004;Tacket et al 2004;Wigdorovitz et al 2004). A few studies (e.g.…”

“…To this end, several groups have taken steps towards edible vaccine development to combat bacterial and viral pathogens responsible for diseases in cattle such as bovine shipping fever (Lee et al 2001), bovine rotavirus (Wigdorovitz et al 2004), transmissible gastroenteritis Tuboly et al 2000), and foot and mouth disease (Dus Santos et al 2002). However, to date no one has demonstrated the feasibility of using a major fimbrial protein as a target subunit antigen, or of using soybean as an ideal vaccine production system to combat ETEC infections.…”

Production of Two Vaccinating Recombinant Rotavirus Proteins in the Milk of Transgenic Rabbits

“…Production of rotavirus antigens or proteins in plants has been achieved but in all cases the expression levels were low (Matsumura et al, 2002;Kim & Langridge, 2003Wu et al, 2003;Yu & Langridge, 2003;Wigdorovitz et al, 2004). On the other hand, the purification of Figure 5.…”

“…Moreover, the problem of the dissemination of transgenic plants containing pharmaceutical proteins has not yet been solved (Ma et al, 2003). Interestingly however, oral administration of plant extracts in lactating mice induced a passive protection of offspring (Wigdorovitz et al, 2004).…”

Oral vaccines: new needs, new possibilities

“…In another trial, an immunorelevant peptide of the VP4 protein of bovine rotavirus, eBRV4, which has been described as harboring at least one neutralizing epitopes and being responsible for the adsorption of the virus to epithelial cells, was expressed in transgenic alfalfa. (107) This eBRV4 epitope expressed in plants was effective in inducing anti-rotavirus antibody response in adult female mice when administered orally or intraperitoneally. Recently, a bovine-human (UK) rotavirus reassortant tetravalent (BRV-TV) and other formulations have been reported in clinical studies to be promising oral vaccine candidates.…”