Plant-derived antibody

The most widely studied therapeutic proteins produced in plants include monoclonal antibodies for passive immunotherapy and antigens for use as oral vaccines [40]. Antibodies against dental caries, rheumatoid arthritis, cholera, E. coli diarrhea, malaria, certain cancers, Norwalk virus, HIV, rhinovirus, influenza, hepatitis B virus and herpes simplex virus have been produced in transgenic plants. However, the anti-Streptococcus mutans secretory antibody for the prevention of dental caries is the only plant-derived antibody currently in Phase II clinical trials [40]. Until recently, most antibodies were expressed in tobacco, potato, alfalfa, soybean, rice and wheat [9], It has been estimated that for every 170 tons of harvested tobacco, 100 tons represents harvested leaves. A single hectare could thus yield 50 kg of secretory IgA [3, 41]. Furthermore, it has been estimated that the cost of antibody production in plants is half that in transgenic animals and 20 times lower than in mammalian cell cul-... 

Fig. 15.4 Structure of glycans N-linked to IgG molecules expressed in hybridomas and transgenic plants. Glycans N-linked to plant-derived antibodies are structurally different from their mammalian counterparts. In contrast with antibodies produced in alfalfa, antibodies produced in tobacco plants present a very high glycan heterogeneity.

For other plant-derived antibodies, stability was shown to be similar to mammalian counterparts. For instance, a humanized anti-herpes simplex virus monoclonal antibody (IgGl) was expressed in soybean and showed stability in human semen and cervical mucus over 24 h similar to the antibody obtained from mammalian cell culture. In addition, the plant-derived and mammalian antibodies were tested in a standard neutralization assay with no apparent differences in their ability to neutralize HSV-2. As glycans may play a role in immune exclusion mechanisms in mucus, the diffusion of these monoclonal antibodies in human cerival mucus was tested. No differences were found in terms of the prevention of vaginal HSV-2 transmission in a mouse model, i.e. the plant-derived antibody provided efficient protection against a vaginal inoculum of HSV-2 [58]. This shows that glycosylation differences do not necessarily affect efficacy. 

In general, diagnostic tests that look for a particular protein of interest use biologically derived antibodies, usually from mice. However, proteins, DNA, RNA, and other biologicals may be derived from a variety of organisms like bacteria, yeast, plants, and other mammals for use as diagnostics. 

In order to compare the specific activity of plant-derived C5-1 to that of the hybridoma-derived antibody, the antigen-binding capacity of antibodies produced in each system was assayed by enzyme-linked immunosorbent assay (ELISA). As shown in Table 1.2, antibodies from both sources demonstrated similar binding characteristics against human IgGs [8]. Furthermore, the stability of alfalfa-derived C5-1 in the blood stream of Balb/c mice was comparable to that of the hybridoma-derived IgG [8]. 

Wigdorovitz et al. [39] used a TMV expression vector to produce VP1, the 26-kDa structural protein from FMDV, and tested it in mice. Mice injected intraperitoneally with leaf extracts prepared from infected plants mounted an antibody response against the plant-derived protein. All immunized mice were protected when challenged with virulent FMDV. One-year old calves immunized with plant extracts containing VP1 also developed FMDV-specific antibody responses. 

Fig. 8.10 Titers of antibodies at day 50 induced by plant-derived CTB-2L21 recombinant protein. Balb/c mice were intraperitoneally immunized with leaf extract from CTB-2L21 transgenic plants. Animals were boosted at days 21 and 35. Each mouse received 20 pg of CTB-2L21 recombinant protein. Individual samples of mouse serum were titrated against 2L21 synthetic peptide,VP2 protein and a control peptide (amino acids 122-135 of hepatitis B virus surface antigen). Titers were expressed as the highest serum dilution to yield twice the absorbance mean of preimmune sera. M1-M6 mice 1 to 6 2L21 epitope from the VP2 protein of the canine parvovirus CTB cholera toxin B VP2 protein of the canine parvovirus that includes the 2L21 epitope.

First plant-derived recombinant antibody - full-size IgG in tobacco 2... 

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