The Twenty-Year Story of a Plant-Based Vaccine Against Hepatitis B: Stagnation or Promising Prospects?

Abstract

Hepatitis B persists as a common human disease despite effective vaccines having been employed for almost 30 years. Plants were considered as alternative sources of vaccines, to be mainly orally administered. Despite 20-year attempts, no real anti-HBV plant-based vaccine has been developed. Immunization trials, based on ingestion of raw plant tissue and conjugated with injection or exclusively oral administration of lyophilized tissue, were either impractical or insufficient due to oral tolerance acquisition. Plant-produced purified HBV antigens were highly immunogenic when injected, but their yields were initially insufficient for practical purposes. However, knowledge and technology have progressed, hence new plant-derived anti-HBV vaccines can be proposed today. All HBV antigens can be efficiently produced in stable or transient expression systems. Processing of injection vaccines has been developed and needs only to be successfully completed. Purified antigens can be used for injection in an equivalent manner to the present commercial vaccines. Although oral vaccines require improvement, plant tissue, lyophilized or extracted and converted into tablets, etc., may serve as a boosting vaccine. Preliminary data indicate also that both vaccines can be combined in an effective parenteral-oral immunization procedure. A partial substitution of injection vaccines with oral formulations still offers good prospects for economically viable and efficacious anti-HBV plant-based vaccines.

Vaccination against Trichinella spiralis: Potential, Limitations and Future Directions

“…Recombinant proteins based in plants can be produced in nuclear-transformed plants, synthesized in the cytoplasm, and can be accu-mulated in different subcellular organelles, or secreted, once an appropriate transit or signal peptides are used [73,74]. Plants are considered an attractive platform for veterinary vaccines, due to low-cost production, sterile delivery, and cold storage/ transportation at ambient temperature, compared to traditional attenuated vaccines, which present some inconvenience in terms of insufficient mass production, residual toxicity, means of transportation, and safety [75].…”

“…Then, vaccine antigens can be protected by plant cell walls from further degradation in the digestive tract, enabling them to reach the gut-associated lymphoid tissue [73].…”

Plant-based vaccines against viruses

“…They followed this with the demonstration that the HBsAg middle protein (M protein) -with the highly immunogenic 55 amino acid pre-S2 region fused at N-terminus of the S protein -could be successfully produced in plants, and elicited stronger humoral immune responses than the S protein when injected into mice [22]. The same group used MagnICON vectors to express over 2 g/kg wet weight of plants of VLP-forming and highly immunogenic HBcAg, the "core" antigen [23]: HBc has considerable potential both as a therapeutic vaccine and as a display vehicle for other peptides, including the HBV preS region [11]. A subsequent paper from the Biodesign Institute group detailed the use of a ssDNA Bean yellow dwarf mastrevirus-based vector system (reviewed here [24]) to produce 800 mg/kg of HBcAg in N benthamiana [25].…”

“…Aspects of this history have been covered recently, and in particular for virus-like particle based vaccines including rotaviruses and Norwalk virus [9], Human papillomaviruses [10] and Hepatitis B virus [11], and so these will not be discussed in detail here except where there is new material to be covered. This review will cover the relevant recent history of virus-specific candidate vaccines and virus-specific therapeutic antibodies made in plants, with a view to providing object examples of successful approaches and especially of dual human/animal use or "One Health" examples (http:// www.onehealthinitiative.com/), in order to help inform future work.…”

Plant Based Edible Vaccines against Poultry Diseases: a Review

“…Other advantages of plant based vaccines are ease of production, scale up and administration, biological encapsulation of candidate antigen, ability to evoke serum and mucosal response, protection against mucosal pathogens, low production cost, room temperature stability, trouble free storage, devoid of human or animal pathogens, free from pyrogens and microbial toxins, needle free administration etc. (Moffat, 1995;Sala et al, 2003;Streatfield, 2005;Chen and Lai, 2013;Pniewski, 2013;Aboul-Ata et al, 2014). …”