The Last Ten Years of Advancements in Plant-Derived Recombinant Vaccines against Hepatitis B

Abstract

Disease prevention through vaccination is considered to be the greatest contribution to public health over the past century. Every year more than 100 million children are vaccinated with the standard World Health Organization (WHO)-recommended vaccines including hepatitis B (HepB). HepB is the most serious type of liver infection caused by the hepatitis B virus (HBV), however, it can be prevented by currently available recombinant vaccine, which has an excellent record of safety and effectiveness. To date, recombinant vaccines are produced in many systems of bacteria, yeast, insect, and mammalian and plant cells. Among these platforms, the use of plant cells has received considerable attention in terms of intrinsic safety, scalability, and appropriate modification of target proteins. Research groups worldwide have attempted to develop more efficacious plant-derived vaccines for over 30 diseases, most frequently HepB and influenza. More inspiring, approximately 12 plant-made antigens have already been tested in clinical trials, with successful outcomes. In this study, the latest information from the last 10 years on plant-derived antigens, especially hepatitis B surface antigen, approaches are reviewed and breakthroughs regarding the weak points are also discussed.

Parenteral–Oral Immunization with Plant-Derived HBcAg as a Potential Therapeutic Vaccine against Chronic Hepatitis B

“…This could contribute to decrease the HBV reservoir and subsequently to facilitate prevention of hepatitis B and associated diseases. The presented study, together with the others, indicates that plant-expressed proteins could be successfully used in medicine as a cost-effective alternative for current therapeutics [13,40].…”

“…The validity of exploitation of plants as a system for the production of parenteral and oral vaccines and therapeutic proteins has been demonstrated in many reports [13,19,20]. In this study, we have proven that plant-derived HBcAg can be effective as a parenteral primer and oral booster vaccine.…”

“…Nevertheless, a potential plant-derived CHB vaccine would substantially improve public health, especially in developing countries. The main rationale for the use of plants as the source of both injection and oral vaccines is connected with its low-cost, scalable, and safe production [13,19,20,39]. Thanks to effective oral boosting, additional costs associated with HBcAg purification and delivery via injection could be reduced to an indispensable minimum (i.e., priming only).…”

Construction of bicistronic cassette for co-expressing hepatitis B surface antigen and mouse granulocyte-macrophage colony stimulating factor as adjuvant in tobacco plant

“…The ability of plant-produced antigens to induce mucosal and systemic immune responses in laboratory animals as well as clinical trials has been confirmed by various studies (Margolin et al 2018). Several virus-based vaccine candidates including hepatitis B core antigen (HBcAg) and hepatitis B surface antigen (HBsAg) were expressed in transgenic plants (Ehsani et al 1997;Joung et al 2016). However, there are also limitations associated with the transgenic expression, such as complexity of transforming process, time needed for regeneration of stable transformed plant cell, gene positional effects, low expression level and environmental concerns have shifted the studies to transient expression system (Kopertekh and Schiemann 2019).…”

Reconceptualizing Cancer Immunotherapy Based on Plant Production Systems

“…In developing countries, however, where HBV infection continues to predominate, accessibility to vaccines against HBV has been unfeasible due to high cost and lack of medical infrastructure. As a result, from the early onset of plant-based vaccine development, much attention has been placed on the development of an inexpensive, ‘needle-free’ plant-based vaccine against HBV that is stable at room temperature for prolonged periods of time and is both intrinsically safe and efficacious [ 8 , 9 ]. Unfortunately, all of these efforts have focused on creating vaccines to prevent HBV infection and do not reflect efforts to control the onset of liver cancer in chronically infected individuals.…”