Plant-based vaccines against viruses
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REVIEW
Open Access
Plant-based vaccines against viruses Edward P Rybicki
Abstract Plant-made or “biofarmed” viral vaccines are some of the earliest products of the technology of plant molecular farming, and remain some of the brightest prospects for the success of this field. Proofs of principle and of efficacy exist for many candidate viral veterinary vaccines; the use of plant-made viral antigens and of monoclonal antibodies for therapy of animal and even human viral disease is also well established. This review explores some of the more prominent recent advances in the biofarming of viral vaccines and therapies, including the recent use of ZMapp for Ebolavirus infection, and explores some possible future applications of the technology. Keywords: Virus, Vaccine, Biofarming, Plant-made antigen, Monoclonal antibody, HIV, HBV, HCV, HPV, Influenza, Bluetongue, Rabies, Ebola, ZMapp
Introduction The science of “molecular farming”, or the use of plants and plant cell cultures to produce high-value recombinant proteins, started with the production via transgenic tobacco and sunflower of chimaeric human growth hormone in 1986 [1], then of monoclonal antibodies in transgenic tobacco in 1989 [2], and human serum albumin in transgenic tobacco and cell cultures [3]. This was followed from 1992 onwards with the expression of the first candidate virus vaccine antigens: these were Hepatitis B virus (HBV) surface antigen (HBsAg) in 1992 [4], and a VP1 epitope of foot-and-mouth disease virus (FMDV) expressed on the surface of particles of recombinant Cowpea mosaic virus (CPMV) in 1993 ([5] see Table 1). Initially, the prevailing idea for the use of plantproduced vaccines was that these should be delivered in plant material, as edible vaccines – something that was already being questioned as early as 1996 [6]. However, this concept has now largely fallen out of favour, with the realisation that administration of vaccines to humans requires standardisation of dose and some measure of quality control, and the necessity for purification and formulation has largely been accepted [7]. Over the years since 1989, then, many proteins have been expressed as candidate vaccines or therapeutics, and many different plant-based expression systems have been tried, with a
growing trend towards transient expression systems based on infiltration of whole plants with recombinant Agrobacterium tumefaciens (agroinfiltration) and the use of “deconstructed” plant viral vectors (reviewed in [8]). Virus vaccines have been a large and exciting part of this field almost from its beginning, for disease agents ranging from Hepatitis B to C to Foot and mouth disease viruses, from Human papillomavirus and Human rotavirus to ovine Bluetongue and Rabbit haemorrhagic disease viruses, to mention just a few. 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 her
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