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Table 1 Highlights of historical and recent activity in virus vaccine biofarming

From: Plant-based vaccines against viruses

Virus and vaccine candidate Reference
Hepatitis B virus  
First expression of HBV surface antigen in plants [4]
Human clinical trial of plant-produced HBsAg [16]
First production of HBsAg in transgenic banana [17]
Use of rTMV-mediated transient expression to produce ~300 mg/kg HBsAg [20]
Use of rBeYDV-mediated transient expression to produce 800 mg/kg HBc Ag [24]
Tabletised lyophilised transgenic lettuce containing HBsAg VLPs is orally immunogenic in mice [19]
Hepatitis C virus  
Use of rTMV to express R9 epitope of E2 protein as CTB fusion [30]
Expression of chimaeric plant virus coat protein molecules containing R9 [31]-[33]
R9-CMV CP VLPs orally immunogenic via feeding of lettuce leaves in rabbits [34]
Mixed Th1/Th2 response in mice to rodlike PMV-E2 epitope chimaeric VLPs [36]
Co-expression of whole E2 and calnexin and calreticulin increases E2 accumulation in plants [37]
Influenza viruses  
Evidence of high-yield expression of H5 haemagglutinin-derived VLPs via transient expression [44]
10 million vaccine dose “rapid fire” milestone by Medicago Inc. in DARPA Blue Angel programme [50]
Human clinical trial of plant-made H5N1 vaccine candidate [47]
HA-only VLPs produced for H7N9 outbreak virus [54]
Phase 1 trials of H1N1pdm and HPAI H5N1 HA-derived plant-made products [48]
Testing of plant-made engineered soluble trimeric HA (H1N1pdm) in mice [58]
Adjuvanting of monomeric H1N1pdm HA with SiO2 and bis-(3′,5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) [59]
Emergency response influenza vaccine candidates made in South Africa [43]
Conjugation of plant-made HA to TMV particles and successful testing in mice [60]
Elicitation of neutralising Ab with elastin-like polypeptide fused with stabilised soluble trimer-forming H5N1 HA [61]
Presentation of M2e epitope on surface of rTMV virions elicits protective immunity to homologous and heterologous challenge in mice [64]
Papillomaviruses  
Proof of efficacy of a plant-made Cottontail rabbit and Rabbit oral papillomavirus vaccines [74],[75]
High yields of HPV-16 L1 and VLPs via agroinfiltration-mediated transient expression or via transplastomic expression [76],[77]
Transplastomic expression of capsomere-forming HPV-16 L1 fused with Escherichia coli LTB as a built-in adjuvant [78]
Successful expression of HPV-8 and Bovine papillomavirus L1 VLPs in plants [79],[80]
Co-expression of HPV-16 L1 with E coli LTB and oral immunisation elicits increased intestinal mucosal IgA responses to L1 [90]
High-yield plant transient expression of chimaeric L1::L2 VLPs and proof of increased breadth of immune response [91]
rPVX CP fusion with L2108–120 epitope yields well and elicits high-titre anti-L2 protein sera in mice [97]
Plant production, scale-up and protective efficacy in mouse model of therapeutic E7GGG-LicKM fusion protein vaccine [85]-[87]
Plant expressed HPV-16 L1 with C-terminal string of E6 and E7 T-cell epitopes is viable prophylactic/therapeutic vaccine candidate [98]
Production and proof of efficacy in mice of soluble E7GGG therapeutic vaccine in transplastomic Chlamydomonas reinhardtii [100]
Proof of yield increase and efficacy in a mouse tumour model of shuffled E7 protein fused to Zera® peptide [102]
Human immunodeficiency virus  
HIV-1 p24 capsid protein expressed successfully in transgenic tobacco [107]
Transgenic maize as production platform for oral vaccine delivery tested using SIV major surface glycoprotein gp130 [108]
Transiently-expressed gp41-derived molecule fused to CTB elicits anti-membrane proximal region (MPR) antibodies in mice [109],[110]
Gag-derived antigens expressed transiently and transgenically as CTL-inducing booster immunogens [113]
High-yield transplastomic expression of Gag VLPs [117]
Phase I clinical trial of anti-HIV MAbs produced in transgenic tobacco [116]
rTMV-based expression of Gag VLP-based deconstructed multiantigens incorporating gp 41 MPER region [124]
First successful published expression of HIV Env in plants: 89.6.P gp140ΔCFI envelope protein expressed at high yield [125]
Transient expression of HIV Env-H5 HA fusion molecule results in VLP formation [126]
Veterinary and “One Health” vaccines  
Production in plants and proof of efficacy in sheep of intact VLPs of Bluetongue virus [128]
Rabies virus vaccines produced in plants and shown to be protective including after oral administration [138]-[141]
Crimean-Congo haemorrhagic fever virus Gc and Gn glycoproteins immunogenic in mice via oral or parenteral administration [144]
Plant-produced Rift Valley fever virus Gn and N proteins immunogenic after feeding mice transgenic Arabidopsis [145]
Expression via rBeYDV and successful immunogenicity trial in mice of Ebola GP1/anti-GP1 MAb HC [158]
Anti-viral therapeutic antibodies  
Production and successful efficacy testing of anti-Rabies virus MAbs made in transgenic tobacco [147]
High-yield production via rBeYDV of anti-Ebolavirus Zaire and West Nile virus MAbs [149],[150]
Transient expression via rTMV, and successful pre- and post-exposure efficacy trial in macaques, of anti-Ebola MAb cocktail [151],[152]
Successful efficacy trial in macaques of the ZMApp therapeutic MAb cocktail [153]
  1. Legend: rTMV = recombinant Tobacco mosaic virus, including ICON vectors. rBeYDV = recombinant Bean yellow dwarf mastrevirus.