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

Hepatitis B virus

First expression of HBV surface antigen in plants

Human clinical trial of plant-produced HBsAg

First production of HBsAg in transgenic banana

Use of rTMV-mediated transient expression to produce ~300 mg/kg HBsAg

Use of rBeYDV-mediated transient expression to produce 800 mg/kg HBc Ag

Tabletised lyophilised transgenic lettuce containing HBsAg VLPs is orally immunogenic in mice

Hepatitis C virus

Use of rTMV to express R9 epitope of E2 protein as CTB fusion

Expression of chimaeric plant virus coat protein molecules containing R9

R9-CMV CP VLPs orally immunogenic via feeding of lettuce leaves in rabbits

Mixed Th1/Th2 response in mice to rodlike PMV-E2 epitope chimaeric VLPs

Co-expression of whole E2 and calnexin and calreticulin increases E2 accumulation in plants

Influenza viruses

Evidence of high-yield expression of H5 haemagglutinin-derived VLPs via transient expression

10 million vaccine dose “rapid fire” milestone by Medicago Inc. in DARPA Blue Angel programme

Human clinical trial of plant-made H5N1 vaccine candidate

HA-only VLPs produced for H7N9 outbreak virus

Phase 1 trials of H1N1pdm and HPAI H5N1 HA-derived plant-made products

Testing of plant-made engineered soluble trimeric HA (H1N1pdm) in mice

Adjuvanting of monomeric H1N1pdm HA with SiO₂ and bis-(3′,5′)-cyclic dimeric guanosine monophosphate (c-di-GMP)

Emergency response influenza vaccine candidates made in South Africa

Conjugation of plant-made HA to TMV particles and successful testing in mice

Elicitation of neutralising Ab with elastin-like polypeptide fused with stabilised soluble trimer-forming H5N1 HA

Presentation of M2e epitope on surface of rTMV virions elicits protective immunity to homologous and heterologous challenge in mice

Papillomaviruses

Proof of efficacy of a plant-made Cottontail rabbit and Rabbit oral papillomavirus vaccines

High yields of HPV-16 L1 and VLPs via agroinfiltration-mediated transient expression or via transplastomic expression

Transplastomic expression of capsomere-forming HPV-16 L1 fused with Escherichia coli LTB as a built-in adjuvant

Successful expression of HPV-8 and Bovine papillomavirus L1 VLPs in plants

Co-expression of HPV-16 L1 with E coli LTB and oral immunisation elicits increased intestinal mucosal IgA responses to L1

High-yield plant transient expression of chimaeric L1::L2 VLPs and proof of increased breadth of immune response

rPVX CP fusion with L2_108–120 epitope yields well and elicits high-titre anti-L2 protein sera in mice

Plant production, scale-up and protective efficacy in mouse model of therapeutic E7GGG-LicKM fusion protein vaccine

Plant expressed HPV-16 L1 with C-terminal string of E6 and E7 T-cell epitopes is viable prophylactic/therapeutic vaccine candidate

Production and proof of efficacy in mice of soluble E7GGG therapeutic vaccine in transplastomic Chlamydomonas reinhardtii

Proof of yield increase and efficacy in a mouse tumour model of shuffled E7 protein fused to Zera® peptide

Human immunodeficiency virus

HIV-1 p24 capsid protein expressed successfully in transgenic tobacco

Transgenic maize as production platform for oral vaccine delivery tested using SIV major surface glycoprotein gp130

Transiently-expressed gp41-derived molecule fused to CTB elicits anti-membrane proximal region (MPR) antibodies in mice

Gag-derived antigens expressed transiently and transgenically as CTL-inducing booster immunogens

High-yield transplastomic expression of Gag VLPs

Phase I clinical trial of anti-HIV MAbs produced in transgenic tobacco

rTMV-based expression of Gag VLP-based deconstructed multiantigens incorporating gp 41 MPER region

First successful published expression of HIV Env in plants: 89.6.P gp140ΔCFI envelope protein expressed at high yield

Transient expression of HIV Env-H5 HA fusion molecule results in VLP formation

Veterinary and “One Health” vaccines

Production in plants and proof of efficacy in sheep of intact VLPs of Bluetongue virus

Rabies virus vaccines produced in plants and shown to be protective including after oral administration

Crimean-Congo haemorrhagic fever virus Gc and Gn glycoproteins immunogenic in mice via oral or parenteral administration

Plant-produced Rift Valley fever virus Gn and N proteins immunogenic after feeding mice transgenic Arabidopsis

Expression via rBeYDV and successful immunogenicity trial in mice of Ebola GP1/anti-GP1 MAb HC

Anti-viral therapeutic antibodies

Production and successful efficacy testing of anti-Rabies virus MAbs made in transgenic tobacco

High-yield production via rBeYDV of anti-Ebolavirus Zaire and West Nile virus MAbs

Transient expression via rTMV, and successful pre- and post-exposure efficacy trial in macaques, of anti-Ebola MAb cocktail

Successful efficacy trial in macaques of the ZMApp therapeutic MAb cocktail