Table 1.
Examples of recently developed human vaccines in plants (within the last 5 years)
| Year reported | Target pathogen | Type of vaccine | Antigen | Plant host | Animal trials | Human trials | References |
|---|---|---|---|---|---|---|---|
| 2019 | Hepatitis B virus (HBV) | VLP | HBcAg | N. benthamiana and L. sativa | Mice—prime oral boost with lettuce stimulated predominant Th1 response with Th2 after boost | ND | [88] |
| 2021 | Hepatitis E virus (HEV) | Chimaeric VLPs | HBcAg-ORF2 AA551-AA607 immunogenic epitope | N. benthamiana | ND | ND | [89] |
| 2020 | Poliovirus (PV) | Subunit | VP1, VP2, VP3, VP4 | N. tabacum | Mice—SC prime and oral boost with lyophilised leaf material stimulated a humoral response | ND | [61] |
| 2021 | Dengue virus (DENV) | VLPs | C-pRM-E + NSP truncated (lacking NS5) | N. benthamiana | Mice—prime-boost elicited anti-DENV1 antibodies | ND | [90] |
| 2019 | DENV | Antigen-display VLPs | HBcAg-DENV EDIII | N. benthamiana | Mice—animals showed some seroconversion | ND | [91] |
| 2018 | West Nile virus (WNV) | Soluble protein | WNV EDIII | N. benthamiana | Mice—potent humoral and cellular response and protection against WNV challenge | ND | [63] |
| 2021 | WNV | Antigen display VLPS | Phage AP205-WNV EDIII | N. benthamiana | Mice—potent humoral response | ND | [51] |
| 2020 | Zika virus (ZIKV) | RIC | ZIKV mAb and cognate Ag | N. benthamiana | Mice—strong specific antibody titers correlating with Zika neutralisation | ND | [57] |
| 2018 | Yellow fever virus (YFV) | Subunit | E alone & E fused to lichenase | N. benthamiana | Mice & monkeys—strong NAbs stimulated | ND | [96] |
| 2021 | Rotavirus (RV) | VLPs | VP2, VP6, VP7 | N. benthamiana | Rats—stimulated robust Nabs | Adults, toddlers and infants—IgG response and NAbs in infants | [98, 99] |
| 2020 | Norovirus (NoV) | Not specified | Not specified | N. benthamiana | ND | Adults >18 years—results not yet available | [138] |
| 2022 | NoV | VLPs | GI & GIII.4 capsid proteins | N. benthamiana | Rabbits—stimulated strong specific antibody and blocking antibody titers | ND | [102] |
| 2021 | Rabies virus (RABV) | Subunit | RG2 protein | N. benthamiana | Mice—stimulated strong specific antibody titers | ND | [64] |
| 2022 | Anthrax | Subunit | Bacillus anthracis pp-PA83 | N. benthamiana |
Mice & rabbits—strong NAbs stimulated Rabbits—protection against B. anthracis challenge |
Adults >18 years— seroconverted | [66] |
| 2018 | Malaria | VLPs | Pfs25 protein | N. benthamiana | Mice—strong humoral response and transmission blocking activity | Adults >18 years—good antibody responses but low transmission reducing activity | [105, 106] |
| 2019 | Human papillomavirus (HPV) | Chimaeric VLPs | HPV-16 L1-L2 | N. benthamiana | Mice—stimulated HPV-16 L1 NAbs and cross-protection against HPV-58 and -18 | ND | [43] |
| 2018/2021 | Influenza virus | VLPs | H5N1 of 4 different circulating strains—quadrivalent vaccine | N. benthamiana | Mice—strong immunity and protection against challenge | Adults >18 years—strong HI antibody titers and CD4+ T-cell response | [117, 119, 126] |
| 2021 | Influenza virus | VLPs | H5N1 quadrivalent vaccine | N. benthamiana | ND | ND | [120] |
| 2021 | SARS-CoV-2 | VLPs | Modified S1 glycoprotein | N. benthamiana | ND | ND | [125] |
| 2021 | SARS-CoV-2 | Antigen display VLPs | CoV-RBD121 | N. benthamiana | Mice—strong NAbs stimulated | Approval for Phase I | [128] |
| 2021 | SARS-CoV-2 | VLPs | E, M & S1 | N. benthamiana | ND | ND | [130] |
| 2020 | SARS-CoV-2 | Soluble protein | S1, RBD & N | N. benthamiana | Mice—antigen-specific immunogenicity | ND | [131] |
| 2022 | SARS-CoV-2 | Soluble protein | Truncated S1 | N. benthamiana | Mice—low cellular and humoral immunogenicity | ND | [132] |
| 2021 | SARS-CoV-2 | Subunit | RBD fused to human IgG1-Fc | N. benthamiana | Mice & monkeys—strong NAbs stimulated | ND | [67, 68] |
EdIII envelope protein domain III, HBcAg hepatitis B core antigen, mAb monoclonal antibody, NAbs neutralising antibodies, ND not done, NSP non-structural protein, RBD receptor-binding domain, RIC recombinant immune complex, SC subcutaneous, VLP virus-like particle, WNV West Nile virus