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Antibody and Vaccine production in Plants

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Antibody and Vaccine production in Plants Plant biopharming of monoclonal antibodies Virus Research 111 (2005) 93 100 Kisung Ko, Hilary Koprowski – PowerPoint PPT presentation

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Title: Antibody and Vaccine production in Plants


1
Antibody and Vaccine production in Plants
  • Plant biopharming of monoclonal antibodies
  • Virus Research 111 (2005) 93100
  • Kisung Ko, Hilary Koprowski
  • Plant-produced vaccines promise and reality
  • Edward P Rybicki

2
PLANT-DERIVED BIOMEDICALS FOR TREATMENT OF
INFECTIOUS DISEASES

PLANT-DERIVED BIOMEDICALS FOR TREATMENT OF CANCER
 
3
Antibodies
  • Magic bullets
  • Therapeutic inhibit target involved in disease
    progression
  • Diagnostic
  • Prevention of disease
  • Cause cytotoxic death of target cells
  • Act as carriers for radioisotopes, toxins and
    drugs to site of disease

4
Anti-rabies virus mAb
  • After exposure treated with Ab
  • Used to be made in horses
  • First mAb made in transgenic plants
  • 4 genes 2 H, 2 L
  • Transgenic plant for each one and crossing plants
  • Later used single binary vector with two
    promoters

5
Full-size monoclonal antibodies recently
produced in transgenic plants
6
Abs expressed in transgenic plants
Constant domains
Variable Light chain
Variable Heavy chain
Recombinant hinge region
7
Functional Abs
  • Need to be properly folded and assembled
  • Need disulfide bond formation and glycosylation
  • Down stream processing
  • Purification of Ab mostly with Protein A or G
  • Glycosylation is different in plants
  • ß 1,2 Xylose and a 1,3 fucose
  • Retain in ER, only mannose is attached
  • Shorter half-life of Ab

8
Glycosylation of Ab
Full-size Ab Large single-chain Ab Camelid
heavy-chain Ab
Minibodies and Fab fragments dont get
glycosylated
9
Glycosylation in Golgi
10
Antibodies a compelling success story
  • high specificity in vitro and in vivo
    diagnostics
  • low toxicity therapeutic applications
  • high drug approval rates (24 approved mAbs)
  • major products in biotechnology (240 in clinical
    trials)
  • inherently stable human proteins
  • injectable, topical and oral applications
  • applicable for chronic conditions
  • potential long-lasting benefits

11
Production Costs for Antibodies
Production costs
cost in /
gram
hybridomas
1000
transgenic animals
100
transgenic plants
10
Source Daniell et al. (2001) TIPS 6, 219-226
E. coli yeast
Tr. animals andanimal cells
Transgenicplants
12
Comparison of Mammalian and Plant-produced
Antibodies
  • peptide sequence identical
  • correct cleavage of Ig-derived signal peptides
  • kinetics affinity identical
  • stability in seeds gt 30 months
  • antibody types plant system more versatile
    (sIgA)
  • post-translational processing different
  • core glycan identical, terminal sugar different
    plus xylose fucose
  • antigenicity clearance apparently identical
    (shorter half-life)

13
Vaccines
  • Hepatitis B virus surface antigen HBsAg
  • Norwalk virus capsid
  • Vibrio cholerae enterotoxin subunit
  • Animal vaccines
  • Mink enteritis virus - MEV
  • Rabbit haemorrhagic disease virus - RHDV
  • Foot and mouth disease virus - FMDV

14
Oral vaccines
  • First thought edible vaccines good idea
  • Banana a day
  • Oral vaccination
  • Might elicit antigenic tolerance
  • ProdiGene - Got contamination of maize and
    soybean harvest in 2002 with transmissible
    gastroenteritis virus TGEV

15
Past and Future of PMPs
16
Plant produced Vaccines
  • HPV L1 forms VLPs can protect
  • Measles virus haemagglutinin
  • HBsAg
  • Porcine TGEV
  • Tetanus toxin
  • Vacinia virus B5
  • Allergy vaccines
  • HPV
  • HIV gp41
  • Newcastle disease virus
  • Rotavirus VP7

17
Cancer Vaccines
  • LSBC - Large Scale Biology Crop
  • Individually tailored single chain variable
    region Ab fragments from patients with
    Non-Hodgkin lymphomas
  • Colorectal cancer antigen
  • Cervical Cancer HPV E7

18
Vaccines against biothreat agents
  • Biodefence
  • Anthrax
  • Plague
  • Ricin
  • Haemorrhagic fever

19
PMP Development - Highlights
  • Series of plant-derived vaccines from Arizona
    State University have completed clinical trials
  • Prodigene has trialled two plant-derived vaccines
  • LSBC pipeline of cancer vaccines prior to
    insolvency
  • Guardian Bioscience coccidiosis vaccine, CFIA
    phase II ongoing
  • Fraunhofer CMB, rabies vaccine trialled in humans
  • DowAgro Newcastle disease vaccine, approved Feb
    2006
  • Heberbiovac (Cuba) approved antibody for HepB
    vaccine purification

20
Current Challenges in Molecular Farming
  • yield of recombinant proteins
  • real quantitative comparison (TSP vs
    pg/cell/24h)
  • protein stability (proteases)
  • post-translational modification(s)
  • backcrossing in elite lines
  • extraction and downstream processing
  • QA, QC and substantial equivalence
  • clinical trials regulatory approval

21
Regulatory Challenges for PMP
  • loci of transgene insertion
  • expression properties and levels, including PTM
  • effects of the transgene on the expression of
    flanking endogenous genes
  • master line banking to ensure product consistency
  • contamination with animal excreta, pesticides,
    organic fertiliser
  • procedures for detection and removal of weeds and
    pests
  • cultivation variables

22
Roadmap Plants for the Future
Plant production platforms
  • Vitamines
  • Fatty acids
  • Enzymes
  • Bio-polymers
  • Pigments
  • Pharmaceutical products
  • Fibers

Health food and quality
  • Amino acids
  • Oil
  • Starch

Plant protection
Efficient agriculture
Stress resistance
  • Viruses
  • Nematodes
  • Fungi
  • Insects
  • Cold
  • Drought
  • Salinization
  • Bt technology
  • Herbicide resistance

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2005
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