Abstract
Respiratory syncytial virus (RSV) is one of the most important pathogens of infancy and early childhood. Here a fruit-based edible subunit vaccine against RSV was developed by expressing the RSV fusion (F) protein gene in transgenic tomato plants. The F-gene was expressed in ripening tomato fruit under the control of the fruit-specific E8 promoter. Oral immunization of mice with ripe transgenic tomato fruits led to the induction of both serum and mucosal RSV-F specific antibodies. The ratio of immunoglobulin subclasses produced in response to immunization suggested that a type 1 T-helper cell immune response was preferentially induced. Serum antibodies showed an increased titer when the immunized mice were exposed to inactivated RSV antigen.
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Alwan WH and Openshaw PJ (1993) Distinct patterns of T-and B-cell immunity to respiratory syncytial virus induced by individual viral proteins. Vaccine 11: 431–437.
Anderson LJ, Hierholzer JC, Tsos C, Hendry RM, Fernie BF, Stone Y and McIntosh K (1985) Antigenic characterization of respiratory syncytial virus strains with monoclonal antibodies. J Infect Dis 151: 626–633.
Arakawa T, Chong DK and Langridge WH (1998) Efficacy of a food plant-based oral cholera toxin B subunit vaccine. Nat Biotechnol 16: 292–297.
Arntzen CJ (1997) High-tech herbal medicine: plant-based vaccines. Nat Biotechnol 15: 221–222.
Belshe RB, Anderson EL and Walsh EE (1993) Immunogenicity of purified F glycoprotein of respiratory syncytial virus: clinical and immune responses to subsequent natural infection in children. J Infect Dis 168: 1024–1029.
Benfey P, Ren L and Chua N-H (1989) The CaMV 35S enhancer contains at least two domains which can confer different developmental and tissue-specific expression patterns. EMBO J 8: 2195–2202.
Bird CR, Smith CJ, Ray JA, Moureau P, Bevan MW, Bird AS, Hughes S, Morris PC, Grierson D and Schuh W (1988) The tomato polygalacturonase gene and ripening-specific expression in transgenic plants. Plant Mol Biol 11: 651–666.
Clark MF and Adams AN (1977) Characteristics of the microplate method of enzyme-linked immunosorbent assay for detection of plant viruses. J Gen Virol 34: 475–483.
Clements JD, Lyon FL, Lowe KL, Farrand AL and El-Morshidy S (1986) Oral immunization of mice with attenuated Salmonella enteritidis containing a recombinant plasmid which codes for production of the B subunit of heat-labile Escherichia coli enterotoxin. Infect Immun 53: 685–692.
Coffin SE and Offit PA (1997) New vaccines against mucosal pathogens: rotavirus and respiratory syncytial virus. Adv Pediatr Infect Dis 13: 333–348.
Collins PL, McIntosh K, Chanock RM and Murphy BR (1996) Respiratory syncytial virus. In: Fields BN, Knipe DM, Howley PM, Chanock RM, Melnick JL, Monath TP, Roizman B and Straus SE (eds) Fields Virology, Vol. 2 (pp. 1313–1351) Lippincott-Raven, Philadelphia, PA.
Deikman J, Kline R and Fischer RL (1992) Organisation of ripening and ethylene regulatory regions in a fruit-specific promoter from tomato (Lycopersicon esculentum). Plant Physiol 100: 2013–2017.
DeVincenzo J (1997) Prevention and treatment of respiratory syncytial virus infections. Adv Pediat Infect Dis 13: 1–47.
Falsey AR and Walsh E (1996) Safety and immunogenicity of a respiratory syncytial virus subunit vaccine (PFP-2) in ambulatory adults over age 60. Vaccine 14: 1214–1218.
Falsey AR and Walsh EE (1998) Relationship of serum antibody to risk of respiratory syncytial virus infection in elderly adults J Infect Dis 177: 463–466.
Fleming DM and Cross KW (1993) Respiratory syncytial virus or influenza? Lancet 342: 1507–1510.
Gaddum RM, Cook RS, Wyld SG, Lopez JA, Bustos R, Melero JA and Taylor G (1996) Mutant forms of the F protein of human respiratory syncytial (RS) virus induce a cytotoxic T lymphocyte response but not a neutralizing antibody response and only transient resistance to RS virus infection. J Gen Virol 77: 1239–1248.
Groothuis JR, King SJ, Hogerman DA, Paradiso PR and Simoes EAF (1998) Safety and immunogenicity of a purified F protein respiratory syncytial virus (PFP-2) vaccine in seropositive children with bronchopulmonary dysplasia. J Infect Dis 177: 467–469.
Hall CB (1992) Respiratory syncytial virus. In: Feigen RD and Cherry JD (eds), Textbook of Pediatric Infectious Diseases, Vol. II (pp. 1633–1656). Saunders, Philadelphia.
Hall CB (1994) Prospects for a respiratory syncytial virus vaccine. Science 265: 1393–1394.
Hamza S and Chupeau Y (1993) Re-evaluation of conditions for plant regeneration and Agrobacterium-mediated transformation from tomato (Lycoperscion esculentum). Exp Bot 44: 1837–1845.
Haq TA, Mason HS, Clements JD and Arntzen CJ (1995) Oral immunization with a recombinant bacterial antigen produced in transgenic plants. Science 268: 714–716.
Johnson PR and Collins PL (1988) The fusion glycoproteins of human respiratory syncytial virus of subgroups A and B: sequence conservation provides a structural basis for antigenic relatedness. J Gen Virol 69: 2623–2628.
Kim HW, Canchola JG, Brandt CD, Pyles G, Chanock RM, Jensen K and Parrott RH (1969) Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. Amer J Epidemiol 89: 422–434.
Koncz C and Schell J (1986) The promoter of Ti-DNA gene 5 controls the tissue-specific expression of chimaeric genes carried by a novel type of Agrobacterium binary vector. Mol Gen Genet 204: 383–396.
Levine S, Klaiber-Franco R and Paradiso PR (1987) Demonstration that glycoprotein G is the attachment protein of respiratory syncytial virus. J Gen Virol 68: 2521–2524.
Lincoln JE, Cordes S, Read E and Fischer RL (1987) Regulation of gene expression by ethylene during Lycopersicon esculentum (tomato) fruit development. Proc Natl Acad Sci USA 84: 2793–2797.
Mason HS, Ball JM, Shi JJ, Jiang X, Estes MK and Arntzen CJ (1996) Expression of Norwalk virus capsid protein in transgenic tobacco and potato and its oral immunogenicity in mice. Proc Natl Acad Sci USA 93: 5335–5340.
Mason HS, Lam DM and Arntzen CJ (1992) Expression of hepatitis B surface antigen in transgenic plants. Proc Natl Acad Sci USA 89: 11745–11749.
McIntosh K and Chanock R (1990) Respiratory syncytial virus. In: Fields B and Knipe D (eds) Virology. Raven, New York
Mosmann TR and Coffman RL (1989) Different patterns of lymphokine secretion lead to different functional properties. Ann Rev Immunol 7: 145–173.
Olmsted RA, Elango N, Prince GA, Murphy BR, Johnson PR, Moss B, Chanock RM and Collins PL (1986) Expression of the F glycoprotein of respiratory syncytial virus by a recombinant vaccinia virus: comparison of the individual contributions of the F and G glycoproteins to host immunity. Proc Natl Acad Sci USA 83: 7462–7466.
Paradiso PR, Hildreth SW, Hogerman DA, Speelman DJ, Lewin EB, Oren J and Smith DH (1994) Safety and immunogenicity of a subunit respiratory syncytial virus vaccine in children 24 to 48 months old. Pediatr Infect Dis J 13: 792–798.
Piedra PA, Grace S, Jewell A, Spinell S, Bunting D, Hogerman DA, Malinoski F and Hiatt PW(1996) Purified fusion protein vaccine protects against lower respiratory tract illness during respiratory syncytial virus season in children with cystic fibrosis. Pediatr Infect Dis J 15: 23–31.
Piedra A, Grace S, Jewell A, Spinelli S, Hogerman DA, Malinoski F and Hiatt PW (1998) Sequential annual administration of purified fusion protein vaccine against respiratory syncytial virus in children with cystic fibrosis. Pediatr Infect Dis J 17: 217–224.
Prober CG and Wang EE (1997) Reducing the morbidity of lower respiratory tract infections caused by respiratory syncytial virus: still no answer. Pediatrics 99: 472–475.
Sambrook J, Fritsch EF and Maniatis T (1989) Molecular Cloning: A Laboratory Manual. 2nd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
Sandhu JS, Osadjan MD, Krasnyanski SF, Domier LL, Korban SS and Buetow DE (1999) Enhanced expression of the human respiratory syncytial virus-F gene in apple protoplasts. Plant Cell Rep 18: 394–397.
Srikiatkhachorn A and Braciale TJ (1997a) Virus-specific CD8+ T lymphocytes downregulate T helper cell type 2 cytokine secretion and pulmonary eosinophilia during experimental murine respiratory syncytial virus infection. J Exp Med 186: 421–432.
Srikiatkhachorn A and Braciale TJ (1997b) Virus-specific memory and effector T lymphocytes exhibit different cytokine responses to antigens during experimental murine respiratory syncytial virus infection. J Virol 71: 678–685.
Strobel S and Mowat AM (1998) Immune responses to dietary antigens: oral tolerance. Immunol Today 19: 173–181.
Tacket CO, Mason HS, Losonsky G, Clements JD, Levine MM and Arntzen CJ (1998) Immunogenicity in humans of a recombinant bacterial antigen delivered in a transgenic potato. Nat Med 4: 607–609.
Tristram DA, Welliver RC, Hogerman DA, Hildreth SW and Paradiso P (1994) Second-year surveillance of recipients of a respiratory syncytial virus (RSV) F protein subunit vaccine, PFP-1: evaluation of antibody persistence and possible disease enhancement. Vaccine 12: 551–556.
Tristram DA, Welliver RC, Mohar CK, Hogerman DA, Hildreth SW and Paradiso P (1993) Immunogenicity and safety of respiratory syncytial virus subunit vaccine in seropositive children 18–36 months old. J Infect Dis 167: 191–195.
Walsh EE, Hall CB, Briselli M, Brandriss MW and Schlesinger JJ (1987) Immunization with glycoprotein subunits of respiratory syncytial virus to protect cotton rats against viral infection. J Infect Dis 155: 1198–1204.
Waris ME, Tsou C, Erdman DD, Day DB and Anderson LJ (1997) Priming with live respiratory syncytial virus (RSV) prevents the enhanced pulmonary inflammatory response seen after RSV challenge in BALB/c mice immunized with formalin-inactivated RSV. J Virol 71: 6935–6939.
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Sandhu, J.S., Krasnyanski, S.F., Domier, L.L. et al. Oral immunization of mice with transgenic tomato fruit expressing respiratory syncytial virus-F protein induces a systemic immune response. Transgenic Res 9, 127–135 (2000). https://doi.org/10.1023/A:1008979525909
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DOI: https://doi.org/10.1023/A:1008979525909


