Smallpox subunit vaccine produced in planta confers protection in mice

• Published in: Proceedings of the National Academy of Sciences - PNAS 2007-04, Vol.104 (16), p.6864-6869
• Main Authors: Golovkin, Maxim, Spitsin, Sergei, Andrianov, Vyacheslav, Smirnov, Yuriy, Xiao, Yuhong, Pogrebnyak, Natalia, Markley, Karen, Brodzik, Robert, Gleba, Yuri, Isaacs, Stuart N, Koprowski, Hilary
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Administration, Oral; Animals; Antibodies; antibody formation; Antigens; B5 antigen; Biological Sciences; biopharmaceuticals; Botany; Brassica - genetics; Brassica - immunology; Brassica oleracea var. viridis; Cholera Toxin - administration & dosage; Cholera Toxin - immunology; collard greens; Female; Flowers & plants; gene expression; genetic vectors; humoral immunity; Immune response; Immunization; Injections, Intramuscular; intramuscular injection; intranasal administration; intravenous injection; live vaccines; Membrane Glycoproteins - administration & dosage; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Mice; Mice, Inbred BALB C; Nicotiana - genetics; Nicotiana - immunology; Nicotiana tabacum; oral vaccination; Plants; Plants, Genetically Modified - immunology; Proteins; recombinant antigens; recombinant vaccines; Rodents; Smallpox; Smallpox - immunology; Smallpox - prevention & control; Smallpox Vaccine - administration & dosage; Smallpox Vaccine - biosynthesis; Smallpox Vaccine - immunology; Swine; Swine, Miniature; Transgenic animals; Transgenic plants; Vaccination; Vaccines; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - biosynthesis; Vaccines, Subunit - genetics; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - biosynthesis; Vaccines, Synthetic - immunology; Vaccinia virus; Vaccinia virus - genetics; Vaccinia virus - immunology; Variola virus; viral antigens; Viral Envelope Proteins - administration & dosage; Viral Envelope Proteins - biosynthesis; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0701451104

We report here the in planta production of the recombinant vaccinia virus B5 antigenic domain (pB5), an attractive component of a subunit vaccine against smallpox. The antigenic domain was expressed by using efficient transient and constitutive plant expression systems and tested by various immunization routes in two animal models. Whereas oral administration in mice or the minipig with collard-derived insoluble pB5 did not generate an anti-B5 immune response, intranasal administration of soluble pB5 led to a rise of B5-specific immunoglobulins, and parenteral immunization led to a strong anti-B5 immune response in both mice and the minipig. Mice immunized i.m. with pB5 generated an antibody response that reduced virus spread in vitro and conferred protection from challenge with a lethal dose of vaccinia virus. These results indicate the feasibility of producing safe and inexpensive subunit vaccines by using plant production systems.