Effective plague vaccination via oral delivery of plant cells expressing F1-V antigens in chloroplasts. Export

@article{citeulike:2898865, abstract = {The chloroplast bioreactor is an alternative to fermentation-based systems to produce vaccine antigens and biopharmaceuticals. We report here expression of the plague F1-V fusion antigen in chloroplasts. Site-specific transgene integration and homoplasmy were confirmed by PCR and Southern blots. Mature leaves showed the highest level of transgene expression on the third day of continuous illumination, with a maximum of 14.8\% total soluble protein. Swiss Webster mice were primed with adjuvanted subcutaneous (SC) doses of F1-V and then boosted with either adjuvanted SC (SC F1-V) or unadjuvanted oral (oral F1-V) doses. Oral F1-V mice had higher pre-challenge serum IgG1 titers than those of SC F1-V mice. Corresponding serum levels of antigen-specific IgG2a and IgA were two and three orders of magnitude lower, respectively. After vaccination, mice were exposed to an inhaled dose of aerosolized Y. pestis CO92 of 1.02 x 10(6) CFU (LD50 = 6.8 x 10(4) CFU). All control animals died within three days. SC F1-V (with adjuvant) protected 33\% of immunized mice, while 88\% of oral F1-V-boosted mice survived aerosolized Y. pestis challenge. A comparison of splenic Y. pestis CFU counts showed a seven- to ten-log reduction in the mean bacterial burden of survivors. Taken together, these data indicate that oral booster doses effectively elicit protective immune responses in vivo. In addition, this is the first report of a plant-derived oral vaccine that protected animals from live Y. pestis challenge, bringing the likelihood of lower cost vaccines closer to reality.}, address = {Department of Molecular Biology and Microbiology, College of Medicine, University of Central Florida, Biomolecular Science Building \#20, Room 336, 4000 Central Florida Blvd, Orlando, FL 32816-2364, USA; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, Frederick, MD 21702, U.S.A.}, author = {Arlen, Philip A A. and Singleton, Michael and Adamovicz, Jeffrey J J. and Ding, Yi and Davoodi-Semiromi, Abdolreza and Daniell, Henry}, citeulike-article-id = {2898865}, citeulike-linkout-0 = {http://dx.doi.org/10.1128/IAI.00050-08}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18505806}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18505806}, day = {27}, doi = {10.1128/IAI.00050-08}, issn = {1098-5522}, journal = {Infection and immunity}, keywords = {chloroplast\_expression, plague}, month = {May}, posted-at = {2008-06-16 16:15:24}, priority = {2}, title = {Effective plague vaccination via oral delivery of plant cells expressing F1-V antigens in chloroplasts.}, url = {http://dx.doi.org/10.1128/IAI.00050-08}, year = {2008} }

TY - JOUR ID - citeulike:2898865 L3 - citeulike-article-id:2898865 N2 - The chloroplast bioreactor is an alternative to fermentation-based systems to produce vaccine antigens and biopharmaceuticals. We report here expression of the plague F1-V fusion antigen in chloroplasts. Site-specific transgene integration and homoplasmy were confirmed by PCR and Southern blots. Mature leaves showed the highest level of transgene expression on the third day of continuous illumination, with a maximum of 14.8% total soluble protein. Swiss Webster mice were primed with adjuvanted subcutaneous (SC) doses of F1-V and then boosted with either adjuvanted SC (SC F1-V) or unadjuvanted oral (oral F1-V) doses. Oral F1-V mice had higher pre-challenge serum IgG1 titers than those of SC F1-V mice. Corresponding serum levels of antigen-specific IgG2a and IgA were two and three orders of magnitude lower, respectively. After vaccination, mice were exposed to an inhaled dose of aerosolized Y. pestis CO92 of 1.02 x 10(6) CFU (LD50 = 6.8 x 10(4) CFU). All control animals died within three days. SC F1-V (with adjuvant) protected 33% of immunized mice, while 88% of oral F1-V-boosted mice survived aerosolized Y. pestis challenge. A comparison of splenic Y. pestis CFU counts showed a seven- to ten-log reduction in the mean bacterial burden of survivors. Taken together, these data indicate that oral booster doses effectively elicit protective immune responses in vivo. In addition, this is the first report of a plant-derived oral vaccine that protected animals from live Y. pestis challenge, bringing the likelihood of lower cost vaccines closer to reality. JF - Infection and immunity SN - 1098-5522 AD - Department of Molecular Biology and Microbiology, College of Medicine, University of Central Florida, Biomolecular Science Building #20, Room 336, 4000 Central Florida Blvd, Orlando, FL 32816-2364, USA; Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), 1425 Porter Street, Fort Detrick, Frederick, MD 21702, U.S.A. TI - Effective plague vaccination via oral delivery of plant cells expressing F1-V antigens in chloroplasts. KW - chloroplast_expression KW - plague AU - Arlen, Philip A AU - Singleton, Michael AU - Adamovicz, Jeffrey J AU - Ding, Yi AU - Davoodi-Semiromi, Abdolreza AU - Daniell, Henry PY - 2008/05/27/ UR - http://dx.doi.org/10.1128/IAI.00050-08 ER -