Title

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

Authors

Authors

P. A. Arlen; M. Singleton; J. J. Adamovicz; Y. Ding; A. Davoodi-Semiromi;H. Daniell

Comments

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Abbreviated Journal Title

Infect. Immun.

Keywords

RECOMBINANT V-ANTIGEN; TRANSGENIC TOBACCO CHLOROPLASTS; HETEROLOGOUS; PRIME-BOOST; YERSINIA-PESTIS ANTIGENS; PNEUMONIC PLAGUE; IMMUNE-RESPONSE; PROTECTS MICE; FUSION PROTEIN; CHOLERA-TOXIN; ACTIVE; IMMUNIZATION; Immunology; Infectious Diseases

Abstract

The chloroplast bioreactor is an alternative to fermentation-based systems for production of vaccine antigens and biopharmaceuticals. We report here expression of the plague FIN fusion antigen in chloroplasts. Site-specific transgene integration and homoplasmy were confirmed by PCR and Southern blotting. Mature leaves showed the highest level of transgene expression on the third day of continuous illumination, with a maximum level of 14.8% of the total soluble protein. Swiss Webster mice were primed with adjuvant-containing subcutaneous (s.c.) doses of F1-V and then boosted with either adjuvanted s.c. doses (s.c. FIN mice) or unadjuvanted oral doses (oral F1-V mice). Oral FIN mice had higher prechallenge serum immunoglobulin G1 (IgG1) titers than s.c. F1-V mice. The corresponding serum levels of antigen-specific IgG2a and IgA were 2 and 3 orders of magnitude lower, respectively. After vaccination, mice were exposed to an inhaled dose of 1.02 X 10(6) CFU of aerosolized Yersinia pestis CO92 (50% lethal dose, 6.8 X 10(4) CFU). All control animals died within 3 days. F1-V given s.c. (with adjuvant) protected 33% of the immunized mice, while 88% of the oral F1-V mice survived aerosolized Y. pestis challenge. A comparison of splenic Y. pestis CFU counts showed that there was a 7- to 10-log reduction in the mean bacterial burden in 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.

Journal Title

Infection and Immunity

Volume

76

Issue/Number

8

Publication Date

1-1-2008

Document Type

Article

Language

English

First Page

3640

Last Page

3650

WOS Identifier

WOS:000258480900029

ISSN

0019-9567

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