Heat-stable oral alga-based vaccine protects mice from Staphylococcus aureus infection.
While 15 million deaths per year are caused by communicable pathogens worldwide, health care authorities emphasize the considerable impact of poverty on the incidence of infectious diseases. The emergence of antigen-expressing plant tissues (e.g. rice, tomato, potato) has indicated the potential of land plants for low-cost vaccines in oral immunization programs. In this study, we engineered the chloroplasts of the unicellular green alga Chlamydomonas reinhardtii for the stable expression of the D2 fibronectin-binding domain of Staphylococcus aureus fused with the cholera toxin B subunit (CTB), under the control of rbcL UTRs. Analysis of sera and faeces of mice, fed for 5 weeks with transgenic algae grown in confined Wave Bioreactor, revealed the induction of specific mucosal and systemic immune responses. Algae-based vaccination significantly reduced the pathogen load in the spleen and the intestine of treated mice and protected 80% of them against lethal doses of S. aureus. Importantly, the alga vaccine was stable for more than 1.5 years at room temperature. These results indicate that C. reinhardtii may play an important role in molecular pharming, as it combines the beneficial features of land plant vaccines, while offering unmatched ease of growth compared to other members of the plant kingdom.
Dreesen
Imke A J
IA
Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.
Charpin-El Hamri
Ghislaine
G
Fussenegger
Martin
M
D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D018533:Biomass; D016825:Chlamydomonas reinhardtii / Q000235:genetics*; D002736:Chloroplasts / Q000378:metabolism; D002772:Cholera Toxin / Q000276:immunology; D005612:Freeze Drying; D005744:Gastric Acid / Q000378:metabolism; D005818:Genetic Engineering; D006358:Hot Temperature; D018928:Immunity, Mucosal / Q000276:immunology; D051379:Mice; D030781:Organisms, Genetically Modified; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism; D013203:Staphylococcal Infections / Q000276:immunology* / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000276:immunology*; D013696:Temperature; D013997:Time Factors; D014611:Vaccination
D000941:Antigens; D001428:Bacterial Vaccines; D011956:Receptors, Cell Surface; C034993:ganglioside receptor; D002772:Cholera Toxin