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Mucosal delivery of antigens using adsorption to bacterial spores.
- Source :
-
Vaccine [Vaccine] 2010 Jan 22; Vol. 28 (4), pp. 1021-30. Date of Electronic Publication: 2009 Nov 13. - Publication Year :
- 2010
-
Abstract
- The development of new-generation vaccines has followed a number of strategic avenues including the use of live recombinant bacteria. Of these, the use of genetically engineered bacterial spores has been shown to offer promise as both a mucosal as well as a heat-stable vaccine delivery system. Spores of the genus Bacillus are currently in widespread use as probiotics enabling a case to be made for their safety. In this work we have discovered that the negatively charged and hydrophobic surface layer of spores provides a suitable platform for adsorption of protein antigens. Binding can be promoted under conditions of low pH and requires a potent combination of electrostatic and hydrophobic interactions between spore and immunogen. Using appropriately adsorbed spores we have shown that mice immunised mucosally can be protected against challenge with tetanus toxin, Clostridium perfringens alpha toxin and could survive challenge with anthrax toxin. In some cases protection is actually greater than using a recombinant vaccine. Remarkably, killed or inactivated spores appear equally effective as live spores. The spore appears to present a bound antigen in its native conformation promoting a cellular (T(h)1-biased) response coupled with a strong antibody response. Spores then, should be considered as mucosal adjuvants, most similar to particulate adjuvants, by enhancing responses against soluble antigens. The broad spectrum of immune responses elicited coupled with the attendant benefits of safety suggest that spore adsorption could be appropriate for improving the immunogenicity of some vaccines as well as the delivery of biotherapeutic molecules.
- Subjects :
- Adsorption
Animals
Anthrax prevention & control
Antibodies, Bacterial blood
Clostridium Infections prevention & control
Female
Mice
Mice, Inbred BALB C
Protein Binding
T-Lymphocytes immunology
Tetanus prevention & control
Antigens, Bacterial chemistry
Antigens, Bacterial immunology
Bacillus subtilis chemistry
Bacillus subtilis immunology
Spores, Bacterial chemistry
Spores, Bacterial immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2518
- Volume :
- 28
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Vaccine
- Publication Type :
- Academic Journal
- Accession number :
- 19914191
- Full Text :
- https://doi.org/10.1016/j.vaccine.2009.10.127