ABSTRACT
Traditional phosphodiester lipid vesicles (liposomes) are not stable and could be easily degraded in the gastrointestinal (GI) tract. We prepared a novel lipid based oral delivery system: archaeosomes, made of the polar lipid fraction E (PLFE) extracted from Sulfolobus acidocaldarius, and tested their immunogenic potentials as oral vaccine delivery vehicles. Our study showed that the archaeosomes had significant superior stability in simulated gastric and intestinal fluids, and would help fluorescent labeled antigens to reside longer time in the GI tract after oral administration. The resulted immune responses against model antigen ovalbumin (OVA) were greatly improved, eliciting substantial IgG response systemically as well as IgA response mucosally. In addition, the archaeosomes also facilitated antigen specific CD8(+) T cell proliferation. These data indicate that archaeosomes may be a potential vaccine carrier and adjuvant for effective oral immunization.
Subject(s)
Adjuvants, Immunologic/administration & dosage , Antigens/immunology , Sulfolobus acidocaldarius/immunology , Vaccines/administration & dosage , Administration, Oral , Animals , CD8-Positive T-Lymphocytes , Drug Delivery Systems , Enzyme-Linked Immunosorbent Assay , Female , Gastrointestinal Tract/immunology , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Lipids/immunology , Liposomes/administration & dosage , Liposomes/immunology , Mice , Mice, Inbred BALB C , Ovalbumin/administration & dosage , Ovalbumin/immunology , Vaccines/immunologyABSTRACT
An antiserum to ADP-ribosylated elongation factor 2 (ADPR-EF-2) from S. acidocaldarius was raised in rabbits using stained, homogenized, ADPR-EF-2-containing slices from SDS-gels as a source of antigen. Elongation factor 2 (EF-2) from S. acidocaldarius was cloned in E. coli and the expressed gene product was used in order to adsorb all anti-EF-2 antibodies which do not contain the ADP-ribosyl group within their epitopes, as E. coli is unable to synthesize the ADP-ribosyl acceptor diphthamide. The remaining antibodies were specific to ADP-ribosylated EF-2 from Thermoplasma acidophilum, S. acidocaldarius and Desulfurococcus mucosus. ADP-ribosylated EF-2 from eukaryotic sources also reacted with the adsorbed antiserum as shown for EF-2 isolated from the killi-fish Cynolebias whitei, the mouse species BALB/c and Han/Wistar rats. The adsorbed antiserum did not cross-react with ADP-ribosylated actin or rho protein or with FAD-containing D-amino acid oxidase.
