PhD Student, Research Assistant SUNY-Buffalo Buffalo, New York, United States
Introduction:: His-tagged recombinant CFA/I antigens spontaneously bound with nanoliposomes containing cobalt-porphyrin phospholipid (CoPoP) and a synthetic monophosphoryl lipid A (PHAD) adjuvant. Mice elicited serum and intestinal wash antigen-specific antibodies after sub-microgram doses of antigen/CoPoP/PHAD liposomes vaccinations. Serum and intestine wash antibodies from immunized mice recognized native CFA/I fimbria using the CFA/I-expressing H10407 ETEC strain and proved to be functional. This study provided a strategy for developing the ETEC vaccine by using low-dose recombinant CFA/I antigens.
Materials and Methods:: Two recombinant antigens derived from CFA/I were investigated with a vaccine adjuvant system CoPoP/PHAD that displays soluble antigens on the surface of immunogenic liposomes. The first antigen, CfaEB, is a chimeric fusion protein comprising the minor (CfaE) and major (CfaB) subunits of CFA/I. The second, CfaEad, is the adhesin domain of CfaE. Mice were immunized with sub-microgram doses of antigen/CoPoP/PHAD liposomes vaccines. Serum and intestinal antibodies proved to be functional as evidenced by immunofluorescence and hemagglutination inhibition assays.
Results, Conclusions, and Discussions:: Colonization factor-derived recombinant ETEC antigens exhibit immunogenicity when delivered in immunogenic particle-based formulations. Both CfaEad and CfaEB, exhibited enhanced in vitro uptake by macrophages when complexed with CoPoP/PHAD liposomes. The smaller size of CfaEad may render the protein a hapten-like antigen, which shows greater benefit from particle-based immunization. The display of recombinant CFA/I antigens (CfaEad and CfaEB) on the surface of CoPoP/PHAD liposomes at sub-microgram dosing can elicit systemic and mucosal responses against ETEC compared to other adjuvants. Colonization Factor antigen subunit vaccines delivered in particle format by admixture with CoPoP/PHAD liposome appear to be a worthwhile strategy for further research studies.
