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Abstract
Background
Enterotoxigenic Escherichia coli (ETEC) strains cause infectious diarrhea and colonize host intestine epithelia via surface-expressed colonization factors. Colonization factor antigen I (CFA/I), a prevalent ETEC colonization factor, is a vaccine target since antibodies directed to this fimbria can block ETEC adherence and prevent diarrhea.
MethodsTwo recombinant antigens derived from CFA/I were investigated with a vaccine adjuvant system 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.
ResultsOwing to their His-tag, recombinant CfaEB and CfaEad, spontaneously bound upon admixture with nanoliposomes containing cobalt-porphyrin phospholipid (CoPoP), as well as a synthetic monophosphoryl lipid A (PHAD) adjuvant. Intramuscular immunization of mice with sub-microgram doses CfaEB or CfaEad admixed with CoPoP/PHAD liposomes elicited serum IgG and intestinal IgA antibodies. The smaller CfaEad antigen benefitted more from liposome display. Serum and intestine antibodies from mice immunized with liposome-displayed CfaEB or CfaEad recognized native CFA/I fimbria as evidenced by immunofluorescence and hemagglutination inhibition assays using the CFA/I-expressing H10407 ETEC strain.
ConclusionThese data show that colonization factor-derived recombinant ETEC antigens exhibit immunogenicity when delivered in immunogenic particle-based formulations.
Details
; Yu, Karl OA 2
; Mabrouk, Moustafa T 1
; Jahagirdar, Dushyant 3
; Wei-Chiao, Huang 1 ; Guerra, Julio A 2 ; He, Xuedan 1
; Ortega, Joaquin 3
; Poole, Steven T 4 ; Hall, Eric R 5 ; Gomez-Duarte, Oscar G 2
; Maciel, Milton 6 ; Lovell, Jonathan F 1
1 Department of Biomedical Engineering, State University of New York at Buffalo, Buffalo, NY, USA
2 Division of Pediatrics Infectious Diseases, Department of Pediatrics, University at Buffalo, Buffalo, NY, USA
3 Department of Anatomy and Cell Biology, McGill University, Montreal, Canada
4 Naval Medical Research Center, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA
5 Naval Medical Research Center, Silver Spring, MD, USA
6 Naval Medical Research Center, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; Department of Microbiology and Immunology, Uniformed Services University Health System, Bethesda, MD, USA