Genetic fusions of a CFA/I/II/IV MEFA (multiepitope fusion antigen) and a toxoid fusion of heat-stable toxin (STa) and heat-labile toxin (LT) of Enterotoxigenic Escherichia coli (ETEC) retain broad anti-CFA and antitoxin antigenicity

PLoS ONE

Volumn 10, Issue 3, 2015, Pages

  Ruan, Xiaosai ^a   Sack, David A ^b   Zhang, Weiping ^a  

^a KANSAS STATE UNIVERSITY   (United States)

^b JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADHESIN; ANTITOXIN; BACTERIAL ANTIGEN; BACTERIAL TOXIN; COLONIZATION FACTOR ANTIGEN; CYCLIC AMP; CYCLIC GMP; ESCHERICHIA COLI ENTEROTOXIN; ESCHERICHIA COLI VACCINE; FREUND ADJUVANT; HEAT LABILE TOXIN; HEAT STABLE TOXIN; IMMUNOGLOBULIN G; MULTIEPITOPE FUSION ANTIGEN; SUBUNIT VACCINE; UNCLASSIFIED DRUG; BACTERIAL VACCINE; BACTERIUM ANTIBODY; COLONIZATION FACTOR ANTIGENS; ENTEROTOXIN; ESCHERICHIA COLI PROTEIN; FIMBRIA PROTEIN; HEAT STABLE TOXIN (E COLI); HEAT-LABILE ENTEROTOXIN, E COLI;

ANIMAL CELL; ANIMAL EXPERIMENT; ANTIBODY PRODUCTION; ANTIBODY RESPONSE; ANTIBODY TITER; ANTIGEN DETECTION; ANTIGEN EXPRESSION; ANTIGENICITY; ARTICLE; BACTERIAL STRAIN; BACTERIAL VIRULENCE; BLOOD SAMPLING; CARBOXY TERMINAL SEQUENCE; COLONY FORMING UNIT; CONTROLLED STUDY; DIARRHEA; DRUG TOLERABILITY; ENTEROTOXIGENIC ESCHERICHIA COLI; EPITOPE MAPPING; FEMALE; FIMBRIA; GENE CONSTRUCT; GENE FUSION; IMMUNE ADHERENCE; IMMUNE RESPONSE; IMMUNIZATION; IMMUNOBLOTTING; IMMUNOGENICITY; MOUSE; NONHUMAN; OPTICAL DENSITY; OVERLAPPING GENE; PLASMID; POLYACRYLAMIDE GEL ELECTROPHORESIS; PROTEIN EXPRESSION; STOP CODON; WESTERN BLOTTING; ANIMAL; BLOOD; GENETICS; IMMUNOLOGY; METABOLISM; PROCEDURES; SERODIAGNOSIS;

ANIMALIA; BACTERIA (MICROORGANISMS); ESCHERICHIA COLI; MUS;

ANIMALS; ANTIBODIES, BACTERIAL; ANTIGENS, BACTERIAL; ARTIFICIAL GENE FUSION; BACTERIAL TOXINS; BACTERIAL VACCINES; ENTEROTOXIGENIC ESCHERICHIA COLI; ENTEROTOXINS; ESCHERICHIA COLI PROTEINS; FIMBRIAE PROTEINS; MICE; NEUTRALIZATION TESTS;

EID: 84925857026     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0121623     Document Type: Article

References (50)

1. Black RE, Cousens S, Johnson HL, Lawn JE, Rudan I, Bassani DG, et al. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet 2010;375:1969-1987. doi: 10.1016/S0140-6736 (10) 60549-1 PMID: 20466419
2. WHO. Future directions for research on enterotoxigenic Escherichia coli vaccines for developing countries. Wkly Epidemiol Rec. 2006;81:97-107. PMID: 16671213
3. Nataro JP, Kaper JB. Diarrheagenic Escherichia coli. Clin Microbiol Rev. 1998;11:142-201. PMID: 9457432
4. Gaastra W, Svennerholm AM. Colonization factors of human enterotoxigenic Escherichia coli (ETEC). Trends Microbiol. 1996;4:444-452. PMID: 8950814
5. Wolf MK. Occurrence, distribution, and associations of O and H serogroups, colonization factor antigens, and toxins of enterotoxigenic Escherichia coli. Clin Microbiol Rev. 1997;10:569-584. PMID: 9336662
6. Zhang W. Perspective of use of vaccines for preventing enterotoxigenic Escherichia coli diarrhea in humans. In: Morabito S, editor. Pathogenic Escherichia coli: molecular and cellular microbiology. Norfolk, UK: Caister Academic Press; 2014. p. 273-302.
7. Boedeker EC. Vaccines for enterotoxigenic Escherichia coli: current status. Curr Opinion Gastroenterol. 2005;21:15-19. PMID: 15687879
8. Zhang W, Sack DA. Progress and hurdles in the development of vaccines against enterotoxigenic Escherichia coli in humans. Expert Rev Vaccines. 2012;11:677-694. doi: 10.1586/erv. 12.37 PMID: 22873126
9. Levine MM. Modern vaccines. Enteric infections. Lancet 1990;335:958-961. PMID: 1970034
10. Svennerholm AM, Wenneras C, Holmgren J, McConnell MM, Rowe B. Roles of different coli surface antigens of colonization factor antigen II in colonization by and protective immunogenicity of enterotoxigenic Escherichia coli in rabbits. Infect Immun. 1990;58:341-346. PMID: 1967593
11. Sommerfelt H, Svennerholm AM, Kalland KH, Haukanes BI, Bjorvatn B. Comparative study of colony hybridization with synthetic oligonucleotide probes and enzyme-linked immunosorbent assay for identification of enterotoxigenic Escherichia coli. J Clin Microbiol. 1988;26:530-534. PMID: 3281978
12. Alam MM, Aktar A, Afrin S, Rahman MA, Aktar S, Uddin T, et al. Antien-specific memory B-cell responses to enterotoxigenic Escherichia coli infection in Banbladeshi Adults. PLoS Negl Trop Dis. 2014;8:e2822. doi: 10.1371/journal.pntd.0002822 PMID: 24762744
13. Evans DG, Evans DJ Jr, Opekun AR, Graham DY. Non-replicating oral whole cell vaccine protective against enterotoxigenic Escherichia coli (ETEC) diarrhea: stimulation of anti-CFA (CFA/I) and anti-enterotoxin (anti-LT) intestinal IgA and protection against challenge with ETEC belonging to heterologous serotypes. FEMS Microbiol Immunol. 1988;1:117-125. PMID: 3078739
14. Evans DJ Jr, Evans DG, Opekun AR, Graham DY. Immunoprotective oral whole cell vaccine for enterotoxigenic Escherichia coli diarrhea prepared by in situ destruction of chromosomal and plasmid DNA with colicin E2. FEMS Microbiol Immunol. 1988;1:9-18. PMID: 3078575
15. Svennerholm AM, Holmgren J, Sack DA. Development of oral vaccines against enterotoxinogenic Escherichia coli diarrhoea. Vaccine 1989;7:196-198. PMID: 2675484
16. Jertborn M, Ahren C, Holmgren J, Svennerholm AM. Safety and immunogenicity of an oral inactivated enterotoxigenic Escherichia coli vaccine. Vaccine 1998;16:255-260. PMID: 9607039
17. Ahren C, Jertborn M, Svennerholm AM. Intestinal immune responses to an inactivated oral enterotoxigenic Escherichia coli vaccine and associated immunoglobulin A responses in blood. Infect Immun. 1998;66:3311-3316. PMID: 9632600
18. Harro C, Sack D, Bourgeois AL, Walker R, DeNearing B, Feller A, et al. A combination vaccine consisting of three live attenuated enterotoxigenic Escherichia coli strains expressing a range of colonization factors and heat-labile toxinsubunit B is well tolerated and immunogenic in a placebo-controlled doubleblind phase I trial in healthy adults. Clin Vaccine Immunol. 2011;18:2118-2127. doi: 10.1128/CVI. 05342-11 PMID: 21994354
19. Turner AK, Terry TD, Sack DA, Londono-Arcila P, Darsley MJ. Construction and characterization of genetically defined aro omp mutants of enterotoxigenic Escherichia coli and preliminary studies of safety and immunogenicity in humans. Infect Immun. 2001;69:4969-4979. PMID: 11447175
20. Clemens JD, Sack DA, Harris JR, Chakraborty J, Neogy PK, Stanton B, et al. Cross-protection by B subunit-whole cell cholera vaccine against diarrhea associated with heat-labile toxin-producing enterotoxigenic Escherichia coli: results of a large-scale field trial. J Infect Dis. 1988;158:372-377. PMID: 3042876
21. Sack DA, Shimko J, Torres O, Bourgeois AL, Francia DS, Gustafsson B, et al. Randomised, doubleblind, safety and efficacy of a killed oral vaccine for enterotoxigenic E. Coli diarrhoea of travellers to Guatemala and Mexico. Vaccine 2007;25:4392-4400. PMID: 17448578
22. Savarino SJ, Hall ER, Bassily S, Wierzba TF, Youssef FG, Peruski LF Jr, et al. Introductory evaluation of an oral, killed whole cell enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine in Egyptian infants. Pediatr Infect Dis J. 2002;21:322-330. PMID: 12075764
23. Svennerholm AM, Tobias J. Vaccines against enterotoxigenic Escherichia coli. Expert Rev Vaccines 2008;7:795-804. doi: 10.1586/14760584.7.6.795 PMID: 18665777
24. Harro C, Chakraborty S, Feller A, DeNearing B, Cage A, Ram M, et al. Refinement of a human challenge model for evaluation of enterotoxigenic Escherichia coli vaccines. Clin Vaccine Immunol. 2011;18:1719-1727. doi: 10.1128/CVI.05194-11 PMID: 21852546
25. Darsley MJ, Chakraborty S, DeNearing B, Sack DA, Feller A, Buchwaldt C, et al. The oral, live attenuated enterotoxigenic Escherichia coli vaccine ACE527 reduces the incidence and severity of diarrhea in a human challenge model of diarrheal disease. Clin Vaccine Immunol. 2012;19:1921-1931. doi: 10. 1128/CVI.00364-12 PMID: 23035175
26. Holmgren J, Bourgeois L, Carlin N, Clements J, Gustafsson B, Lundgren A, et al. Development and preclinical evaluation of safety and immunogenicity of an oral ETEC vaccine containing inactivated E. Coli bacteria overexpressing colonization factors CFA/I, CS3, CS5 and CS6 combined with a hybrid LT/CT B subunit antigen, administered alone and together with dmLT adjuvant. Vaccine 2013;31:2457-2464. doi: 10.1016/j.vaccine.2013.03.027 PMID: 23541621
27. Lundgren A, Leach S, Tobias J, Carlin N, Gustafsson B, Jertborn M, et al. Clinical trial to evaluate safety and immunogenicity of an oral inactivated enterotoxigenic Escherichia coli prototype vaccine containing CFA/I overexpressing bacteria and recombinantly produced LTB/CTB hybrid protein. Vaccine 2013;31:1163-1170. doi: 10.1016/j.vaccine.2012.12.063 PMID: 23306362
28. Frantz JC, Robertson DC. Immunological properties of Escherichia coli heat-stable enterotoxins: development of a radioimmunoassay specific for heat-stable enterotoxins with suckling mouse activity. Infect Immun. 1981;33:193-198. PMID: 6167519
29. Frantz JC, Mellencamp MW. Production and testing of Escherichia coli (LTb) toxoid. In: Acres S, editor. Fourth International Symposium on Neonatal Diarrhea. Saskatoon, Saskatchewan, Canada; 1983. p. 500-517.
30. Qadri F, Ahmed T, Ahmed F, Begum YA, Sack DA, Svennerholm AM. Reduced doses of oral killed enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine is safe and immunogenic in Bangladeshi infants 6-17 months of age: dosing studies in different age groups. Vaccine 2006;24:1726-1733. PMID: 16257098
31. Qadri F, Bhuiyan TR, Sack DA, Svennerholm AM. Immune responses and protection in children in developing countries induced by oral vaccines. Vaccine 2013;31:452-460. doi: 10.1016/j.vaccine.2012. 11.012 PMID: 23153448
32. Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 2013;382:209-222. doi: 10.1016/S0140-6736 (13) 60844-2 PMID: 23680352
33. Qadri F, Asaduzzaman M, Wenneras C, Mohi G, Albert MJ, Abdus Salam M, et al. Enterotoxin-specific immunoglobulin E responses in humans after infection or vaccination with diarrhea-causing enteropathogens. Infect Immun. 2000;68:6077-6081. PMID: 10992527
34. Zhang W, Zhang C, Francis DH, Fang Y, Knudsen D, Nataro JP, et al. Genetic fusions of heat-labile (LT) and heat-stable (ST) toxoids of porcine enterotoxigenic Escherichia coli elicit neutralizing anti-LT and anti-STa antibodies. Infect Immun. 2010;78:316-325. doi: 10.1128/IAI.00497-09 PMID: 19858307
35. Taxt A, Aasland R, Sommerfelt H, Nataro J, Puntervoll P. Heat-stable enterotoxin of enterotoxigenic Escherichia coli as a vaccine target. Infect Immun. 2010;78:1824-1831. doi: 10.1128/IAI.01397-09 PMID: 20231404
36. Liu M, Ruan X, Zhang C, Lawson SR, Knudsen DE, Nataro JP, et al. Heat-labile- and heat-stable-toxoid fusions (LTR192G-STaP13F) of human enterotoxigenic Escherichia coli elicit neutralizing antitoxin antibodies. Infect Immun. 2011;79:4002-4009. doi: 10.1128/IAI.00165-11 PMID: 21788385
37. Zhang C, Knudsen DE, Liu M, Robertson DC, Zhang W, & the STa Toxoid Vaccine Consortium Group. Toxicity and immunogenicity of enterotoxigenic Escherichia coli heat-labile and heat-stable toxoid fusion 3xSTaA14Q-LTS63K/R192G/L211A in a murine model. PloS One 2013;8:e77386. doi: 10.1371/journal. pone.0077386 PMID: 24146989
38. Ruan X, Robertson DC, Nataro JP, Clements JD, Zhang W, & the STa Toxoid Vaccine Consortium Group. Characterization of heat-stable (STa) toxoids of enterotoxigenic Escherichia coli fused to a double mutant heat-labile toxin (dmLT) peptide in inducing neutralizing anti-STa antibodies. Infect Immun 2014;82:1823-1832. doi: 10.1128/IAI.01394-13 PMID: 24549325
39. Ruan X, Knudsen DE, Wollenberg KM, Sack DA, Zhang W. Multiepitope fusion antigen induces broadly protective antibodies that prevent adherence of Escherichia coli strains expressing colonization factor antigen I (CFA/I), CFA/II, and CFA/IV. Clin Vaccine Immunol. 2014;21:243-249. doi: 10.1128/CVI. 00652-13 PMID: 24351757
40. Isidean SD, Riddle MS, Savarino SJ, Porter CK. A systematic review of ETEC epidemiology focusing on colonization factor and toxin expression. Vaccine 2011;29:6167-6178. doi: 10.1016/j.vaccine. 2011.06.084 PMID: 21723899
41. Ofek I, Zafriri D, Goldhar J, Eisenstein BI. Inability of toxin inhibitors to neutralize enhanced toxicity caused by bacteria adherent to tissue culture cells. Infect Immun. 1990;58:3737-3742. PMID: 1699898
42. Perez-Casal J, Swartley JS, Scott JR. Gene encoding the major subunit of CS1 pili of human enterotoxigenic Escherichia coli. Infect Immun. 1990;58:3594-3600. PMID: 1977705
43. Froehlich BJ, Karakashian A, Sakellaris H, Scott JR. Genes for CS2 pili of enterotoxigenic Escherichia coli and their interchangeability with those for CS1 pili. Infect Immun. 1995;63:4849-4856. PMID: 7591145
44. Ruan X, Liu M, Casey TA, Zhang W. A tripartite fusion, FaeG-FedF-LT (192) A2:B, of enterotoxigenic Escherichia coli (ETEC) elicits antibodies that neutralize cholera toxin, inhibit adherence of K88 (F4) and F18 fimbriae, and protect pigs against K88ac/heat-labile toxin infection. Clin Vaccine Immunol. 2011;18:1593-1599. doi: 10.1128/CVI.05120-11 PMID: 21813665
45. National Research Council. Guide for the care and use of laboratory animals. Washington DC: National Academy Press; 1996.
46. Qadri F, Das SK, Faruque AS, Fuchs GJ, Albert MJ, Sack RB, et al. Prevalence of toxin types and colonization factors in enterotoxigenic Escherichia coli isolated during a 2-year period from diarrheal patients in Bangladesh. J Clin Microbiol. 2000;38:27-31. PMID: 10618058
47. Bertschinger HU, Nief V, Tschape H. Active oral immunization of suckling piglets to prevent colonization after weaning by enterotoxigenic Escherichia coli with fimbriae F18. Vet Microbiol. 2000;71:255-267. PMID: 10703708
48. Coddens A, Verdonck F, Tiels P, Rasschaert K, Goddeeris BM, Cox E. The age-dependent expression of the F18+ E. Coli receptor on porcine gut epithelial cells is positively correlated with the presence of histo-blood group antigens. Vet Microbiol. 2007;122:332-341. PMID: 17353102
49. Ruan X, Zhang W. Oral immunization of a live attenuated Escherichia coli strain expressing a holotoxinstructured adhesin-toxoid fusion (1FaeG-FedF-LTA (2) :5LTB) protected young pigs against enterotoxigenic E. Coli (ETEC) infection. Vaccine 2013;31:1458-1463. doi: 10.1016/j.vaccine.2013.01.030 PMID: 23375979
50. Taxt AM, Diaz Y, Bacle A, Grauffel C, Reuter N, Aasland R, et al. Characterization of immunological cross-reactivity between enterotoxigenic Escherichia coli heat-stable toxin and human guanylin and uroguanylin. Infect Immun. 2014;82:2913-2922. doi: 10.1128/IAI.01749-14 PMID: 24778111