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Expert Review of Vaccines Volume 2, 2003 - Issue 2
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Review

Mutants of the Escherichia coli heat-labile enterotoxin as safe and strong adjuvants for intranasal delivery of vaccines

Samuele Peppoloni IRIS Research Center, Department of Hygiene, Microbiology and Biostatistical Sciences, University of Modena and Reggio Emilia, Via Campi 287, 14100 Modena, Italy
,
Paolo Ruggiero IRIS Research Center, Department of Hygiene, Microbiology and Biostatistical Sciences, University of Modena and Reggio Emilia, Via Campi 287, 14100 Modena, Italy
,
Mario Contorni IRIS Research Center, Department of Hygiene, Microbiology and Biostatistical Sciences, University of Modena and Reggio Emilia, Via Campi 287, 14100 Modena, Italy
,
Maurizio Morandi IRIS Research Center, Department of Hygiene, Microbiology and Biostatistical Sciences, University of Modena and Reggio Emilia, Via Campi 287, 14100 Modena, Italy
,
Mariagrazia Pizza IRIS Research Center, Department of Hygiene, Microbiology and Biostatistical Sciences, University of Modena and Reggio Emilia, Via Campi 287, 14100 Modena, Italy
,
Rino Rappuoli IRIS Research Center, Department of Hygiene, Microbiology and Biostatistical Sciences, University of Modena and Reggio Emilia, Via Campi 287, 14100 Modena, Italy
,
Audino Podda IRIS Research Center, Department of Hygiene, Microbiology and Biostatistical Sciences, University of Modena and Reggio Emilia, Via Campi 287, 14100 Modena, Italy
&
Giuseppe Del Giudice IRIS Research Center, Department of Hygiene, Microbiology and Biostatistical Sciences, University of Modena and Reggio Emilia, Via Campi 287, 14100 Modena, Italy
 show all
Pages 285-293 | Published online: 09 Jan 2014

References

  • Rappuoli R, Pizza M, Douce G, Dougan G. Structure and mucosal adjuvanticity of cholera and Escherichia coil heat-labile enterotoxins. Immune'. Today 20, 493–500 (1999).
  • Braun MC, He J, Wu CY, Kelsall BL. Cholera toxin suppresses interleukin (IL) -12 production and IL-12 receptor 01 and 02 chain expression. I Exp. Merl 189, 541–552 (1999).
  • Takahashi I, Marinaro M, Kimono H et al. Mechanisms of mucosal immunogenicity and adjuvancy of Escherichia coil labile enterotoxin. j Infect. Dis. 173, 627–635(1996).
  • Yamamoto M, Kiyono H, Kweon MN et al. Enterotoxin adjuvants have direct effects on T-cells and antigen-presenting cells that result in either interleukin-4-dependent or -independent immune responses. J. Infect. Dis. 182,180-190 (2000).
  • Bowman CC, Clements JD. Differential biological and adjuvant activities of cholera toxin and Escherichia coil heat-labile enterotoxin hybrids. Infect. Immun. 69,1528–1535 (2001).
  • Wilson AD, Robinson A, Irons L, Stokes CR. Adjuvant action of cholera toxin and pertussis toxin in the induction of IgA antibody response to orally administered antigens. Vaccine 11, 113–118 (1993).
  • Burnette WN, Mar VL, Platler BW et al. Site-specific mutagenesis of the catalytic subunit of cholera toxin: substituting lysine for arginine 7 causes loss of activity. Infect. Immun. 59, 4266–4270 (1991).
  • Jobling MG, Holmes RK. Analysis of structure and function of the B subunit of cholera toxin by the use of site-directed mutagenesis. Mol Mcrobiol 5, 1755–1767 (1991).
  • Domenighini M, Magagnoli C, Pizza M, Rappuoli R. Common features of the NAD-binding and catalytic site of ADP-ribosylating toxins. Mal Microbial 14, 41–50 (1994).
  • Dickinson DL, Clements JD. Dissociation of Escherichia cob heat-labile enterotoxin adjuvanticity from ADP-ribosyltransferase activity. Infect. 'minim. 63, 1617–1623 (1995).
  • Giannelli V, Fontana MR, Giuliani MM, Guancgai D, Rappuoli R, Pizza M. Protease susceptibility and toxicity of heat-labile enterotoxins with a mutation in the active site or in the protease-sensitive loop. Infect. Immun. 65, 331–334 (1997).
  • Douce G, Turcotte C, Cropley I et al. Mutants of Escherichia coil heat-labile toxin lacking ADP-ribosyltransferase activity act as nontoxic, mucosal adjuvants. Proc. Nat! Acad. Sci USA 92, 1644–1648 (1995).
  • Giuliani MM, Del Giudice G, Giannelli V et al. Mucosal adjuvanticity and immunogenicity of LTR72, a novel mutant of Escherichia cob heat-labile enterotoxin with partial knockout of ADP-ribosyltransferase activity. I Exp. Med 187, 1123–1132 (1998).
  • Lycke N, Tsuji T, Holmgren J. The adjuvant effect of Vibrio cholerae and Escherichia con heat-labile enterotoxins is linked to their ADP—ribosyltransferase activity. Eur. j Immunol 22, 2277–2281 (1992).
  • Pizza M, Domenighini M, Hol W et al. Probing the structure-activity relationship of Escherichia cob LT-A by site-directed mutagenesis. Mal Mcrobiol 14, 51–60 (1994).
  • Pizza M, Fontana MR, Giuliani MM et al. A genetically detoxified derivative of heat-labile E. co/ienterotoxin induces neutralizing antibodies against the A subunit. j Exp. Med 180, 2147–2153 (1994).
  • de Haan L, Verweij VVR, Feil IK et al. Mutants of Escherichia cob heat-labile enterotoxin with reduced ADP-ribosylation activity or no activity retain the immunogenic properties of the native holotoxin. Infect. Immun. 64, 5413–5416 (1996).
  • Douce G, Giuliani MM, Giannelli V, Pizza M, Rappuoli R, Dougan G. Mucosal immunogenicity of genetically detoxified derivatives of heat labile toxin from Escherichia coll. Vaccine 16,1065–1073 (1998).
  • Kato M, Imamura S, Kawase H, Miyama A, Tsuji T Histidine-44 of the A subunit of Escherichia cob enterotoxin is involved in its enzymatic and biological activities. FEMS Mcrobiol Lett. 152, 219–225 (1997).
  • Douce G,Giannelli V, Pizza M et al. Genetically detoxified mutants of heat-labile toxin from Escherichia cob are able to act as oral adjuvants. Infect. Immun. 67, 4400–4406 (1999).
  • Ryan EJ, McNeela E, Murphy GA et al. Mutants of Escherichia wil heat-labile toxin act as effective mucosal adjuvants for nasal delivery of an acellular pertussis vaccine: differential effects of the nontoxic AB complex and enzyme activity on Thl and Th2 cells. Infect. Immun. 67, 6270–6280 (1999).
  • Partidos CD, Salani BF, Pizza M, Rappuoli R. Heat-labile enterotoxin of Escherichia cob and its site-directed mutant LTK63 enhance the proliferative and cytotoxic T-cell responses to intranasally co-immunized synthetic peptides. Immunol Lett. 67, 209–216 (1999).
  • •Ability of LT mutants to induce vaccine-specific CD8+ cells.
  • Marinaro M, Staats HF, Hiroi T et al. Mucosal adjuvant effect of cholera toxin in mice results from induction of T-helper 2 (Th2) cells and IL-4. I Immunol 155, 4621–4629 (1995).
  • Ryan EJ, McNeela E, Pizza M, Rappuoli R, O'Neil L, Mills KH. Modulation of innate and acquired immune response by Escherichia cob heat-labile toxin: distinct pro- and anti-inflammatory effects of the nontoxic AB complex and the enzyme activity. I Immuno1165, 5750–5759 (2000).
  • •Functional T-cell subset activation by LT muatants.
  • Del Giudice G, Covacci A, Telford JL, Montecucco C, Rappuoli R. The design of vaccines against Helicobacter pylori and their development. Ann. Rev Immunol 19, 523–563 (2001).
  • Koprowski IIH, Levine MM, Anderson RJ, Losonsky G, Pizza M, Barry EM. Attenuated Shigella Ilexneri 2a vaccine strain CVD 1204 expressing colonization factor antigen I and mutant heat-labile enterotoxin of enterotoxigenic Escherichia cob. Infect. 'minim. 68,4884-4892 (2000).
  • Scharton-Kersten T, Yu JM, Vassell R, O'Hagan D, Alving CR, Glenn GM. Transcutaneous immunization with bacterial ADP-ribosylating exotoxins, subunits and unrelated adjuvants. Infect. Immun. 68, 5306–5313 (2000).
  • Ugozzoli M, Santos G, Donnelly J, O'Hagan DT Potency of a genetically detoxified mucosal adjuvant derived from the heat-labile enterotoxin of Escherichia coli (LTK63) is not adversely affected by the presence of preexisting immunity to the adjuvant. Infect. DiS 183, 351–354 (2001).
  • Yuan L, Geyer A, Hodgins DC et al. Intranasal administration of 2/6-rotavirus-like particles with mutant Escherichia cob heat-labile toxin (LT-R192G) induces antibody-secreting cell responses but not protective immunity in gnotobiotic pigs. Virol. 74, 8843–8853 (2000).
  • Greer CE, Petracca R, Buonamassa DT et al The comparison of the effect of LTR72 and NE59 adjuvants on mouse humoral response to intranasal immunisation with human papillomavirus Type 6b (HPV-6b) virus-like particles. Vaccine 19, 1008–1012 (2000).
  • Simmons CP, Hussel T, Sparer T, Walzl G, Openshaw P, Dougan G. Mucosal delivery of a respiratory syncytial virus CTL peptide with enterotoxin-based adjuvants elicits protective, immunopathogenic and immunoregulatory antiviral CD8* T-cell responses. j Immunol 166, 1106–1113 (2001).
  • ••Ability of LT mutants to induce vaccine-specific CD8+ cells.
  • Barackman JD, Ott G, O'Hagan DT Intranasal immunization of mice with influenza vaccine in combination with the adjuvant LT-R72 induces potent mucosal and serum immunity, which is stronger than that with traditional intramuscular immunization. Infect. IMMU17. 67, 4276–4279 (1999).
  • Hagiwar Y, Tsuji T, Iwasaki T et al Effectiveness and safety of mutant Escherichia coil heat-labile enterotoxin (LT H44A) as an adjuvant for nasal influenza vaccine. Vaccine 19, 2071–2079 (2001).
  • Jakobsen H, Bjarnarson S, Del Giudice G, Moreau M, Siegrist CA, Jonsdottir I. Intranasal immunization with pneumococcal conjugate vaccines with LTK63, a nontoxic mutant of heat-labile enterotoxin, as adjuvant rapidly induces protective immunity against lethal pneumococcal infections in neonatal mice. Infect. Immun. 70,1443-1452 (2002).
  • •Adjuvanticity of LTK63 in neonates.
  • Bonenfant C, Bimier-Poisson I, Velge-Roussel F et al. Intranasal immunization with SAG 1 and nontoxic mutant heat-labile enterotoxins protects mice against Toxoplasma gondiL Infect. Immun. 69, 1605–1612 (2001).
  • Singh M, Briones M, O'Hagan DT A novel bioadhesive intranasal delivery system for inactivated influenza vaccines. Control. Release 70,267–276 (2001).
  • Baudner BC, Balland O, Giuliani MM et al. Enhancement of protective efficacy following intranasal immunization with vaccine plus a nontoxic LTK63 mutant delivered with nanoparticles. Infect. Immun. 70,4785-4790 (2002).
  • •Additive effect of LT1(63 and bioadhesive material after intranasal immunization.
  • Ricciardi-Castagnoli P, Granucci E Interpretation of the complexity of innate immune responses by functional genomics. Nat. Rev Immunol 2,881–889 (2002).
  • Pizza M, Giuliani MM, Fontana MT et al. Mucosal vaccines: non-toxic derivatives of LT and CT as mucosal adjuvants. Vaccine21, 2534–2541 (2001).
  • Clack U, Gebbers JO, Gluck R. Phase 1 evaluation of intranasal virosomal influenza vaccine with and without Escherichia cob heat-labile toxin in adult volunteers. j Vim'. 73,7780-7786 (1999).
  • Clack R, Mischler R, Durrer P et al. Safety and immunogenicity of intranasally administered inactivated trivalent virosome-formulated influenza vaccine containing Escherichia cob heat-labile toxin as a mucosal adjuvant. j Infect. Dis. 181, 1129–1132 (2000).
  • Michetti P, Kreiss C, Kotloff KL et al. Oral immunization with urease and Escherichia cob heat-labile enterotoxin is safe and immunogenic in Helicobacter pylori-infected adults. Gastroenterology116, 804–812 (1999).
  • van Ginkel FVV, Jackson RJ, Yuki Y, McGhee JR. The mucosal adjuvant cholera toxin redirects vaccine proteins into olfactory tissues. J Immunol 165, 4778–4782 (2000).
  • Cheng E, Cardenas-Freytag L, Clements JD. The role of cAMP in mucosal adjuvanticity of Escherichia cob heat-labile enterotoxin (LT). Vaccine 18,38–49 (1999).
  • Bisteau M, Abarca J, Bourguignon P, Hermand P, Francotte M. Intranasal administration of enterotoxins induces reactogenicity in the brain of different mice strains. Euroconference Workshop, Novel Strategies of Mucosa' Immunization through Exploitation of Mechanisms of Innate Immunity in Pathogen-Host Interaction, Siena, Italy 6–10,80 (2002).
  • Simecka RV, Jackson RJ, Kiyono H, McGhee JR. Mucosally induced immunoglobulin E — associated inflammation in the respiratory tract. Infect. Immun. 68,672–679 (2000).
  • Kotloff K, Sztein MB, Wasserman SS, Losonsky GA, DiLorenzo SC, Walker R. Safety and immunogenicity of oral inactivated whole-cell Helicobacter pylori vaccine with adjuvant among volunteers with or without subclinical infection. Infect. Immun. 69,3581–3590 (2001).

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