Mucosal immunisation and vaccines

  • M. Fielder
  • D. J. M. Lewis
Part of the Immunology and Medicine Series book series (IMME, volume 31)


The immunisation of mucosal surfaces in mammals is vitally important to the survival of any given species. A large number of pathogenic microorganisms are first encountered at the mucosal surface. It is this first contact that may lead to the invasion and colonisation by a pathogen and the subsequent onset of disease. The gastrointestinal mucosa has a very large surface area, approximately 250 m2in the adult human (1), which can be used by microorganisms for invasion. This interaction between the microorganisms and host mucosal cells allows the scientist and the clinician an excellent field of battle for immunological priming and therefore vaccination against the invading pathogens. This approach has great potential in barring the entry to a range of bacterial, viral or protozoan pathogens before colonisation and the onset of disease. The prevention of such infections is very important both on a social and an economic scale. Rapid and relentless transmission is all too common when an infection can establish a base within the community. Fortunately, these outbreaks are decreasing in frequency in the developed world, however, in periods of human crisis or natural disaster the spectre raises its head. This has been evident in recent years with cholera outbreaks. In 1994, 45,000 people died and an estimated 600,000 were infected as a result ofVibrio cholerae01 outbreak in Rwandan refugee camps in just a three week period (2). Additionally, the need for a clean and rapid method of dispensation is also required, which is where the case for orally delivered vaccines also needs to be addressed.


Human Papilloma Virus Cholera Toxin Vaccine Strain Mucosal Immune Response Oral Immunisation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kato T, Owen RL. Structure and Function of Intestinal Mucosal epithelium. In: Ogra PL, Mestecky J, Lamm ME, Strober W, Bienenstock J, McGhee JR, editors. Mucosal Immunology. San Diego: Academic Press, 1999:115–132.Google Scholar
  2. 2.
    Waldman RJ. Cholera vaccination in refugee settings. JAMA 1998;279(7):552–553.PubMedCrossRefGoogle Scholar
  3. 3.
    Nardelli-Haefliger D, Roden RB, Benyacoub J, Sahli R, Kraehenbuhl JP, Schiller JT, Lachat P, Potts A, De Grandi P. Human papillomavirus type 16 virus-like particles expressed in attenuatedSalmonella typhimuriumelicit mucosal and systemic neutralizing antibodies in mice. Infect Immun 1997; 65: 3328–3336.PubMedGoogle Scholar
  4. 4.
    Giron JA, Xu JG, Gonzalez CR, Hone D, Kaper JB, Levine MM. Simultaneous expression of CFA/I and CS3 colonization factor antigens of enterotoxigenicEscherichia coliby delta aroC, delta aroDSalmonella typhivaccine strain CVD 908. Vaccine 1995; 13: 939–946.PubMedCrossRefGoogle Scholar
  5. 5.
    Khan CMA, Villareal-Ramos B, Pierce RJ, Demarco de Hormaeche R, McNeill H, Ali T, Chatfield S, Capron A, Dougan G, Hormaeche CE. Construction, expression and immunogenicity of theSchistosoma mansoniiP28 glutathione-S-transferase as a genetic fusion to tetanus toxin fragment C in a live Aro attenuated vaccine strain ofSalmonella.Proc Natl Acad Sci USA 1994; 91: 11261–11265.PubMedCrossRefGoogle Scholar
  6. 6.
    Gomez-Duarte OG, Lucas B, Yan ZX, Panthel K, Haas R, Meyer TF. Protection of mice against gastric colonization byHelicobacter pyloriby single oral dose immunization with attenuatedSalmonella typhimuriumproducing urease subunits A and B. Vaccine 1998;16:460–71.PubMedCrossRefGoogle Scholar
  7. 7.
    Villarreal-Ramos B, Manser J, Collins RA, Dougan G, Chatfield SN, Howard CJ. Immune responses in calves immunised orally or subcutaneously with alive Salmonella typhimuriumaro vaccine. Vaccine 1998;16:45–54.PubMedCrossRefGoogle Scholar
  8. 8.
    Dunstan SJ, Simmons CP, Strugnell RA. Comparison of the abilities of different attenuatedSalmonella typhimuriumstrains to elicit humoral immune responses against a heterologous antigen. Infect Immun 1998;66:732–40.PubMedGoogle Scholar
  9. 9.
    Clark MA, Hirst BH, Jepson MA. Inoculum composition andSalmonellapathogenicity island 1 regulate M- cell invasion and epithelial destruction bySalmonella typhimurium.Infect Immun 1998;66:724–31.PubMedGoogle Scholar
  10. 10.
    Weinstein DL, O’Neill BL, Metcalf ES.Salmonella typhistimulation of human intestinal epithelial cells induces secretion of epithelial cell-derived interleukin-6. Infect Immun 1997;65:395–404.PubMedGoogle Scholar
  11. 11.
    .Harrison JA, Villarreal-Ramos B, Mastroeni P, Demarco de Hormaeche R, Hormaeche CE. Correlates of protection induced by live Aro-Salmonella typhimuriumvaccines in the murine typhoid model. Immunology 1997;90: 618–625.PubMedCrossRefGoogle Scholar
  12. 12.
    Darji A, Guzman CA, Gerstel B, Wachholz P, Timmis KN, Wehland J, Chakraborty T, Weiss S. Oral somatic transgene vaccination using attenuatedS. typhimurium.Cell 1997;91: 765–775.PubMedCrossRefGoogle Scholar
  13. 13.
    Soo SS, Villarreal-Ramos B, Anjam Khan CM, Hormaeche CE, Blackwell JM. Genetic control of immune response to recombinant antigens carried by an attenuatedSalmonella typhimuriumvaccine strain: Nrampl influences T-helper subset responses and protection against leishmanial challenge. Infect Immun 1998 May;66:1910–1917.PubMedGoogle Scholar
  14. 14.
    Gonzalez CR, Noriega FR, Huerta S, Santiago A, Vega M, Paniagua J, Ortiz-Navarrete V, Isibasi A, Levine MM. Immunogenicity ofa Salmonella typhiCVD 908 candidate vaccine strain expressing the major surface protein gp63 ofLeishmania mexicana mexicana.Vaccine 1998;16:1043–1052.PubMedCrossRefGoogle Scholar
  15. 15.
    Xu D, McSorley SJ, Chatfield SN, Dougan G, Liew FY. Protection againstLeishmania majorinfection in genetically susceptible BALB/c mice by gp63 delivered orally in attenuatedSalmonella typhimurium(AroA-AroD-). Immunology. 1995; 85: 1–7.PubMedGoogle Scholar
  16. 16.
    Stager S, Gottstein B, Muller N. Systemic and local antibody response in mice induced by a recombinant peptide fragment fromGiardia lambliavariant surface protein (VSP) H7 produced bya Salmonella typhimuriumvaccine strain. Int J Parasitol 1997;27:965–71.PubMedCrossRefGoogle Scholar
  17. 17.
    Attridge SR, Davies R, LaBrooy JT. Oral delivery of foreign antigens by attenuatedSalmonella:consequences of prior exposure to the vector strain. Vaccine 1997; 15: 155–162.PubMedCrossRefGoogle Scholar
  18. 18.
    Dougan G, Hormaeche CE, Maskell DJ. Live oralSalmonellavaccines: potential use of attenuated strains as carriers of heterologous antigens to the immune system. Parasite Immun 1987; 9: 151–160.Google Scholar
  19. 19.
    Chaicumpa W, Chongsa-nguan M, Kalambaheti T, Wilairatana P, Srimanote P, Makakunkijcharoen Y, Looareesuwan S, Sakolvaree Y. Immunogenicity of liposome-associated and refined antigen oral cholera vaccines in Thai volunteers. Vaccine 1998;16: 678–684.PubMedCrossRefGoogle Scholar
  20. 20.
    Kimsey HH, Waldor MK. CTXphi immunity: application in the development of cholera vaccines. Proc Natl Acad Sci USA 1998; 95: 7035–7039.PubMedCrossRefGoogle Scholar
  21. 21.
    Taylor DN, Tacket CO, Losonsky G, Castro O, Gutierrez J, Meza R, Nataro JP, Kaper JB, Wasserman SS, Edelman R, Levine MM, Cryz SJ. Evaluation of a bivalent (CVD 103-HgR/CVD 111) live oral cholera vaccine in adult volunteers from the United States and Peru. Infect Immun 1997;65:3852–3856.PubMedGoogle Scholar
  22. 22.
    Tacket CO, Kotloff KL, Losonsky G, et al. Volunteer studies investigating the safety and efficacy of live oral El Tor Vibrio cholerae 01 vaccine strain CVD 111. Am J Trop Med Hyg 1997;56(5):533–7.PubMedGoogle Scholar
  23. 23.
    Cedre Marrero B, Garcia Imia LG, Garcia Sanchez HM, Farinas Medina M, Talavera Coronel A, Infante Bourzac JF. Intestinal colonization of the infant mouse model by attenuated and virulentVibrio choleraestrains. Arch Med Res. 1998; 29: 231–234.PubMedGoogle Scholar
  24. 24.
    Cohen MB, Giannella RA, Losonsky GA, Lang DR, Parker S, Hawkins JA, Gunther C, Schiff GA. Validation and characterization of a human volunteer challenge model for cholera by using frozen bacteria of the newVibrio choleraeepidemic serotype, 0139. Infect Immun 1999; 67: 6346–9.PubMedGoogle Scholar
  25. 25.
    Tacket CO, Cohen MB, Wasserman SS, Losonsky G, Livio S, Kotloff K, Edelman R, Kaper JB, Cryz SJ, Giannella RA, Schiff G, Levine MM. Randomized, double-blind, placebo-controlled, multicentered trial of the efficacy of a single dose of live oral cholera vaccine CVD 103-HgR in preventing cholera following challenge withVibrio cholerae01 El tor inaba three months after vaccination. Infect Immun 1999;67: 6341–6345.PubMedGoogle Scholar
  26. 26.
    Ahrén C, Jertborn M, Svennerholm A. Intestinal immune responses to an inactivated oral enterotoxigenicEscherichia colivaccine and associated immunoglobulin A responses in blood. Infection and Immunity 1998;66:3311–3316.PubMedGoogle Scholar
  27. 27.
    Tackett CO, Mason HS, Losonsky G, Clements JD, Levine MM, Arntzen CJ. Immunogenicity in humans of a recombinant bacterial antigen delivered in a transgenic potato. Nature Med. 1998;4: 607–609.CrossRefGoogle Scholar
  28. 28.
    Arakawa T, Chong DKX, Langridge WHR. Eficacy of a food plant-based oral cholera toxin B subunit vaccine. Nature Biotech 1997; 16: 292–297.CrossRefGoogle Scholar
  29. 29.
    Konadu E, Donohue-Rolfe A, Calderwood SB, Pozsgay V, Shiloach J, Robbins JB, Szu SC. Syntheses and immunologic properties ofEscherichia coli0157 0-specific polysaccharide and Shiga toxin 1 B subunit conjugates in mice. Infect Immun 1999; 67: 6191–6193.PubMedGoogle Scholar
  30. 30.
    Konadu EY, Parke JC Jr, Tran HT, Bryla DA, Robbins JB, Szu SC. Investigational vaccine forEscherichia coli0157: phase 1 study of 0157 O-specific polysaccharide-Pseudomonasaeruginosarecombinant exoprotein A conjugates in adults. J Infect Dis 1998;177: 383–387.PubMedCrossRefGoogle Scholar
  31. 31.
    Conlan JW, Cox AD, KuoLee R, Webb A, Perry MB. Parenteral immunization with a glycoconjugate vaccine containing the 0157 antigen ofEscherichia coliO157:H7 elicits a systemic humoral immune response in mice, but fails to prevent colonization by the pathogen. Can J Microbiol 1999; 45: 279–286.PubMedGoogle Scholar
  32. 32.
    Dunn BE, Cohen H, Blaser MJ.Helicobacter pylori.Clin Rev Microbiol 1997;10: 720–741.Google Scholar
  33. 33.
    Radcliff FJ, Hazell SL, Kolesnikow T, Doidge C, Lee A. Catalase, a novel antigen forHelicobacter pylorivaccination. Infect Immun 1997; 65: 4668–4674.PubMedGoogle Scholar
  34. 34.
    Kleanthous H, Myers GA, Georgakopoulos KM Tibbitts TJ, Ingrassia JW, Gray HL, Ding R, Zhang ZZ, Lei W, Nichols R, Lee CK, Ermak TH, Monath TP. Rectal and intranasal immunizations with recombinant urease induce distinct local and serum immune responses in mice and protect againstHelicobacter pyloriinfection. Infect Immun 1998;66: 2879–2886.PubMedGoogle Scholar
  35. 35.
    Corthesy-Theulaz IE, Hopkins S, Bachmann D, Saldinger PF, Porta N, Haas R, Zheng-Xin Y, Meyer T, Bouzourene H, Blum AL, Kraehenbuhl JP. Mice are protected fromHelicobacter pyloriinfection by nasal immunization with attenuated Salmonella typhimurium phoPc expressing urease A and B subunits. Infect Immun 1998;66: 581–586.PubMedGoogle Scholar
  36. 36.
    Ghiara P, Rossi M, Marchetti M, Di Tommaso A, Vindigni C, Ciampolini F, Covacci A, Telford JL, De Magistris MT, Pizza M, Rappuoli R, Del Giudice G. Therapeutic intragastric vaccination againstHelicobacter pylori inmice eradicates and otherwise chronic infection and confers protection against reinfection. Infect Immun. 1997;65: 4996–5002.PubMedGoogle Scholar
  37. 37.
    Marchetti M, Rossi M, Giannelli V, Giuliani MM, Pizza M, Censini S, Covacci A, Massari P, Pagliaccia C, Manetti R, Telford JL, Douce G, Dougan G, Rappuoli R, Ghiara P. Protection againstHelicobacter pyloriinfection in mice by intragastric vaccination withH. pyloriantigens is achieved using a non-toxic mutant ofE. coliheat-labile enterotoxin (LT) as adjuvant. Vaccine 1998;16: 33–37.PubMedCrossRefGoogle Scholar
  38. 38.
    Ikewaki J, Nishizono A, Goto T, Fujioka T, Mifune K. Therapeutic oral vaccination induces mucosal immune response sufficient to eliminate longtermHelicobacter pyloriinfection. Microbiol Immunol 2000; 44: 29–39.PubMedGoogle Scholar
  39. 39.
    Lazowska I, Trzeciak L, Godlewska R, Hennig E, Jagusztyn-Krynicka K, Popowski J, Regula J, Ostrowski J. In search of immunogenicHelicobacter pyloriproteins by screening of expression library. Digestion. 2000;61: 14–21.PubMedCrossRefGoogle Scholar
  40. 40.
    Klee SR, Tzschaschel BD, Singh M, Fait I, Lindberg AA, Timmis KN, Guzman CA. Construction and characterization of genetically-marked bivalent anti-Shigella dysenterae1 andanti-Shigella flexneriY live vaccine candidates. Microb Pathog 1997;22(6):363–76.PubMedCrossRefGoogle Scholar
  41. 41.
    Klee SR, Tzschaschel BD, Falt I, Karnell A, Lindberg AA, Timmis KN, Guzman CA. Construction and characterization of a live attenuated vaccine candidate againstShigella dysenteriaetype].Infect Immun. 1997 Jun;65: 2112–2118.Google Scholar
  42. 42.
    Hartman AB, Van De Verg LL, Venkatesan MM. Native and mutant forms of cholera toxin and heat-labile enterotoxin effectively enhance protective efficacy of live attenuated and heat-killedShigellavaccines. Infect Immun 1999;67(11):5841–5847.PubMedGoogle Scholar
  43. 43.
    De Magistris MT, Pizza M, Douce G, Ghiara P, Dougan G, Rappuoli R. Adjuvant effect of non-toxic mutants ofE. coliheat-labile enterotoxin following intranasal, oral and intravaginal immunization. Dev Biol Stand 1998;92:123–126.PubMedGoogle Scholar
  44. 44.
    Giuliani MM, Del Giudice G, Giannelli V, Dougan G, Douce G, Rappuoli R, Pizza M. Mucosal adjuvanticity and immunogenicity of LTR72, a novel mutant of Escherichia coli heat-labile enterotoxin with partial knockout of ADP- ribosyltransferase activity. J Exp Med 1998;187:1123–1132.PubMedCrossRefGoogle Scholar
  45. 45.
    Chong C, Friberg M, Clements JD. LT(R192G), a non-toxic mutant of the heat-labile enterotoxin ofEscherichia coli, elicits enhanced humoral and cellular immune responses associated with protection against lethal oral challenge withSalmonellaspp. Vaccine 1998;16: 732–740.PubMedCrossRefGoogle Scholar
  46. 46.
    Yamamoto S, Kiyono H, Yamamoto M, Imaoka K, Fujihashi K, Van Ginkel FW, Noda M, Takeda Y, McGhee JR. A nontoxic mutant of cholera toxin elicits Th2-type responses for enhanced mucosal immunity. Proc Natl Acad Sci U S A 1997; 94: 5267–5272.PubMedCrossRefGoogle Scholar
  47. 47.
    Covone MG, Brocchi M, Palla E, Dias da Silveira W, Rappuoli R, Galeotti CL. Levels of expression and immunogenicity of attenuatedSalmonella entericaserovar typhimurium strains expressingEscherichia colimutant heat-labile enterotoxin. Infect Immun 1998; 66: 224–231.PubMedGoogle Scholar
  48. 48.
    Douce G, Giannelli V, Pizza M, Lewis D, Everest P, Rappuoli R, Dougan G. Genetically detoxified mutants of heat-labile toxin from Escherichia coli are able to act as oral adjuvants. Infect Immun. 1999;67:4400–4406.PubMedGoogle Scholar
  49. 49.
    Hayward CM, O’Gaora P, Young DB, Griffin GE, Thole J, Hirst TR, Castello-Branco LR, Lewis DJM. Construction and murine immunogenicity of recombinant Bacille Calmette Guerin vaccines expressing the B subunit ofEscherichia coliheat labile enterotoxin. Vaccine 1999 5;17: 1272–1281CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • M. Fielder
  • D. J. M. Lewis

There are no affiliations available

Personalised recommendations