Skip to main content
SpringerLink
Log in

Oral Vaccination: Attenuated and Gene-Based

  • Chapter
  • First Online:
Book cover Novel Immune Potentiators and Delivery Technologies for Next Generation Vaccines

  • 1192 Accesses

Abstract

The ability to deliver vaccines by a pill, capsule, chewable candy, or even as a liquid slurry represents a delivery improvement over injected vaccines. Besides the pain of watching our young children return from the pediatrician with multiple band-aids on their legs and tears in the eyes, vaccines that can be administered in the absence of needles have several advantages. Distribution and manufacturing are greatly simplified. A pill can be handed out by anyone, not necessarily by qualified medical support. No sterile filling of syringes or vials is necessary because the stomach and intestinal track handle non-sterile food all the time. Unwanted needle sticks and sharps disposal are avoided. From a performance improvement standpoint, delivering a vaccine mucosally could improve the immune responses mucosally since 90 % of pathogens invade by this route and parenteral delivery is not particularly adept at inducing immunity at a mucosal surface. Several approved oral vaccines have been developed, and several oral platform approaches are under investigation that might expand the available pool of vaccines. This chapter reviews the history of oral vaccines, both approved and vaccines in early stages of development.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bodian D (1949) Neutralization of three immunological types of poliomyelitis virus by human gamma globulin. Proc Soc Exp Biol Med 72:259–261

    PubMed  CAS  Google Scholar 

  2. WHO (2010) Performance of acute flaccid paralysis (AFP) surveillance and incidence of poliomyelitis, 2010 (data received in WHO headquarters as of June 1 2010). Wkly Epidemiol Rec 85:244–247

    Google Scholar 

  3. Wassilak S, Orenstein W (2010) Challenges faced by the global polio eradication initiative. Expert Rev Vaccines 9:447–449

    Article  PubMed  Google Scholar 

  4. CDC (2010) Progress toward poliomyelitis eradication—India, January 2009–October 2010. MMWR Morb Mortal Wkly Rep 59:1581–1585

    Google Scholar 

  5. Fine PE (2009) Polio: measuring the protection that matters most. J Infect Dis 200:673–675

    Article  PubMed  Google Scholar 

  6. Grassly NC, Jafari H, Bahl S, Durrani S, Wenger J, Sutter RW, Aylward RB (2009) Mucosal immunity after vaccination with monovalent and trivalent oral poliovirus vaccine in India. J Infect Dis 200:794–801

    Article  PubMed  Google Scholar 

  7. Kew O, Morris-Glasgow V, Landaverde M, Burns C, Shaw J, Garib Z, Andre J, Blackman E, Freeman CJ, Jorba J, Sutter R, Tambini G, Venczel L, Pedreira C, Laender F, Shimizu H, Yoneyama T, Miyamura T, van Der Avoort H, Oberste MS, Kilpatrick D, Cochi S, Pallansch M, de Quadros C (2002) Outbreak of poliomyelitis in Hispaniola associated with circulating type 1 vaccine-derived poliovirus. Science 296:356–359

    Article  PubMed  CAS  Google Scholar 

  8. Alexander JP, Ehresmann K, Seward J, Wax G, Harriman K, Fuller S, Cebelinski EA, Chen Q, Jorba J, Kew OM, Pallansch MA, Oberste MS, Schleiss M, Davis JP, Warshawsky B, Squires S, Hull HF (2009) Transmission of imported vaccine-derived poliovirus in an undervaccinated community in Minnesota. J Infect Dis 199:391–397

    Article  PubMed  Google Scholar 

  9. Santos N, Hoshino Y (2005) Global distribution of rotavirus serotypes/genotypes and its implication for the development and implementation of an effective rotavirus vaccine. Rev Med Virol 15:29–56

    Article  PubMed  Google Scholar 

  10. Parashar UD, Bresee JS, Gentsch JR, Glass RI (1998) Rotavirus. Emerg Infect Dis 4:561–570

    Article  PubMed  CAS  Google Scholar 

  11. Parashar UD, Burton A, Lanata C, Boschi-Pinto C, Shibuya K, Steele D, Birmingham M, Glass RI (2009) Global mortality associated with rotavirus disease among children in 2004. J Infect Dis 200(Suppl 1):S9–S15

    Article  PubMed  Google Scholar 

  12. CDC (2011) Rotavirus surveillance—worldwide, 2009. Morb Mortal Wkly Rep 60:514–516

    Google Scholar 

  13. WHO (2009) Rotavirus Vaccines: an update. Wkly Epidemiol Rec 84:533–540

    Article  PubMed  Google Scholar 

  14. Yen C, Armero Guardado JA, Alberto P, Rodriguez Araujo DS, Mena C, Cuellar E, Nolasco JB, De Oliveira LH, Pastor D, Tate JE, Parashar UD, Patel MM (2011) Decline in rotavirus hospitalizations and health care visits for childhood diarrhea following rotavirus vaccination in El Salvador. Pediatr Infect Dis J 30:S6–S10

    Article  PubMed  Google Scholar 

  15. Tate JE, Mutuc JD, Panozzo CA, Payne DC, Cortese MM, Cortes JE, Yen C, Esposito DH, Lopman BA, Patel MM, Parashar UD (2011) Sustained decline in rotavirus detections in the United States following the introduction of rotavirus vaccine in 2006. Pediatr Infect Dis J 30:S30–S34

    Article  PubMed  Google Scholar 

  16. Quintanar-Solares M, Yen C, Richardson V, Esparza-Aguilar M, Parashar UD, Patel MM (2011) Impact of rotavirus vaccination on diarrhea-related hospitalizations among children <5 years of age in Mexico. Pediatr Infect Dis J 30:S11–S15

    Article  PubMed  Google Scholar 

  17. Buttery JP, Lambert SB, Grimwood K, Nissen MD, Field EJ, Macartney KK, Akikusa JD, Kelly JJ, Kirkwood CD (2011) Reduction in rotavirus-associated acute gastroenteritis following introduction of rotavirus vaccine into Australia’s National Childhood vaccine schedule. Pediatr Infect Dis J 30:S25–S29

    Article  PubMed  Google Scholar 

  18. Joensuu J, Koskenniemi E, Pang XL, Vesikari T (1997) Randomised placebo-controlled trial of rhesus-human reassortant rotavirus vaccine for prevention of severe rotavirus gastroenteritis. Lancet 350:1205–1209

    Article  PubMed  CAS  Google Scholar 

  19. Perez-Schael I, Guntinas MJ, Perez M, Pagone V, Rojas AM, Gonzalez R, Cunto W, Hoshino Y, Kapikian AZ (1997) Efficacy of the rhesus rotavirus-based quadrivalent vaccine in infants and young children in Venezuela. N Engl J Med 337:1181–1187

    Article  PubMed  CAS  Google Scholar 

  20. Rennels MB, Glass RI, Dennehy PH, Bernstein DI, Pichichero ME, Zito ET, Mack ME, Davidson BL, Kapikian AZ (1996) Safety and efficacy of high-dose rhesus-human ­reassortant rotavirus vaccines—report of the National Multicenter Trial. United States Rotavirus Vaccine Efficacy Group. Pediatrics 97:7–13

    PubMed  CAS  Google Scholar 

  21. Santosham M, Moulton LH, Reid R, Croll J, Weatherholt R, Ward R, Forro J, Zito E, Mack M, Brenneman G, Davidson BL (1997) Efficacy and safety of high-dose rhesus-human ­reassortant rotavirus vaccine in Native American populations. J Pediatr 131:632–638

    Article  PubMed  CAS  Google Scholar 

  22. CDC (1999) Withdrawal of rotavirus vaccine recommendation. Morb Mortal Wkly Rep 43:1007

    Google Scholar 

  23. Bines JE (2005) Rotavirus vaccines and intussusception risk. Curr Opin Gastroenterol 21:20–25

    PubMed  Google Scholar 

  24. Vesikari T, Clark HF, Offit PA, Dallas MJ, DiStefano DJ, Goveia MG, Ward RL, Schodel F, Karvonen A, Drummond JE, DiNubile MJ, Heaton PM (2006) Effects of the potency and composition of the multivalent human-bovine (WC3) reassortant rotavirus vaccine on efficacy, safety and immunogenicity in healthy infants. Vaccine 24:4821–4829

    Article  PubMed  CAS  Google Scholar 

  25. Linhares AC, Ruiz-Palacios GM, Guerrero ML, Salinas B, Perez-Schael I, Clemens SA, Innis B, Yarzabal JP, Vespa G, Cervantes Y, Hardt K, De Vos B (2006) A short report on highlights of world-wide development of RIX4414: a Latin American experience. Vaccine 24:3784–3785

    Article  PubMed  CAS  Google Scholar 

  26. Salinas B, Perez Schael I, Linhares AC, Ruiz Palacios GM, Guerrero ML, Yarzabal JP, Cervantes Y, Costa Clemens S, Damaso S, Hardt K, De Vos B (2005) Evaluation of safety, immunogenicity and efficacy of an attenuated rotavirus vaccine, RIX4414: a randomized, placebo-controlled trial in Latin American infants. Pediatr Infect Dis J 24:807–816

    Article  PubMed  Google Scholar 

  27. Ruiz-Palacios GM, Perez-Schael I, Velazquez FR, Abate H, Breuer T, Clemens SC, Cheuvart B, Espinoza F, Gillard P, Innis BL, Cervantes Y, Linhares AC, Lopez P, Macias-Parra M, Ortega-Barria E, Richardson V, Rivera-Medina DM, Rivera L, Salinas B, Pavia-Ruz N, Salmeron J, Ruttimann R, Tinoco JC, Rubio P, Nunez E, Guerrero ML, Yarzabal JP, Damaso S, Tornieporth N, Saez-Llorens X, Vergara RF, Vesikari T, Bouckenooghe A, Clemens R, De Vos B, O’Ryan M (2006) Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med 354:11–22

    Article  PubMed  CAS  Google Scholar 

  28. WHO (2011) Meeting of the Global Advisory Committee on vaccine safety, Dec 2010. Wkly Epidemiol Rec 86:37–44

    Google Scholar 

  29. Madhi SA, Cunliffe NA, Steele D, Witte D, Kirsten M, Louw C, Ngwira B, Victor JC, Gillard PH, Cheuvart BB, Han HH, Neuzil KM (2010) Effect of human rotavirus vaccine on severe diarrhea in African infants. N Engl J Med 362:289–298

    Article  PubMed  CAS  Google Scholar 

  30. Fu C, Wang M, Liang J, He T, Wang D, Xu J (2007) Effectiveness of Lanzhou lamb rotavirus vaccine against rotavirus gastroenteritis requiring hospitalization: a matched case–control study. Vaccine 25:8756–8761

    Article  PubMed  CAS  Google Scholar 

  31. Ryan ET, Calderwood SB (2000) Cholera vaccines. Clin Infect Dis 31:561–565

    Article  PubMed  CAS  Google Scholar 

  32. Steinberg E, Greene D, Bopp C, Cameron D, Wells J, Mintz E (2001) Cholera in the United states, 1995–2000: trends at the end of the twentieth century. J Infect Dis 184:799–802

    Article  PubMed  CAS  Google Scholar 

  33. WHO (2007) Cholera, 2006. Wkly Epidemiol Rec 82:273–284

    Google Scholar 

  34. Clemens JD, Sack DA, Harris JR, Chakraborty J, Khan MR, Stanton BF, Kay BA, Khan MU, Yunus M, Atkinson W et al (1986) Field trial of oral cholera vaccines in Bangladesh. Lancet 2:124–127

    Article  PubMed  CAS  Google Scholar 

  35. Sanchez JL, Vasquez B, Begue RE, Meza R, Castellares G, Cabezas C, Watts DM, Svennerholm AM, Sadoff JC, Taylor DN (1994) Protective efficacy of oral whole-cell/recombinant-B-subunit cholera vaccine in Peruvian military recruits. Lancet 344:1273–1276

    Article  PubMed  CAS  Google Scholar 

  36. Clemens JD, Sack DA, Harris JR, Van Loon F, Chakraborty J, Ahmed F, Rao MR, Khan MR, Yunus M, Huda N et al (1990) Field trial of oral cholera vaccines in Bangladesh: results from three-year follow-up. Lancet 335:270–273

    Article  PubMed  CAS  Google Scholar 

  37. Epaulard O, Derouazi M, Margerit C, Marlu R, Filopon D, Polack B, Toussaint B (2008) Optimization of a type III secretion system-based Pseudomonas aeruginosa live vector for antigen delivery. Clin Vaccine Immunol 15:308–313

    Article  PubMed  CAS  Google Scholar 

  38. Germanier R, Fuer E (1975) Isolation and characterization of Gal E mutant Ty 21a of Salmonella typhi: a candidate strain for a live, oral typhoid vaccine. J Infect Dis 131:553–558

    Article  PubMed  CAS  Google Scholar 

  39. Wahdan MH, Serie C, Germanier R, Lackany A, Cerisier Y, Guerin N, Sallam S, Geoffroy P, el Tantawi AS, Guesry P (1980) A controlled field trial of liver oral typhoid vaccine Ty21a. Bull World Health Org 58:469–474

    PubMed  CAS  Google Scholar 

  40. Ivanoff B, Levine MM, Lambert PH (1994) Vaccination against typhoid fever: present status. Bull World Health Org 72:957–971

    PubMed  CAS  Google Scholar 

  41. Black RE, Levine MM, Ferreccio C, Clements ML, Lanata C, Rooney J, Germanier R (1990) Efficacy of one or two doses of Ty21a Salmonella typhi vaccine in enteric-coated capsules in a controlled field trial. Chilean Typhoid Committee. Vaccine 8:81–84

    Article  PubMed  CAS  Google Scholar 

  42. Ferreccio C, Levine MM, Rodriguez H, Contreras R (1989) Comparative efficacy of two, three, or four doses of TY21a live oral typhoid vaccine in enteric-coated capsules: a field trial in an endemic area. J Infect Dis 159:766–769

    Article  PubMed  CAS  Google Scholar 

  43. Simanjuntak CH, Paleologo FP, Punjabi NH, Darmowigoto R, Soeprawoto, Totosudirjo H, Haryanto P, Suprijanto E, Witham ND, Hoffman SL (1991) Oral immunisation against typhoid fever in Indonesia with Ty21a vaccine. Lancet 338:1055–1059

    Article  PubMed  CAS  Google Scholar 

  44. Levine MM, Ferreccio C, Cryz S, Ortiz E (1990) Comparison of enteric-coated capsules and liquid formulation of Ty21a typhoid vaccine in randomised controlled field trial. Lancet 336:891–894

    Article  PubMed  CAS  Google Scholar 

  45. Tucker SN, Tingley DW, Scallan CD (2008) Oral adenoviral-based vaccines: historical perspective and future opportunity. Expert Rev Vaccines 7:25–31

    Article  PubMed  CAS  Google Scholar 

  46. Lubeck MD, Davis AR, Chengalvala M, Natuk RJ, Morin JE, Molnar-Kimber K, Mason BB, Bhat BM, Mizutani S, Hung PP et al (1989) Immunogenicity and efficacy testing in chimpanzees of an oral hepatitis B vaccine based on live recombinant adenovirus. Proc Natl Acad Sci USA 86:6763–6767

    Article  PubMed  CAS  Google Scholar 

  47. Gomez-Roman VR, Grimes GJ Jr, Potti GK, Peng B, Demberg T, Gravlin L, Treece J, Pal R, Lee EM, Alvord WG, Markham PD, Robert-Guroff M (2006) Oral delivery of replication-competent adenovirus vectors is well tolerated by SIV- and SHIV-infected rhesus macaques. Vaccine 24:5064–5072

    Article  PubMed  CAS  Google Scholar 

  48. Xiang ZQ, Gao GP, Reyes-Sandoval A, Li Y, Wilson JM, Ertl HC (2003) Oral vaccination of mice with adenoviral vectors is not impaired by preexisting immunity to the vaccine carrier. J Virol 77:10780–10789

    Article  PubMed  CAS  Google Scholar 

  49. Sharpe S, Fooks A, Lee J, Hayes K, Clegg C, Cranage M (2002) Single oral immunization with replication deficient recombinant adenovirus elicits long-lived transgene-specific cellular and humoral immune responses. Virology 293:210–216

    Article  PubMed  CAS  Google Scholar 

  50. Appledorn DM, Aldhamen YA, Depas W, Seregin SS, Liu CJ, Schuldt N, Quach D, Quiroga D, Godbehere S, Zlatkin I, Kim S, McCormick JJ, Amalfitano A (2010) A new adenovirus based vaccine vector expressing an Eimeria tenella derived TLR agonist improves cellular immune responses to an antigenic target. PLoS One 5:e9579

    Article  PubMed  CAS  Google Scholar 

  51. Yarovinsky F, Zhang D, Andersen JF, Bannenberg GL, Serhan CN, Hayden MS, Hieny S, Sutterwala FS, Flavell RA, Ghosh S, Sher A (2005) TLR11 activation of dendritic cells by a protozoan profilin-like protein. Science 308:1626–1629

    Article  PubMed  CAS  Google Scholar 

  52. Ko SY, Cheng C, Kong WP, Wang L, Kanekiyo M, Einfeld D, King CR, Gall JG, Nabel GJ (2009) Enhanced induction of intestinal cellular immunity by oral priming with enteric adenovirus 41 vectors. J Virol 83:748–756

    Article  PubMed  CAS  Google Scholar 

  53. Belyakov IM, Moss B, Strober W, Berzofsky JA (1999) Mucosal vaccination overcomes the barrier to recombinant vaccinia immunization caused by preexisting poxvirus immunity. Proc Natl Acad Sci USA 96:4512–4517

    Article  PubMed  CAS  Google Scholar 

  54. Naito T, Kaneko Y, Kozbor D (2007) Oral vaccination with modified vaccinia virus Ankara attached covalently to TMPEG-modified cationic liposomes overcomes pre-existing poxvirus immunity from recombinant vaccinia immunization. J Gen Virol 88:61–70

    Article  PubMed  CAS  Google Scholar 

  55. Weyer J, Rupprecht CE, Mans J, Viljoen GJ, Nel LH (2007) Generation and evaluation of a recombinant modified vaccinia virus Ankara vaccine for rabies. Vaccine 25:4213–4222

    Article  PubMed  CAS  Google Scholar 

  56. Van Rompay KK, Abel K, Earl P, Kozlowski PA, Easlick J, Moore J, Buonocore-Buzzelli L, Schmidt KA, Wilson RL, Simon I, Moss B, Rose N, Rose J, Marthas ML (2010) Immunogenicity of viral vector, prime-boost SIV vaccine regimens in infant rhesus macaques: attenuated ­vesicular stomatitis virus (VSV) and modified vaccinia Ankara (MVA) recombinant SIV ­vaccines compared to live-attenuated SIV. Vaccine 28:1481–1492

    Article  PubMed  CAS  Google Scholar 

  57. Zhang J, Wu X, Qin C, Qi J, Ma S, Zhang H, Kong Q, Chen D, Ba D, He W (2003) A novel recombinant adeno-associated virus vaccine reduces behavioral impairment and ­beta-amyloid plaques in a mouse model of Alzheimer’s disease. Neurobiol Dis 14:365–379

    Article  PubMed  CAS  Google Scholar 

  58. Hara H, Monsonego A, Yuasa K, Adachi K, Xiao X, Takeda S, Takahashi K, Weiner HL, Tabira T (2004) Development of a safe oral Abeta vaccine using recombinant adeno-associated virus vector for Alzheimer’s disease. J Alzheimers Dis 6:483–488

    PubMed  CAS  Google Scholar 

  59. Eldridge JH, Meulbroek JA, Staas JK, Tice TR, Gilley RM (1989) Vaccine-containing biodegradable microspheres specifically enter the gut-associated lymphoid tissue following oral administration and induce a disseminated mucosal immune response. Adv Exp Med Biol 251:191–202

    PubMed  CAS  Google Scholar 

  60. Jones DH, Clegg JC, Farrar GH (1998) Oral delivery of micro-encapsulated DNA vaccines. Dev Biol Stand 92:149–155

    PubMed  CAS  Google Scholar 

  61. Kaneko H, Bednarek I, Wierzbicki A, Kiszka I, Dmochowski M, Wasik TJ, Kaneko Y, Kozbor D (2000) Oral DNA vaccination promotes mucosal and systemic immune responses to HIV envelope glycoprotein. Virology 267:8–16

    Article  PubMed  CAS  Google Scholar 

  62. Hedley ML, Curley J, Urban R (1998) Microspheres containing plasmid-encoded antigens elicit cytotoxic T-cell responses. Nat Med 4:365–368

    Article  PubMed  CAS  Google Scholar 

  63. O’ Hara AM, Shanahan F (2006) The gut flora as a forgotten organ. EMBO Rep 7:688–693

    Article  CAS  Google Scholar 

  64. McKee AS, MacLeod MK, Kappler JW, Marrack P (2010) Immune mechanisms of protection: can adjuvants rise to the challenge? BMC Biol 8:37

    Article  PubMed  CAS  Google Scholar 

  65. Miller SI, Kukral AM, Mekalanos JJ (1989) A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence. Proc Natl Acad Sci USA 86:5054–5058

    Article  PubMed  CAS  Google Scholar 

  66. Branger CG, Torres-Escobar A, Sun W, Perry R, Fetherston J, Roland KL, Curtiss R 3rd (2009) Oral vaccination with LcrV from Yersinia pestis KIM delivered by live attenuated Salmonella enterica serovar Typhimurium elicits a protective immune response against challenge with Yersinia pseudotuberculosis and Yersinia enterocolitica. Vaccine 27:5363–5370

    Article  PubMed  CAS  Google Scholar 

  67. Gomez-Duarte OG, Lucas B, Yan ZX, Panthel K, Haas R, Meyer TF (1998) Protection of mice against gastric colonization by Helicobacter pylori by single oral dose immunization with attenuated Salmonella typhimurium producing urease subunits A and B. Vaccine 16:460–471

    Article  PubMed  CAS  Google Scholar 

  68. Darji A, Guzman CA, Gerstel B, Wachholz P, Timmis KN, Wehland J, Chakraborty T, Weiss S (1997) Oral somatic transgene vaccination using attenuated S. typhimurium. Cell 91:765–775

    Article  PubMed  CAS  Google Scholar 

  69. Paglia P, Medina E, Arioli I, Guzman CA, Colombo MP (1998) Gene transfer in dendritic cells, induced by oral DNA vaccination with Salmonella typhimurium, results in protective immunity against a murine fibrosarcoma. Blood 92:3172–3176

    PubMed  CAS  Google Scholar 

  70. Kotton CN, Hohmann EL (2004) Enteric pathogens as vaccine vectors for foreign antigen delivery. Infect Immun 72:5535–5547

    Article  PubMed  CAS  Google Scholar 

  71. Kong W, Wanda SY, Zhang X, Bollen W, Tinge SA, Roland KL, Curtiss R 3rd (2008) Regulated programmed lysis of recombinant Salmonella in host tissues to release protective antigens and confer biological containment. Proc Natl Acad Sci USA 105:9361–9366

    Article  PubMed  CAS  Google Scholar 

  72. Liljebjelke KA, Petkov DI, Kapczynski DR (2010) Mucosal vaccination with a codon-optimized hemagglutinin gene expressed by attenuated Salmonella elicits a protective immune response in chickens against highly pathogenic avian influenza. Vaccine 28:4430–4437

    Article  PubMed  CAS  Google Scholar 

  73. Sadoff JC, Ballou WR, Baron LS, Majarian WR, Brey RN, Hockmeyer WT, Young JF, Cryz SJ, Ou J, Lowell GH et al (1988) Oral Salmonella typhimurium vaccine expressing circumsporozoite protein protects against malaria. Science 240:336–338

    Article  PubMed  CAS  Google Scholar 

  74. Tacket CO, Kelly SM, Schodel F, Losonsky G, Nataro JP, Edelman R, Levine MM, Curtiss R 3rd (1997) Safety and immunogenicity in humans of an attenuated Salmonella typhi vaccine vector strain expressing plasmid-encoded hepatitis B antigens stabilized by the Asd-balanced lethal vector system. Infect Immun 65:3381–3385

    PubMed  CAS  Google Scholar 

  75. Matsui H, Suzuki M, Isshiki Y, Kodama C, Eguchi M, Kikuchi Y, Motokawa K, Takaya A, Tomoyasu T, Yamamoto T (2003) Oral immunization with ATP-dependent protease-deficient mutants protects mice against subsequent oral challenge with virulent Salmonella enterica serovar typhimurium. Infect Immun 71:30–39

    Article  PubMed  CAS  Google Scholar 

  76. Silva AJ, Eko FO, Benitez JA (2008) Exploiting cholera vaccines as a versatile antigen delivery platform. Biotechnol Lett 30:571–579

    Article  PubMed  CAS  Google Scholar 

  77. Nakayama K, Kelly SM, Curtis III R (1988) Construction of ASD+ expression-cloning ­vector: stable maintenance and high level expression of cloned genes in a Salmonella vaccine strain. Nat Biotechnol 6:693–697

    Google Scholar 

  78. Ashraf S, Kong W, Wang S, Yang J, Curtiss R 3rd (2011) Protective cellular responses ­elicited by vaccination with influenza nucleoprotein delivered by a live recombinant attenuated Salmonella vaccine. Vaccine 29:3990–4002

    Article  PubMed  CAS  Google Scholar 

  79. Young Kang H, Curtiss R (2003) Immune responses dependent on antigen location in ­recombinant attenuated Salmonella typhimurium vaccines following oral immunization. FEMS Immunol Med Microbiol 37:99–104

    Article  CAS  Google Scholar 

  80. Lee P (2010) Biocontainment strategies for live lactic acid bacteria vaccine vectors. Bioeng Bugs 1:75–77

    Article  PubMed  Google Scholar 

  81. Steidler L, Neirynck S, Huyghebaert N, Snoeck V, Vermeire A, Goddeeris B, Cox E, Remon JP, Remaut E (2003) Biological containment of genetically modified Lactococcus lactis for intestinal delivery of human interleukin 10. Nat Biotechnol 21:785–789

    Article  PubMed  CAS  Google Scholar 

  82. Tangney M, van Pijkeren JP, Gahan CG (2010) The use of Listeria monocytogenes as a DNA delivery vector for cancer gene therapy. Bioeng Bugs 1:284–287

    Article  PubMed  Google Scholar 

  83. Galan JE, Nakayama K, Curtiss R 3rd (1990) Cloning and characterization of the asd gene of Salmonella typhimurium: use in stable maintenance of recombinant plasmids in Salmonella vaccine strains. Gene 94:29–35

    Article  PubMed  CAS  Google Scholar 

  84. Dietrich G, Bubert A, Gentschev I, Sokolovic Z, Simm A, Catic A, Kaufmann SH, Hess J, Szalay AA, Goebel W (1998) Delivery of antigen-encoding plasmid DNA into the cytosol of macrophages by attenuated suicide Listeria monocytogenes. Nat Biotechnol 16:181–185

    Article  PubMed  CAS  Google Scholar 

  85. Witte A, Wanner G, Blasi U, Halfmann G, Szostak M, Lubitz W (1990) Endogenous ­transmembrane tunnel formation mediated by phi X174 lysis protein E. J Bacteriol 172:4109–4114

    PubMed  CAS  Google Scholar 

  86. Peng W, Si W, Yin L, Liu H, Yu S, Liu S, Wang C, Chang Y, Zhang Z, Hu S, Du Y (2011) Salmonella enteritidis ghost vaccine induces effective protection against lethal challenge in specific-pathogen-free chicks. Immunobiology 216:558–565

    Article  PubMed  CAS  Google Scholar 

  87. Eko FO, Schukovskaya T, Lotzmanova EY, Firstova VV, Emalyanova NV, Klueva SN, Kravtzov AL, Livanova LF, Kutyrev VV, Igietseme JU, Lubitz W (2003) Evaluation of the protective efficacy of Vibrio cholerae ghost (VCG) candidate vaccines in rabbits. Vaccine 21:3663–3674

    Article  PubMed  CAS  Google Scholar 

  88. Mayr UB, Haller C, Haidinger W, Atrasheuskaya A, Bukin E, Lubitz W, Ignatyev G (2005) Bacterial ghosts as an oral vaccine: a single dose of Escherichia coli O157:H7 bacterial ghosts protects mice against lethal challenge. Infect Immun 73:4810–4817

    Article  PubMed  CAS  Google Scholar 

  89. Kudela P, Koller VJ, Lubitz W (2010) Bacterial ghosts (BGs)—advanced antigen and drug delivery system. Vaccine 28:5760–5767

    Article  PubMed  CAS  Google Scholar 

  90. Mayrhofer P, Tabrizi CA, Walcher P, Haidinger W, Jechlinger W, Lubitz W (2005) Immobilization of plasmid DNA in bacterial ghosts. J Control Release 102:725–735

    Article  PubMed  CAS  Google Scholar 

  91. Eko FO, He Q, Brown T, McMillan L, Ifere GO, Ananaba GA, Lyn D, Lubitz W, Kellar KL, Black CM, Igietseme JU (2004) A novel recombinant multisubunit vaccine against Chlamydia. J Immunol 173:3375–3382

    PubMed  CAS  Google Scholar 

  92. Macmillan L, Ifere GO, He Q, Igietseme JU, Kellar KL, Okenu DM, Eko FO (2007) A recombinant multivalent combination vaccine protects against Chlamydia and genital herpes. FEMS Immunol Med Microbiol 49:46–55

    Article  PubMed  CAS  Google Scholar 

  93. Bollen WS, Gunn BM, Mo H, Lay MK, Curtiss R 3rd (2008) Presence of wild-type and attenuated Salmonella enterica strains in brain tissues following inoculation of mice by ­different routes. Infect Immun 76:3268–3272

    Article  PubMed  CAS  Google Scholar 

  94. Halle S, Bumann D, Herbrand H, Willer Y, Dahne S, Forster R, Pabst O (2007) Solitary intestinal lymphoid tissue provides a productive port of entry for Salmonella enterica serovar Typhimurium. Infect Immun 75:1577–1585

    Article  PubMed  CAS  Google Scholar 

  95. Russmann H, Shams H, Poblete F, Fu Y, Galan JE, Donis RO (1998) Delivery of epitopes by the Salmonella type III secretion system for vaccine development. Science 281:565–568

    Article  PubMed  CAS  Google Scholar 

  96. Chen LM, Briones G, Donis RO, Galan JE (2006) Optimization of the delivery of heterologous proteins by the Salmonella enterica serovar Typhimurium type III secretion system for vaccine development. Infect Immun 74:5826–5833

    Article  PubMed  CAS  Google Scholar 

  97. Brumell JH, Tang P, Zaharik ML, Finlay BB (2002) Disruption of the Salmonella-containing vacuole leads to increased replication of Salmonella enterica serovar typhimurium in the cytosol of epithelial cells. Infect Immun 70:3264–3270

    Article  PubMed  CAS  Google Scholar 

  98. Hess J, Gentschev I, Miko D, Welzel M, Ladel C, Goebel W, Kaufmann SH (1996) Superior efficacy of secreted over somatic antigen display in recombinant Salmonella vaccine induced protection against listeriosis. Proc Natl Acad Sci USA 93:1458–1463

    Article  PubMed  CAS  Google Scholar 

  99. Gentschev I, Dietrich G, Spreng S, Kolb-Maurer A, Brinkmann V, Grode L, Hess J, Kaufmann SH, Goebel W (2001) Recombinant attenuated bacteria for the delivery of subunit vaccines. Vaccine 19:2621–2628

    Article  PubMed  CAS  Google Scholar 

  100. Shata MT, Hone DM (2001) Vaccination with a Shigella DNA vaccine vector induces antigen-specific CD8(+) T cells and antiviral protective immunity. J Virol 75:9665–9670

    Article  PubMed  CAS  Google Scholar 

  101. Peters C, Peng X, Douven D, Pan ZK, Paterson Y (2003) The induction of HIV Gag-specific CD8+ T cells in the spleen and gut-associated lymphoid tissue by parenteral or mucosal immunization with recombinant Listeria monocytogenes HIV Gag. J Immunol 170:5176–5187

    PubMed  CAS  Google Scholar 

  102. Mustafa W, Maciag PC, Pan ZK, Weaver JR, Xiao Y, Isaacs SN, Paterson Y (2009) Listeria monocytogenes delivery of HPV-16 major capsid protein L1 induces systemic and mucosal cell-mediated CD4+ and CD8+ T-cell responses after oral immunization. Viral Immunol 22:195–204

    Article  PubMed  CAS  Google Scholar 

  103. Butterton JR, Beattie DT, Gardel CL, Carroll PA, Hyman T, Killeen KP, Mekalanos JJ, Calderwood SB (1995) Heterologous antigen expression in Vibrio cholerae vector strains. Infect Immun 63:2689–2696

    PubMed  CAS  Google Scholar 

  104. Owen RL, Pierce NF, Apple RT, Cray WC Jr (1986) M cell transport of Vibrio cholerae from the intestinal lumen into Peyer’s patches: a mechanism for antigen sampling and for microbial transepithelial migration. J Infect Dis 153:1108–1118

    Article  PubMed  CAS  Google Scholar 

  105. del Rio B, Dattwyler RJ, Aroso M, Neves V, Meirelles L, Seegers JF, Gomes-Solecki M (2008) Oral immunization with recombinant lactobacillus plantarum induces a protective immune response in mice with Lyme disease. Clin Vaccine Immunol 15:1429–1435

    Article  PubMed  CAS  Google Scholar 

  106. Liu JK, Hou XL, Wei CH, Yu LY, He XJ, Wang GH, Lee JS, Kim CJ (2009) Induction of immune responses in mice after oral immunization with recombinant Lactobacillus casei strains expressing enterotoxigenic Escherichia coli F41 fimbrial protein. Appl Environ Microbiol 75:4491–4497

    Article  PubMed  CAS  Google Scholar 

  107. Mohamadzadeh M, Duong T, Sandwick SJ, Hoover T, Klaenhammer TR (2009) Dendritic cell targeting of Bacillus anthracis protective antigen expressed by Lactobacillus acidophilus protects mice from lethal challenge. Proc Natl Acad Sci USA 106:4331–4336

    Article  PubMed  CAS  Google Scholar 

  108. Bumann D, Metzger WG, Mansouri E, Palme O, Wendland M, Hurwitz R, Haas G, Aebischer T, von Specht BU, Meyer TF (2001) Safety and immunogenicity of live recombinant Salmonella enterica serovar Typhi Ty21a expressing urease A and B from Helicobacter pylori in human volunteers. Vaccine 20:845–852

    Article  PubMed  CAS  Google Scholar 

  109. Aebischer T, Bumann D, Epple HJ, Metzger W, Schneider T, Cherepnev G, Walduck AK, Kunkel D, Moos V, Loddenkemper C, Jiadze I, Panasyuk M, Stolte M, Graham DY, Zeitz M, Meyer TF (2008) Correlation of T cell response and bacterial clearance in human volunteers challenged with Helicobacter pylori revealed by randomised controlled vaccination with Ty21a-based Salmonella vaccines. Gut 57:1065–1072

    Article  PubMed  CAS  Google Scholar 

  110. Angelakopoulos H, Loock K, Sisul DM, Jensen ER, Miller JF, Hohmann EL (2002) Safety and shedding of an attenuated strain of Listeria monocytogenes with a deletion of actA/plcB in adult volunteers: a dose escalation study of oral inoculation. Infect Immun 70:3592–3601

    Article  PubMed  CAS  Google Scholar 

  111. Johnson PV, Blair BM, Zeller S, Kotton CN, Hohmann EL (2011) Attenuated Listeria monocytogenes vaccine vectors expressing influenza A nucleoprotein: preclinical evaluation and oral inoculation of volunteers. Microbiol Immunol 55:304–317

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Vaxart, Inc., San Francisco, CA, USA

    Wendy Peters, Ciaran D. Scallan & Sean N. Tucker

Authors
  1. Wendy Peters
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ciaran D. Scallan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sean N. Tucker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sean N. Tucker .

Editor information

Editors and Affiliations

  1. Novartis Vaccines Research, Cambridge, 02139, Massachusetts, USA

    Manmohan Singh

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Peters, W., Scallan, C.D., Tucker, S.N. (2013). Oral Vaccination: Attenuated and Gene-Based. In: Singh, M. (eds) Novel Immune Potentiators and Delivery Technologies for Next Generation Vaccines. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-5380-2_4

Download citation

Publish with us

Policies and ethics

Search

Navigation