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Vaccines for Gonorrhea: Can We Rise to the Challenge?

By Weiyan Zhu, Ching-Ju Chen, Christopher E. Thomas, James E. Anderson, Ann E. Jerse and P. Frederick Sparling

Abstract

Immune responses to the gonococcus after natural infection ordinarily result in little immunity to reinfection, due to antigenic variation of the gonococcus, and redirection or suppression of immune responses. Brinton and colleagues demonstrated that parenteral immunization of male human volunteers with a purified pilus vaccine gave partial protection against infection by the homologous strain. However, the vaccine failed in a clinical trial. Recent vaccine development efforts have focused on the female mouse model of genital gonococcal infection. Here we discuss the state of the field, including our unpublished data regarding efficacy in the mouse model of either viral replicon particle (VRP) vaccines, or outer membrane vesicle (OMV) vaccines. The OMV vaccines failed, despite excellent serum and mucosal antibody responses. Protection after a regimen consisting of a PorB-VRP prime plus recombinant PorB boost was correlated with apparent Th1, but not with antibody, responses. Protection probably was due to powerful adjuvant effects of the VRP vector. New tools including novel transgenic mice expressing human genes required for gonococcal infection should enable future research. Surrogates for immunity are needed. Increasing antimicrobial resistance trends among gonococci makes development of a vaccine more urgent

Topics: Microbiology
Publisher: Frontiers Research Foundation
OAI identifier: oai:pubmedcentral.nih.gov:3109613
Provided by: PubMed Central

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Citations

  1. (1985). A community-based outbreakofapenicillin-resistantNeisseriagonorrhoeae not producing penicillinase (chromosomally mediated resistance).
  2. (2002). A cooperative interaction between Neisseria gonorrhoeae and complement receptor 3 mediates infection of primary cervical epithelial cells.
  3. (2010). A phase 1 study of a group B meningococcal native outer membrane vesicle vaccine made from a strain with deleted lpxL2 and synX and stable expression of opcA.
  4. (1996). A viral vaccine vector that expresses foreign genes in lymph nodes and protects against mucosalchallenge.J.Virol.70,3781–
  5. A.(2005).HumanC4b-bindingprotein selectively interacts with Neisseria gonorrhoeae and results in species-specificinfection.Proc.Natl.
  6. (2008). Alpha virus replicon particles acting as adjuvants promote CD8+ T cell responses to codelivered antigen.
  7. (2011). Alphavirus replicon-based adjuvants enhance the immunogenicity and effectiveness of FluzoneR in rhesus macaques. Vaccine 931–940.
  8. (2010). Alphavirus replicon-based enhancement of mucosal and systemic immunity is linked to the innate immune response generated by primary immunization.
  9. and Atkinson,J.(1974).Gonococcalvaccine studies in Inuvik.
  10. article was submitted to Frontiers in Cellular and Infection Microbiology, a specialty of Frontiers
  11. (2009). Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis.
  12. (1977). Bactericidal antibody in genital infection due to Neisseria gonorrhoeae.
  13. (2008). Bactericidal antibody responses induced by meningococcal recombinant chimeric factor H-binding protein vaccines.
  14. (1998). Binding of complement factor H to loop 5 of porin protein 1A: a molecular mechanism of serum resistance of nonsialylated Neisseria gonorrhoeae.
  15. (2010). Bovine prolactin promotes the expression of human transferrin in the milk of transgenic mice.
  16. (2008). CEACAM1 and the regulation of mucosal inflammation.
  17. (2008). CEACAM1 dynamics during Neisseria gonorrhoeae suppression of CD4+ T lymphocyte activation.
  18. (2008). Cefibuten resistance and treatment failure of Neisseria gonorrhoeae infection.
  19. (2010). Cephalosporin creep among gonococci: time for a pharmacodynamic rethink?
  20. (2006). Characterization of a peptide vaccine candidate mimicking an oligosaccharide epitope of Neisseria gonorrhoeae and resultant immune responses and function.
  21. (1998). Characterization of a subunit structure and stability of the recombinant porin from Neisseria gonorrhoeae.
  22. (1989). Class specific antibody response to gonococcal infection.
  23. (2008). Clinically relevant mutations that cause derepression of the Neisseria gonorhoeae MtrC-MtrD-MtrE efflux pump systemconferdifferentlevelsof antimicrobialresistanceandinvivofitness.
  24. (2005). Comparison of immune responses to gonococcal PorB delivered as outer membrane vesicles, recombinant protein, or Venezuelan equine encephalitis viral replicon particles.
  25. (2001). Correlation of in vitro susceptibilities to newer quinolones of naturally occurring quinolone-resistant Neisseria gonorrhoeae strains with changes in GyrA and ParC.
  26. (2010). Critical role of Th17 responses in a murine model of Neisseria gonorrhoeae genital infection.
  27. (1998). Cytokine and antibody responses in women infected with Neisseria gonorhoeae: effects of concomitant infections.
  28. (2008). Defining targets for complement components C4b and C3b on the pathogenic neisseriae.
  29. (2007). Development and preclinicalevaluationof analphavirusrepliconvaccineforinfluenza.Vaccine 25,
  30. (1991). Efficacy trial of a parenteral gonococcal pilus vaccine in men.
  31. (2010). Emergence, spread, and characteristics of Neisseria gonorrhoeae isolates with in vitro decreased susceptibility and resistance to extended-spectrum cephalosporins in Sweden.
  32. (1989). Epidemiologic evidence for the development of serovarspecific immunity after gonococcal infection.
  33. (1999). Experimental gonococcal genital tract infection and opacity protein expression in estradiol-treated mice.
  34. (2001). Experimental gonococcal urethritis and reinfection withhomologousgonococciinmale volunteers.
  35. (1942). Experimental infection with Neisseria gonorrhoeae.Am.
  36. (2007). Factor H binding and function in sialylated pathogenic neisseriae is influenced by gonococcal, but not meningococcal,
  37. (1991). Fate of the major outer membrane protein P.1A in early and late events of gonococcal infection of epithelial cells.
  38. (1975). Field trials of a gonococcal vaccine.
  39. (1999). From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection.
  40. (2009). Functional characterization of antibodies against Neisseria gonorrhoeae opacity protein loops.
  41. (2010). Generation of human CEACAM1 transgenic mice and binding of Opa protein to their neutrophils.
  42. (1982). Genital antibody response to a parenteral gonococcal pilus vaccine.
  43. (1990). Gonococcal outer membrane-protein P1B: comparative sequence analysis and localization of epitopes which are recognized by type-specific and crossreacting monoclonal antibodies.
  44. (1980). Gonococcal salpingitis is less likely to recur with Neisseria gonorrhoeae of the same principal outer membrane protein antigenic type.
  45. (2007). Gonococcal transferrin binding protein chimeras induce bactericidal and growth inhibitory antibodies in mice.
  46. (2007). HIV-1 infection and pathogenesis in a novel humanized mouse model.
  47. (2007). Host glycoprotein Gp96 and scavenger receptor SREC interact with PorB of disseminating Neisseria gonorrhoeae in an epithelial invasion pathway.
  48. (2008). Human factor H interacts selectively with Neisseria gonorrhoeae andresultsinspecies-specific complement evasion.
  49. (1969). Human immunity to the meningococcus. I. The role of humoral antibodies.
  50. (1969). Human immunity to the meningococcus. II. Development of natural immunity.
  51. Identification of a new OmpAlike protein in Neisseria gonorrhoeae involved in the binding to human epithelial cells and in vivo colonization.
  52. (1976). Immunity in infection with Neisseria gonorrhoeae: duration and serological response in the chimpanzee.
  53. Immunogenicity of Neisseria gonorrhoeae lipooligosaccharide epitope, 2C7, widely expressed in vivo with no immunochemical similarity human glycosphingolipids.
  54. (2010). Immunogenicity of two investigational serogroup B meningococcal vaccines in the first year of life: a randomized comparative trial.
  55. (1995). Inflammatory cytokines produced in response to experimental human gonorrhea.
  56. (2010). Innate immune functions of the neisserial porins andtherelationshiptovaccineadjuvant activity.
  57. (2010). Interactions betweenbacterialpathogensandthe mitochondrial cell death pathways.
  58. (2005). Intranasal administration of recombinant Neisseria gonorrhoeae transferrin binding proteins A and B conjugated to the cholera toxin B subunit induces systemic and vaginal antibodies in mice.
  59. (2000). Intranasalimmunizationwithgonococcal outer membrane preparations reduces the duration of vaginal colonization of mice by Neisseria gonorrhoae.
  60. J.(2009).Bactericidalantibodyisthe immunological surrogate of protection against meningococcal disease.
  61. K.(1974).Asymptomaticgonorrhea in men. Diagnosis natural course, prevalence and significance.
  62. (2011). K.R.,Ala’aldeen,D.A.,Crook,D.W., www.frontiersin.org
  63. (1999). Limited local and systemic antibody responses to Neisseria gonorrhoeae duringuncomplicatedgenital infections.
  64. (2008). Local and humoral immune responses against primary and repeat Neisseria gonorrhoeae genital tract infections of 17 betaestradiol-treated mice.
  65. (1999). Longitudinal evaluation of serovarspecific immunity to Neisseria gonorrhoeae.
  66. (2009). Meningococcal outer membrane vesicle vaccines derived from mutant strains engineered to express factor H binding proteins from antigenic variant groups 1 and 2.
  67. (2007). Molecular characterization of the interaction between porins of Neisseria gonorrhoeae and C4b-binding protein.
  68. (1999). Molecular typing of Neisseria gonorrhoeae causing repeated infections: evolution of porin during passage within a community.
  69. (1986). Monoclonal antibodies to gonococcal membrane protein 1B; use in investigation of the potential protective effect of antibodies directedagainstconservedandtypespecific epitopes.
  70. (2006). Mucosal and systemic adjuvant activity of alphavirus replicon particles.
  71. (2010). Multicenter, open-label, randomized phase II controlled trial of an investigational recombinant meningococcal serogroupB vaccine with and without outer membrane vesicles, administered in infancy.
  72. (1994). Multiple gonococcal opacity proteins are expressed during experimental urethral infection in the male.
  73. (2006). Neisseria gonorrhoeae delays the onset of apoptosis in polymorphonuclear leukocytes.
  74. (2005). Neisseria gonorrhoeae kills carcinoembryonic antigen-related cellular adhesion molecule 1 (CD66a)-expressing human B cells and inhibits antibody production.
  75. (2008). Neisseriagonorrhoeae suppressesthe oxidative burst of human polymorphonuclear leukocytes.
  76. (2002). Neisserial binding to CEACAM1 arrests the activation and proliferation of CD4+ T lymphocytes.
  77. (2009). Novel humanized murine models for HIV research.
  78. (2010). Opacity proteins increase fitnessinthefemalegenitaltractdue to a factor under ovarian control.
  79. (2011). paper pending published: 07
  80. (2009). Pathogenic neisseria: surface modulation, pathogenesis and infection control.
  81. (1985). Pilus vaccines.
  82. (1989). Protein III structure, function, and genetics.
  83. (2010). Qualitative and quantitativeassessmentofmeningococcal antigens to evaluate potential strain coverage of protein-based vaccines.
  84. (2009). Resistance of Neisseria gonorrhoeae to non-oxidative killing byadherenthumanpolymorphonuclear leukocytes.
  85. (1976). Serum and secretory antibody responses to Neisseria gonorrhoeae in patients with gonococcal infections.
  86. (1974). Serum resistance of Neisseria gonorhoeae.D o e si tt h w a r tt h e inflammatoryresponseandfacilitate the transmission of infection?
  87. (2010). Sexually transmitted diseases treatmentguidelines.MorbidityandMortality
  88. (2006). Sialyltransferase enhances Neisseria gonorrhoeae survivalduringexperimental murine genital tract infection.
  89. (1999). Structural and immunochemical characterization of a Neisseria gonorrhoeae epitope defined by a monoclonal antibody 2C7; the antibodyrecognizesaconservedepitopeonspecificlipooligosaccharides inspiteof presenceof humancarbohydrate epitopes.
  90. (1978). Studiesontherelationshipsbetween serum bactericidal activity and uncomplicated genital infections due to Neisseria gonorrhoeae.
  91. (2010). Systems vaccinology.
  92. (2008). T-cell quality in memory and protection: implications for vaccine design.
  93. (2008). The contribution of type I interferon signaling to immunity induced by alphavirus replion vaccines.
  94. (1982). The development of a Neisserial pilus vaccine for gonorrhea and meningococcal meningitis,”
  95. (2005). The frequency and rate of pilin antigenic variation in Neisseria gonorrhoeae.
  96. (1998). The gonococcal t r a n s f e r r i nr e c e p t o ri sr e q u i r e df o r humaninfection.Mol.Microbiol.27,
  97. (2010). The gonococcus fights back:is this time a knock-out?
  98. (2005). The interactions of Neisseriagonorrhoeae withadherent polymorphonuclear leukocytes.
  99. (2010). the meningococcal vaccine candidate neisserial surface proteinA (NspA). binds to factor H and enhances meningococcal resistance to complement.
  100. (2004). The molecular mechanisms usedbyNeisseriagonorrhoeae toinitiate infection differ between men andwomen.Clin.Microbiol.Rev.17,
  101. (1989). The potential protective effect of immunization with outer membrane protein 1 from Neisseria gonorrhoeae.
  102. (2003). The role of porins in neisserial pathogenesis and immunity.
  103. (2010). Transgenic mice expressing variants of complement factor H develop AMD-like retinal findngs.
  104. (2007). Update on the management of gonorrhea in adults in the United States.
  105. (2006). Vaccination of mice with gonococcal TbpB expressed in vivo from Venezuelan encephalitis viral replicon particles.
  106. (2011). Vaccine for gonorrhea?
  107. (1995). Vaccines for gonorrhea: where are we on the curve? Trends Microbiol.
  108. W.M.,andStaats,H.F.(2010).Effective induction of protective systemic immunitywithnasallyadministered vaccines adjuvanted with IL-1.