Infectious Diseases in an Age of Change The Impact of Human Ecology and Behavior on Disease Transmission (1995) / Chapter Skim
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Vaccines for Bacterial Sexually Transmitted Infections: A Realistic Goal?
Vaccines for Bacterial Sexually Transmitted Infections: A Realistic Goal?
Pages 213-234
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From page 213... ...
have received relatively less research and clinical attention compared with HIV. Use of a combination of approaches, including public education and accessible treatment clinics, in many nations in the industrialized West has resulted in dramatic declines in incidence of most bacterial STDs in the last 1~14 years, particularly gonorrhea (1, 2~.
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Both gonorrhea and genital chlamydia are major causes of salpingitis, ectopic pregnancy, and infertility. A sense of urgency for the control of these diseases has emerged recently because of evidence that they significantly increase the rate of HIV transmission between sexual partners (~9~.
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Development of chancre immunity is correlated with a vigorous humoral and cellular immune response to multiple antigens (21~. After several weeks of untreated early syphilis, treponemes are cleared from the primary and secondary lesions.
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activities, either of which could contribute to immunity, develop during infection. Mechanisms by which treponemes persist in the presence of vigorous IgG, IgM, and cellular immune responses to multiple antigens (reviewed in ref.
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pallidum thus are termed TROMPs treponemal rare outer membrane proteins.
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In more recent times, a variety of crude or partially purified antigens were used to vaccinate experimental animals against gonorrhea, with modestly encouraging results. For instance, immunization of chimpanzees with a whole-cell killed vaccine made from a chimpanzee virulent isolate conferred partial resistance to urethral challenge (42~.
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By use of synthetic peptide technology, the common PorB epitope that reacts with the broadly protective PorB-specific mAb SM24 was defined as YSIP (55~. The common PorA epitope that reacts with the broadly protective PorA-specific mAb SM101 (51)
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Recently, it has been possible to construct recombinant Salmonella typhimurium strains that express gonococcal Por constitutively from the por promoter without evident toxicity to the host strain (63~. This should allow studies of the vaccine potential of Por delivered to the gut immune system and of the ability of Por to protect against homologous and h=~=rm]
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The rapidity and extent of Pil antigenic variation might help to explain how gonococci escape a vigorous immune response, and/or how gonococci rapidly adapt to adhere to quite different cells in diverse ecological niches (cervix, urethra)
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Over Possible Gonococcal Vaccines Opacity proteins (Opa) are a family of up to 11 or 12 related outer membrane proteins that, like pill, also serve as adherence ligands, undergo high-frequency phase and antigenic variations, and appear to be necessary to establish genital infection (81~.
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(ii) Phase and antigenic variations affect the length and composition of core sugars and loss of terminal epitopes helps to evade antibodies against the core, although gonococci with a truncated core are complement sensitive.
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~ nere na~ oeen re~arKao~e ~nere nas oeen remarkable progress in understanding the immunopathogenesis of chlamydia infections in the past decade, and a vaccine for genital chlamydia is now a realistic hope. Heat Shock Prote~ns and Hypersensi~civ~ty Important lessons were learned from attempts to develop a vaccine against trachoma (reviewed in ref.
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, and exciting recent evidence suggests that IFN-y may result in a persistent, quiescent infection in which chlamydia express normal amounts of 57-kDa GroEL homologue but markedly decreased amounts of MOMP and other outer membrane antigens (111~. If confirmed, this would help to explain how the immune response leads to chronic infection, and subsequently to a tissue-damaging hypersensitivity response to crossreacting host heat shock protein antigens.
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Murine immune responses to chlamydial heat shock proteins are H-2 linked (113) which could help to explain why only a proportion of persons develop immune-related complications, assuming similar genetic control of anti-chlamydia responses in humans.
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MOMP does not appear to be protected by blocking antibodies or by strategies analogous to sialylation of LOS, both of which at least partially protect Por in gonococci. This suggests that it may prove to be easier to develop chlamydial MOMP vaccines than gonococcal Por vaccines.
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Progress has been greatest for Neisseria gonorrhoeae and Chlamydia trachomatis. Present emphasis is on the major or principal outer membrane proteins of N
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The Global AIDS Strategy (WHO, Geneva) , WHO AIDS Series, 11.
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(1985) in Monoclonal Antibodies Against Bacteria, eds.
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Vaccines for Bacterial Sexually Transmitted Infections / 233 120. Zhang, Y.-X., Stewart, S
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