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Mucosal Vaccines: Prevention of Caries and Periodontal Diseases

Mucosal Vaccines: Prevention of Caries and Periodontal Diseases. Most infections occur or emanate from mucosal surfaces. Gastrointestinal tract

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Mucosal Vaccines: Prevention of Caries and Periodontal Diseases

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  1. Mucosal Vaccines: Prevention of Caries and Periodontal Diseases

  2. Most infections occur or emanate from mucosal surfaces • Gastrointestinal tract • Helicobacter pylori, Vibrio cholerae, enterotoxigenic E. coli, Salmonella, Shigella spp., Campylobacter jejuni, Clostridium difficile, rotaviruses, and calici viruses • Respiratory tract • Mycoplasma pneumoniae, influenza virus, respiratory syncytial virus (RSV) • Urogenital tract • HIV, Chlamydia, Neisseria gonorrhoeae, herpes simplex virus (HSV) and E. coli (urinary tract infections) • Oral cavity • Streptococcus mutans, Porphyromonas gingivalis, Candida albicans

  3. Goals for the development of a vaccine • Prevent agent from attaching or colonizing the mucosal epithelium (non-invasive agents) • Prevent penetration and replication within the mucosal epithelium (invasive agents) • Block binding or action of toxin • Induce a protective sIgA response • Modulate systemic response?

  4. Requirements of Protective Vaccines • Block adherence of microorganism to host • Facilitate clearance from host • Neutralize toxin • Must induce recognition of “virulence” epitopes • Must be immunogenic • Must not induce autoimmune disease • Should induce long-lasting immunity • Must induce the type of response that is effective to eliminate pathogen (eg. TH1 or TH2)

  5. Strategies for Mucosal Immunization • Requirements • Safe taken orally • Long-term maintenance of memory • Survive in gastric and intestinal environments • Must escape normal clearance mechanisms • Must compete for inclusion within M-Cell transport • Must arrive intact to antigen-processing cells • Must induce dimeric sIgA reactive with cell surface

  6. Strategies for Immunization (cont’d) • Strategies for Delivery of Vaccine Into O-MALT • Inert particulate carriers • Biodegradable copolymers • Immune-stimulating complexes (ISCOMs) • Hydroxyapatite crystals • Live vaccine vectors (recombinant) • Vaccinia virus • Salmonella • Mycobacterium bovis

  7. Strategies for Immunization (cont’d) • Strategies for Enhancing Mucosal Immune Response • Co-delivery with cytokines • Co-immunogens (Cholera toxin) • Peptides presented with potent T-cell epitopes

  8. Time course of sIgA appearance Gestation Birth 8w 11w 19w 26w 2-4w 1m 3m 6m 2y ? SC Bronchial Epithel- ium SC Salivary Gland Saliva: Adult SC No IgA Salivary Antibody to Initial Oral and Gut Flora Tooth Eruption Adult Concen- trations Peyer’s Patches IgA Cells Saliva sIgA Early IgA Peak Many Salivary IgA Concentrations in Adult Range Adapted from Taubman & Smith, 1993

  9. Issues in Oral Health • Most oral infections are polymicrobial infections • Most are chronic infections • What is the etiologic agent? • Caries • Periodontal disease • What are the virulence factors? • What is the “at risk” population? • Are there easier alternatives? • Who do you immunize? • Most are not life-threatening

  10. What are the risks? • Cross-reaction with host antigens • Infection with live vaccines • Syndromes

  11. An example of a phase I anti-caries clinical trial • Goal of study • Induction of sIgA by mucosal immunization with S. mutans antigen in lipid monolayer • Comparison of nasal vs. tonsillar immunization (topical spray) • Safety • Antigen • E-GTF (enriched glucosyltransferase preparation) neet or in a liposomal vaccine preparation (lipid monolayer) • Subjects • Twenty-one adults (20-50 years of age)

  12. Goals (cont’d) • Examine sIgA response in: • Parotid saliva • Nasal washes • Serum (IgG and IgA)

  13. Protocol • Samples collected at various intervals following immunization (0, one to two week intervals for three months)

  14. Anti-GTF in Nasal washes • Panels • Upper (IN immunized) • No difference between soluble and liposomal • Lower (IT vs IN) • Nasal better than tonsil

  15. Anti-GTF in Parotid Saliva • Panels • Upper (IN immunized) • No difference between soluble and liposomal • Lower (IT vs IN) • Nasal better than tonsil on day 35

  16. Anti-GTF Serum Responses • Panels • Upper (IgG response) • Nasal better than tonsil • Not statistically-significant • Lower (IgA response) • Nasal better than tonsil • Not statistically-significant

  17. Conclusion • Soluble and liposomal GTF appear to be safe • Immunogenic when given in nasal route • In conflict with other studies • These were adults, may be different in children

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