1 / 17

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

inez
Download Presentation

Mucosal Vaccines: Prevention of Caries and Periodontal Diseases

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  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

More Related