15-病毒学virus巴斯德研究所.pptVIP

* Vaccines against viral diseases Vincent DEUBEL Course on Basic Virology and Immunology, 2006 Virus infection Type of virus Nature of virus Dose of virus Routes of infection Oral Nasal Cutaneous Intradermal Parenteral Sexual Host Age Race Genetic predispos. Immune status Health condition Nutritional cond. Immune mechanisms against viral infection Nature of responses Type of responses Level of responses Nature of adaptive immunity: concern for vaccines Humoral Protective Surface antigen (Nt, ADC’L, ADCC) (Receptor-Fusion) Major contribution to (re)infection Long-lasting memory Evasion to Nt: carbohydrates (E protein vaccine without carbohydrates?) mutations Reassortment Nature of adaptive immunity: concern for vaccines Cellular CD4 helper Barely protective (m) Major viral antigens (MHC II) CD8 CTL Barely protective (M) All viral antigens (MHC I)-b2M) Contribution to infected cell elimination Contribution to restrict virus replication (CD8-cytokines) Cooperation in B-cell response (CD4H) But epitope and MHC dependent Nature of adaptive immunity: concern for vaccines Neutralizing antibodies against envelope protein Non neutralizing antibodies may have anti-viral activity IgG vs IgA anti-viral activity. Way of vaccination? ADE phenomenon Role of ADCC and ADC’L T-cell immunity less efficient and HCM dependent CTL may be deleterious (balance) Conclusions: Nature of adaptive immunity: concern for vaccines (cont.) Real advantage of incorporation of CTL epitopes in a vaccine preparation? MHC-dependent Short duration of immunity Small number of epitopes in a virus Escape mutants by mutation inside the epitope Varaibility of the strength of immunity among epitopes Possible CTL-driven immunopathogenesis Peptide vaccine not good CTL inducer Active only on infected cells Role of Non Nt Ab in protection against virus infection Immune complex with virus induces clearance Abs directed against envelope protein prevent virus re