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General classes of vaccines

General classes of vaccines. An induced mobilization of the immune response for the purpose of therapeutic benefit. Preventative: infectious agents Therapeutic: cancer. General classes of vaccines.

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General classes of vaccines

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  1. General classes of vaccines An induced mobilization of the immune response for the purpose of therapeutic benefit. Preventative: infectious agents Therapeutic: cancer

  2. General classes of vaccines Antibody response CD4+ T cells, B cells MHC class II-dependentCellular response cytotoxic CD8+ T cells, NK cells MHC class I-dependent

  3. Classical success: polio virus • oral route of infection • initial replication in GI tract • vaccine: killed/attenuated virus • injected (Salk) • oral (Sabin)

  4. Paroxysmal success: influenza • infects via airway • epithelial/systemic replication • killed/attenuated virus, protein • antibody to viral spike glycoprotein • (hemagglutinin, HA) confers protection HA genetic drift subverts antibody

  5. Unmitigated failure: HIV • infects via anal/vaginal epithelia • replication/residence in immune cells • killed/attenuated virus • recombinant envelope glycoprotein • poor protection, cumbersome trials >80 million infected individuals/victims 3.1 million new cases/year in Africa alone

  6. Why have HIV vaccines failed? • gp120 genetic drift subverts antibody • virus is rarely extracellular • wrong viral component, wrong delivery? • underdesigned? • or…overdesigned?

  7. Typical antigen formulations • peptides bound to carriers (adjuvants) • recombinant proteins • killed or attenuated virus/bacteria • DNA or mRNA encoding protein antigen

  8. Typical vaccine delivery vehicles • injection in adjuvant (skin, muscle) • oral, nasal • recombinant or synthetic viral vector • transformed microbial vector

  9. Engineering rational vaccines • understand biology of target • understand biology of response bioengineering

  10. Production of MHC class I & II-peptide complexes Virus-encoded proteins

  11. “Cross presentation” of exogenous antigens on MHC class I: CD8 responses to extracellular agents

  12. Dendritic cells initiate antigen-specific immune responses • most efficient of all APCs • high MHC class I, II & costimulators • efficient cross presentation • stimulate naïve T cells (CD4, CD8) • initiate Ag-specific immune responses All immunization strategies must target DCs

  13. Immature: antigen capture Mature: antigen presentation

  14. Multiple inducers of DC maturation immature DC mature DC Microbial products / TLR ligands Viral products Inflammatory cytokines Signaling receptors various T cell responses

  15. Targeting DCs to elicit immunity: engineering requirements • The optimal delivery device… • will be targetable to selected DC populations • can be coupled to DC maturation agents (microbial, inflammatory, other?) • can accomodate any type of antigen • permits intracellular targeting (cross-presentation from cytosol favors cytotoxic T cell responses) • traceable (does it reach DCs, nodes?) • modular (permits efficient, small-scale trials) • synthetic, stable, orally available for global use

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