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Immune Relevancy (So What?) As related to Pathogenesis, Diagnosis and Vaccine Efficacy

Immune Relevancy (So What?) As related to Pathogenesis, Diagnosis and Vaccine Efficacy. Response correlates to disease or protection? Ag-dependent. Response correlates to disease or protection? Ag-dependent. Environmental mycobacteria, helminths, genetics, age, …. Vaccination.

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Immune Relevancy (So What?) As related to Pathogenesis, Diagnosis and Vaccine Efficacy

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  1. Immune Relevancy (So What?) As related to Pathogenesis, Diagnosis and Vaccine Efficacy Response correlates to disease or protection? Ag-dependent Response correlates to disease or protection? Ag-dependent Environmental mycobacteria, helminths, genetics, age, … Vaccination M. bovis challenge Necropsy Environmental mycobacteria, helminths, genetics, age, … Response correlates to disease or protection? Ag-dependent M. bovis challenge Necropsy

  2. Effector Responses - Positive Correlation to Infection  IFN-, ng/ml M. bovis PPD rESAT-6:CFP10 Central Memory Responses Prior to Challenge IFN- BCG RD1 Non-vaccinated Central Memory Responses - Positive Correlation to Protection Spearman r = -0.8195 (p <0.0001) IFN- IFN- > 7 < 7 Cumulative Pathology Score

  3. Activation Associated Events • Recall Responses to PPD or RD1 antigens, • After Challenge • Protected versus Non-protected • (BCG- or RD1-vaccinates) versus (non- and/or mc26030-vaccinates): • Decreased Antigen-Specific Response (mRNA) • (IFN-, iNOS, IL-4, IL-5, MIP1-)  • Diminished Activation Phenotype, mfi or % • (CD25, CD44, MHCII, CD80/86 and CD62L) • Decreased Antigen Specific Proliferation • primarily w/ CD4 subset • No effect on skin test - vaccines elicit a response to PPD’s

  4. +Ag, +IL-2, 12-14 days Cultured: Central memory ‘CM’: +Ag, +APC, 24 h Cultured ELISPOTs: a method to assess memory T cells PBMC: EM CM ‘ex vivo’: effector and effector memory T cells

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