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CORRELATES OF IMMUNE PROTECTION Concluding remarks Why are Correlates of Immunity Important ? 1. 2. 3. 4. 5. 6. Basic immunology Enables correct choice of vaccine antigen To permit consistency of potency To determine susceptibility of an individual or a population If efficacy trial not feasible or ethical, immunological data enable licensure of vaccine Enables bridging from first-generation vaccine to second generation Plotkin Definitions • Correlate of Protection (CoP):An immune response that is statistically interrelated with protection • Absolute Correlate: A specific level of response highly correlated with protection: a threshold • Relative Correlate: Level of response variably correlated with protection • Co-Correlate:One of two or more factors that • correlate with protection in alternative, additive, or synergistic ways. Correlates of Protection • Confounded by • Inoculum size • Genetics of the host • Cholera • ETEC • Norovirus • Rotavirus? • Age group Correlates of Protection Good correlate Not bad Needs work Hepatitis A Rotavirus Everything else Vi typhoid Cholera Polio Norvirus Looking ahead • Holmgren: There is a strong need for methods to measure circulating memory cells after oral vaccination that could predict long term immune protection • How will vaccines administered to infants and children interact with natural exposure • Kotloff: Several MSD diarrhea pathogens are associated with linear growth faltering. • Kosek developed a scoring system for diarrhea episodes that are associated with nutritional outcomes. • Additional emphasis may be needed on this outcome for vaccine development. • How to increasingly use validated assays Building on success: understanding difficulties