1. 1 Workshop on the immunological basis of vaccine efficacy Vaccine and Infectious Disease Institute December 14, 2009 Ira M. Longini, Jr. Center for Statistical and Quantitative Infectious Diseases (CSQUID) Vaccine and Infectious Disease Institute Fred Hutchinson Cancer Research Center and The University of Washington Seattle Washington

2. 2 The State of Vaccinology We need immune markers for vaccine protect against infection, disease and transmission. We need to predict vaccine efficacy and effectiveness as well as indirect effectiveness from immunogenicity data. Up until now, estimation of VE has been an empirical science based on phase III vaccine trials

3. 3 Guiding Principles Up Until Now We only care if vaccines work We don’t care how they work Problems with this – Need phase III trials for licensure Sometimes immunological bridging works – So far, we have failed to develop truly effective vaccines for complex infections and mutagenic agents, e.g., Malaria TB HIV Flu

4. 4 Solution Identify and quantify correlates of protection and surrogates of efficacy – Humoral (antibody) level – Cell mediated immunity Need within host models of the immune response coupled with transmission models Need phase III human trials where both immunological and clinical data available on same subjects Animal models

5. 5 Today’s Workshop Session I – Statistical Basics Session II - III – Immune memory and dynamics of the immune response Session IV – T – cell based vaccines

6. 6 Tuesday Morning Informal discussion of workshop concepts 10 am - noon M5-C815 Arnold Building

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9. 9 The End