Medical Research

Center for Infectious Disease Research

Alexis Kaushansky, Noah Sather
Seattle, WA
$1,000,000
June 2018

Recently, several promising experimental vaccines have failed to achieve efficacy in the field after they demonstrated high levels of protection in human clinical trials involving pathogen naïve individuals.  Early clinical trials typically study the first exposure to infection while in the field, people are often infected with a pathogen multiple times before vaccination.  Investigators at the Center for Infectious Disease Research in Seattle, Washington, hypothesize that the resultant partial “immunity” alters the engagements between the pathogen and the host.  This impacts the development of potent immune effector cells and in turn reduces the efficacy of vaccine-induced protection.  Each of these processes is complicated by the reality that, while most studies evaluate bulk measurements, infection and immunity are both driven by a very small number of individual cells whose characteristics are likely lost in the context of bulk measurements.  The team proposes to evaluate changes that occur in host-parasite interactions as a result of pre-existing humoral immunity to malaria infection, as well as determine the impact of these changes on vaccine efficacy.  Importantly, assessments will occur at the single cell level, allowing evaluation of how parasites, host target cells and antibody responses interact to yield protection or susceptibility to infection.

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