| Antibodies are known to be a primary correlate of protection in almost all current vaccines, and thus evaluating the antibody response is of critical importance in attempting to predict the efficacy of novel vaccine candidates. Historically antibody responses have generally been detected by measuring the titer (amount of antibody present against a specific antigen) using measurements such as an ELISA or aggluttination assay. In this simple case a high enough level of antibody against the vaccine antigen is sufficient to predict protection. However antibody titer only evaluates one half of the function of antibody, which is dependent on both the variable region (Fv) to bind the antigen target, and the constant region (Fc) to elicit an effector response from other arms of the immune system. In the case of some diseases for which an effective vaccine has so far proven elusive, such as HIV, effector function has been shown to be an important driver of viral control in infected patients, and of protection in a vaccine setting.;The primary objective of this work is to establish a platform for the evaluation of polyclonal antibody samples, particularly of vaccine-induced antibodies, in a way that enables predictive modeling of a) effector activity, b) disease outcome/patient grouping and c) protection against infection. To this end we have developed a high throughput biophysical platform capable of evaluating many dimensions of the effector response simultaneously. Here we describe various aspects of this platform including its development, optimization and application for profiling clinical cohorts. |
