The role of antibody function

Titer is a poor predictor of protection across differing vaccine regimens

The Systems Serology platform interrogates and explains humoral immune function, going beyond measures of antibody quantity (titer) and neutralization.

In vaccinology the dogma has been that high titers and neutralizing activity are sufficient for protection. It has become increasingly clear that this dogma is false, especially for pathogens that are hyper variable (such as HIV), have a complex lifecycle (such as malaria) or have evolved sophisticated immune evasion mechanisms (such as HSV). Developing vaccines to these targets as well as improving existing vaccines which are suboptimal, such as influenza or pertussis requires the application of much better insight into the functional quality of the antibody produced: this is what SeromYx provides.

Antibodies direct multiple complex mechanisms of immune destruction

Beyond titer and neutralization, antibodies mediate a complex array of mechanisms of immune destruction, of relevance not only to vaccine development but also to immunotherapies in infectious disease, cancer and autoimmunity. The importance of immune effector function such as antibody dependent cellular cytotoxicity (ADCC) or antibody-dependent cellular phagocytosis (ADCP) has been well understood by the developers of cancer therapies such as trastuzumab or obinutuzumab, but high throughput tools for screening for desired function have been lacking, until now.

Both the specific mechanisms and the degree of function elicited by a given antibody is determined by the interaction between the antibody and Fcγ receptors on innate immune cells and C1q, the recognition molecule of the complement system. In turn, this is determined by the antibody subclass and isotype and glycan structure of the Fc region of the antibody. Function is also modulated by the specific epitope on the target bound by the antibody. SeromYx platform can both measure function in an epitope dependent way, and tie it back to the specific structure of the antibody, shedding a unique insight on this complex interaction.

Effector function driven by antibody isotype and subclass and Fc glycan structure

updated: 1 year ago