Antibody Function

The Many Roles of Antibodies Beyond Neutralization

Antibody Function

The Many Roles of Antibodies Beyond Neutralization

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

Neutralization Activity

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 difficult vaccine targets because 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). 

 

Titer is a poor predictor of protection across differing vaccine regimens

Developing vaccines to these targets as well as improving existing vaccines which are suboptimal, such as influenza or pertussis, requires much better insight into the functional quality of the antibody produced: this insight is what SeromYx provides.

The Importance of Immune Effector Functions

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. 

Antibodies direct multiple complex mechanisms of immune destruction

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.

Multiple Factors Modulate Function

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. 

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

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.

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