Fc-Mediated Antibody Functions and Fc-Receptor Polymorphism

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Background

Antibodies (Ab) mediate protective functions against infectious agents by: (i) binding to pathogens and preventing their entry into target cells, referred to as neutralizing function, as well as (ii) facilitating the recruitment of Fc-receptor bearing cells that can eliminate pathogens or infected cells by mediating phagocytosis or cytotoxic activity, referred to as Fc-mediated functions. Antibodies can, therefore, be defined as neutralizing (nAb) and capable of mediating both functions, and non-neutralizing (non-nAb) restricted to Fc-mediated functions. Non-nAb have been previously reported to play a significant role in protection from a wide range of viral infections including Smallpox, Sindbis, Yellow Fever, Ebola and Influenza; as well as against non-viral infections such as Tuberculosis and Malaria. Interestingly, some non-nAb responses shown to protect against lethal alphavirus encephalitis are directed against epitopes present on the surface of infected cells, but not on virions. These findings suggest that this class of Abs may be distinct from those mediating neutralizing activities and could have a more variable epitope specificity.

Fc-mediated Ab functions can be elicited as a component of vaccine strategies, but may also be exploited in the development of monoclonal antibody (mAb) and mAb-based passive prophylaxis and/or immunotherapeutic regimens. Fc-mediated Ab functions rely on multiple mechanisms of action that include the recruitment of complement and Fc receptor-bearing cellular subsets that can mediate trogocytosis, phagocytosis, and cellular cytotoxicity. The interactions between Ab and complement or Fc receptor-bearing effector cells is influenced by multiple factors including host genetics such as Fc receptor polymorphisms; antibody isotypes, subclasses and glycoforms; and the phenotypic and molecular characteristics of effector cells. Some studies to investigate Fc-mediated function can be performed in small animal models, but others, such as the modeling of HIV-1 infection, require the utilization of non-human primates. Importantly however, the extent to which Fc-mediated functions are similar in humans and animal models remains incompletely described. This is due to the genotypic and phenotypic differences that exist among the species for both Ab Fc regions and Fc receptors. A special focus should be placed on the similarities and differences of species-related FcR phenotypes, that impact functional immunity, in order to fully translate pre-clinical observations into clinical studies.

In this Research Topic, we aim to gather a series of articles that address Fc-mediated Ab functions and the factors that influence them in both humans and in different mammalian species with a focus on how to use the animal models for vaccine and passive immunization pre-clinical trials. A particular focus will also be placed on the similarities and differences of species-related FcR phenotypes, that impact functional immunity, in order to fully translate pre-clinical observations into clinical studies.

Therefore, we seek articles that cover, but are not limited to, the following topics:

1. Role of Fc-mediated Ab functions against bacteria, virus, and parasitic infectious diseases.
2. Host genetic factors regulating and impacting Fc-mediated Ab functions.
3. Molecular mechanisms involved in Fc-Fc-receptor interactions.
4. Optimizing Fc-FcR interactions.
5. Animal models to investigate and predict outcome of Fc-mediated Ab responses.
6. Effector cells responsible for Fc-mediated Ab functions.

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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