Immunological responses to influenza vaccination: lessons for improving vaccine efficacy

Abstract

A critical factor in the maturation of influenza vaccine responses is the nearly inevitable binding of vaccine antigens by exiting anti-influenza IgGs. These antigen-IgG immune complexes direct the response to immunization by modulating cellular processes that determine antibody and T-cell repertoires: maturation of dendritic cells, processing and presentation of antigens to T cells, trafficking of antigens to the germinal center, and selection of B cells for antibody production. By focusing on the recent advances in the study of the immunomodulatory processes mediated by IgG immune complexes upon influenza vaccination, we discuss a pathway that is critical for modulating the breadth and potency of anti-HA antibody responses and has previously led to the development of strategies to improve influenza vaccine efficacy.

Figure 1:. Structure and properties of Type I and Type II FcγRs. FcγRs are divided into two main types: Type I and II.

Despite their common property of interacting with the Fc domain of IgG antibodies, FcγR types present distinct structural and functional differences and have differential capacity to induce diverse immunomodulatory consequences that affect several aspects of immunity.

Figure 2:. Overview of the coordinated activity of Type I (FcγRIIb) and Type II (CD23) FcγRs in the regulation of B cell activation and selection.

Development of high-affinity IgG responses is determined by the activity of the CD23-FcγRIIb pathway. Engagement of CD23 by sialylated IgG immune complexes upregulates FcγRIIb expression on B cells, which in turn raises the threshold for the B-cell receptor (BCR)-mediated signaling and B-cell selection. Upon CD23 engagement, only B cells with high-affinity BCRs are selected due to the higher levels of FcγRIIb[20,28].