Immunoregulatory functions of immune complexes in vaccine and therapy

Abstract

Clinical and experimental preparations of IgG/soluble antigen complexes, as well as those formed following antibody therapy in vivo, are multifaceted immune regulators. These immune complexes (ICs) have been tested in humans and animal models, mostly in forms of experimental or clinical vaccination, for at least a century. With intensified research on Fcγ receptor‐mediated immune modulation, as well as with immune complex‐directed antigen processing, presentation, and inflammatory responses, there are renewed interests of using ICs in vaccines and immunotherapies. Currently, IC‐based immune therapy has been broadly experimented in HBV and HIV viral infection control and antitumor treatments. However, mechanistic insights of IC‐based treatments are relatively recent subjects of study; strong efforts are needed to establish links to connect laboratory findings with clinical practices. This review covers the history, mechanisms, and in vivo outcomes of this safe and effective therapeutic tool, with a clear aim to bridge laboratory findings with evolving clinical applications.

Neutrophils are essential for induction of vaccine-like effects by antiviral monoclonal antibody immunotherapies

“…Notably, in addition to antirespiratory syncytial virus (RSV) mAb used to treat infant respiratory disease, several mAbs directed against human cytomegalovirus, HIV, influenza, Ebola, and rabies virus are currently engaged in promising clinical trials (1,3,9,14). While the direct effects of antiviral mAbs on viral propagation have been studied extensively, little attention has been paid to their potential immunomodulatory effects until recently (10,15,16).…”

Codelivery of improved immune complex and virus-like particle vaccines containing Zika virus envelope domain III synergistically enhances immunogenicity

“…However, the weak immunogenicity of ZE3 must be overcome. Antigen incorporation into an immune complex is a proven method to strongly enhance B-cell and T-cell responses in the absence of adjuvant [26][27][28][29]. However, one drawback to the traditional RIC platform is that the antigenic fusion occurs between the N-terminus of the antigen and the C-terminus of the RIC antibody.…”

“…To circumvent this problem, recombinant immune complexes (RIC), which consist of an antibody fused to its cognate antigen, have also been explored as a vaccine platform due to their ability to form large antigen-antibody complexes that mimic those found during natural infection [22][23][24][25][26]. This complex formation results in a number of benefits including direct activation of antigen presenting cells via crosslinked Fcc receptors, enhancement of antigen presentation to B-cells, effective stimulation of immune responses through high avidity C1q binding, and increased T-cell activation [26][27][28][29].…”

Fcγ Receptor Function and the Design of Vaccination Strategies

“…Such functions include cellular activation and the release of chemokines and cytokines by innate effector leukocytes, antigen uptake, processing and presentation by antigen-presenting cells, regulation of B cell selection and IgG production, as well as modulation of T cell activation (Bournazos and Ravetch, 2015). Given the critical role of FcγR-mediated pathways to efficiently modulate adaptive immune responses, immune complex-based vaccination strategies have been previously employed to enhance the host immune responses against infectious agents and tumor antigens (Wen et al, 2016). Indeed, the concept of IgG-mediated enhancement of T-cell and antibody responses has been initially studied during the end of the 19 th century to enhance the immune responses against diphtheria (von Behring and Wernicke, 1892).…”