Molecular properties of human IgG subclasses and their implications for designing therapeutic monoclonal antibodies against infectious diseases

Abstract

Monoclonal antibodies are being developed as therapeutics to complement drugs and vaccines or to fill the gap where no drugs or vaccines exist. These therapeutic antibodies (ThAb) may be especially important for infectious diseases in which there is antibiotic resistance, toxin-mediated pathogenesis, or for emerging pathogens. The unique structure of antibodies determines the specific nature of the effector function, so when developing ThAb, the desired effector functions need to be considered and integrated into the design and development processes to ensure maximum efficacy and safety. Antibody subclass is a critical consideration, but it is noteworthy that almost all ThAb that are licenced or currently in development utilise an IgG1 backbone. This review outlines the major structural properties that vary across subclasses, how these properties affect functional immunity, and discusses the various approaches used to study subclass responses to infectious diseases. We also review the factors associated with the selection of antibody subclasses when designing ThAb and highlight circumstances where different subclass properties might be beneficial when applied to particular infectious diseases. These approaches are critical to the future design of ThAb and to the study of naturally-acquired and vaccine-induced immunity.

Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis

“…However, because abundance of subclasses was not overtly different in antibodies isolated from protective or nonprotective donors (Fig. S2B) and because the half-life of IgG3 from all four donors tested at ∼4 d was in keeping with previous studies (32,33), it is not clear if this finding was relevant to the protection in the in vivo model.…”

“…3) strongly argues against the observed phenotype being because of the potential immunomodulatory effect of passive immunization with pooled Ig that had been previously reported (14). The Ig subclass may have important implications for the nature of immune function (23,32). The abundance of IgG3 from protective donors, which is associated with increased activity (32), was higher at days 1 and 3 than that from a nonprotective donor when testing for decay kinetics in the mouse model (Fig.…”

“…The Ig subclass may have important implications for the nature of immune function (23,32). The abundance of IgG3 from protective donors, which is associated with increased activity (32), was higher at days 1 and 3 than that from a nonprotective donor when testing for decay kinetics in the mouse model (Fig. S2A).…”

Effect of β-glucan Supplementation on Levels of IgM, IgA, IgG and Its Subclasses IgG1, IgG2, IgG3, and IgG4 in Cancer Patients

“…We expected that possible changes in subgroups levels might be connected with the risk of development of frequent respiratory diseases. It is known that the decrease in IgG1 levels might result in the risk of loss of a capacity to bind soluble antigens and membrane proteins, to modulate reactivity of polysaccharide antigens, to bind via Fc receptors on macrophages and to activate complement [4] .…”

“…Abnormal levels of IgG1 are often found in patients with reoccurring respiratory diseases [6] and in patients with risk of atopia or autoimmune diseases. The fact that molecular properties of individual IgG subclasses participated in the treatment of several diseases including infectious diseases is well established [4] . Detailed evaluation of antibody response of individual subclasses together with evaluation of the presence of β-glucan helps in early diagnosis of candidiasis [7] .…”