The role of IgG Fc receptors in antibody-dependent enhancement

@article{Bournazos2020TheRO,
  title={The role of IgG Fc receptors in antibody-dependent enhancement},
  author={Stylianos Bournazos and Aaron Gupta and Jeffrey V. Ravetch},
  journal={Nature Reviews. Immunology},
  year={2020},
  pages={1 - 11}
}
Antibody-dependent enhancement (ADE) is a mechanism by which the pathogenesis of certain viral infections is enhanced in the presence of sub-neutralizing or cross-reactive non-neutralizing antiviral antibodies. In vitro modelling of ADE has attributed enhanced pathogenesis to Fcγ receptor (FcγR)-mediated viral entry, rather than canonical viral receptor-mediated entry. However, the putative FcγR-dependent mechanisms of ADE overlap with the role of these receptors in mediating antiviral… Expand
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References

SHOWING 1-10 OF 241 REFERENCES
In Vivo Assessment of Antibody-Dependent Enhancement of Influenza B Infection.
TLDR
The results demonstrate that MHAB5553A across a broad range of doses did not enhance primary influenza B infection or disease in this model, and represent a nonclinical de-risking of the ADE potential with this antibody. Expand
Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infection
TLDR
Using convalescent sera from dengue patients, it is observed that neutralization of the homologous serotypes occurred despite FcγR-mediated uptake, and it is demonstrated that this inhibition occurred through the formation of viral aggregates by antibodies in a concentration-dependent manner. Expand
Epitope specificity plays a critical role in regulating antibody-dependent cell-mediated cytotoxicity against influenza A virus
TLDR
The data demonstrate that antibody specificity plays an important role in the regulation of ADCC, and that cross-talk among antibodies of varying specificities determines the magnitude of Fc receptor-mediated effector functions. Expand
Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry
TLDR
A neutralizing monoclonal antibody, which targets the receptor-binding domain of Middle East respiratory syndrome (MERS) coronavirus spike, mediates viral entry using pseudovirus entry and biochemical assays, and results showed that MAb binds to the virus surface spike, allowing it to undergo conformational changes and become prone to proteolytic activation. Expand
Monoclonal antibody-mediated enhancement of dengue virus infection in vitro and in vivo and strategies for prevention
TLDR
It is confirmed that significant viral amplification could occur during DENV infections in humans with prior infection or with maternally transferred immunity, possibly leading to severe dengue. Expand
A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus.
TLDR
Antibody-mediated effector functions, including phagocytosis and NK cell activation, were associated with protection, particularly for antibodies with moderate neutralizing activity, and this framework identifies functional correlates that can inform therapeutic and vaccine design strategies against EBOV and other pathogens. Expand
Antibody-Dependent Enhancement of Ebola Virus Infection by Human Antibodies Isolated from Survivors.
TLDR
Mutations of Fc fragments of an mAb that altered its interaction with Fc receptors rendered the antibody partially protective in vivo at a low dose, suggesting that ADE counteracts antibody-mediated protection and facilitates dissemination of filovirus infections. Expand
Broadly Neutralizing Anti-HIV-1 Antibodies Require Fc Effector Functions for In Vivo Activity
TLDR
Assessment of the in-vivo activity of several broadly neutralizing antibodies against HIV-1 revealed that FcγR-mediated effector function contributes substantially to their capacity to block viral entry, suppress viremia, and confer therapeutic activity. Expand
Differential requirements for FcγR engagement by protective antibodies against Ebola virus
TLDR
It is found that anti-EBOV antibodies exhibit differential requirements for FcγR engagement in mediating their protective activity independent of their distance from the viral membrane, guiding the design of optimized antibody-based therapeutics with maximal protective efficacy. Expand
Optimal activation of Fc-mediated effector functions by influenza virus hemagglutinin antibodies requires two points of contact
TLDR
It is demonstrated that the receptor-binding domain of the HA is required to bind to sialic acid expressed on the surface of effector cells to optimize effector cell activation, and this finding provides a basic understanding of how an optimal antibody-dependent cell-mediated response against influenza virus is achieved and may allow for better vaccine design. Expand
...
1
2
3
4
5
...