Fcγ Receptor Function and the Design of Vaccination Strategies

Bournazos, Stylianos; Ravetch, Jeffrey V.

doi:10.1016/j.immuni.2017.07.009

Cited by 156 publications

(169 citation statements)

References 101 publications

(167 reference statements)

Supporting

Mentioning

169

Contrasting

Order By: Relevance

“…The activities of Fc␥Rs can regulate B cell selection and IgG affinity maturation, such as the demonstrated effects of Fc␥RIIb expression on B cell signaling (1). Moreover, susceptibility to autoimmune diseases, such as systemic lupus erythematosus, has been linked to differential expression of functional Fc␥RIIb, driven by genetic variations in the FCGR2B promoters (54,55), Fc␥R copy number variation (56), or amino acid changes in Fc␥RIIb (57).…”

Section: Discussionmentioning

confidence: 99%

“…KEYWORDS Fc gamma receptor, HIV/AIDS vaccine trial, HVTN 505, genetic polymorphisms F c gamma receptors (Fc␥Rs) are expressed on the leukocyte surface and interact with the Fc domain of immunoglobulin G (IgG) antibodies. Interaction of Fc␥Rs with IgG immune complexes initiates intracellular signaling pathways that lead to a variety of downstream events, including cellular activation and cytokine/chemokine production (1,2). These events can have either immunostimulatory or immunosuppressive effects, making Fc␥Rs major players that modulate a range of processes, including antibody production, antigen presentation, and activation of B cells and innate immune effector cells (3).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Fc Gamma Receptor Polymorphisms Modulated the Vaccine Effect on HIV-1 Risk in the HVTN 505 HIV Vaccine Trial

Gilbert

Carpp

et al. 2019

J Virol

View full text Add to dashboard Cite

HIV Vaccine Trials Network (HVTN) 505 was a phase 2b efficacy trial of a DNA/recombinant adenovirus 5 (rAd5) HIV vaccine regimen. Although the trial was stopped early for lack of overall efficacy, later correlates of risk and sieve analyses generated the hypothesis that the DNA/rAd5 vaccine regimen protected some vaccinees from HIV infection yet enhanced HIV infection risk for others. Here, we assessed whether and how host Fc gamma receptor (Fc␥R) genetic variations influenced the DNA/rAd5 vaccine regimen's effect on HIV infection risk. We found that vaccine receipt significantly increased HIV acquisition compared with placebo receipt among participants carrying the FCGR2C-TATA haplotype (comprising minor alleles of four FCGR2C single-nucleotide polymorphism [SNP] sites) (hazard ratio [HR] ϭ 9.79, P ϭ 0.035) but not among participants without the haplotype (HR ϭ 0.86, P ϭ 0.67); the interaction of vaccine and haplotype effect was significant (P ϭ 0.034). Similarly, vaccine receipt increased HIV acquisition compared with placebo receipt among participants carrying the FCGR3B-AGA haplotype (comprising minor alleles of the 3 FCGR3B SNPs) (HR ϭ 2.78, P ϭ 0.058) but not among participants without the haplotype (HR ϭ 0.73, P ϭ 0.44); again, the interaction of vaccine and haplotype was significant (P ϭ 0.047). The FCGR3B-AGA haplotype also influenced whether a combined Env-specific CD8 ϩ T-cell polyfunctionality score and IgG response correlated significantly with HIV risk; an FCGR2A SNP and two FCGR2B SNPs influenced whether anti-gp140 antibody-dependent cellular phagocytosis correlated significantly with HIV risk. These results provide further evidence that Fc gamma receptor genetic variations may modulate HIV vaccine effects and immune function after HIV vaccination.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Fc Gamma Receptor Polymorphisms Modulated the Vaccine Effect on HIV-1 Risk in the HVTN 505 HIV Vaccine Trial

Gilbert

Carpp

et al. 2019

J Virol

View full text Add to dashboard Cite

show abstract

“…[10][11][12][13][14] A major factor that contribute to the structural and functional diversity of glycoconjugates is their sialic acids capping. [15][16][17] Here we discuss diverse aspects of sialic acids biology and their implications on human-specific immune responses during health, disease, and xenotransplantation.…”

mentioning

confidence: 99%

Evolution of sialic acids: Implications in xenotransplant biology

Paul

Padler‐Karavani

2018

Xenotransplantation

View full text Add to dashboard Cite

All living cells are covered with a dense "sugar-coat" of carbohydrate chains (glycans) conjugated to proteins and lipids. The cell surface glycome is determined by a non-template driven process related to the collection of enzymes that assemble glycans in a sequential manner. In mammals, many of these glycans are topped with sialic acids (Sia), a large family of acidic sugars. The "Sialome" is highly diverse owing to various Sia types, linkage to underlying glycans, range of carriers, and complex spatial organization. Presented at the front of cells, Sia play a major role in immunity and recognition of "self" versus "non-self," largely mediated by the siglecs family of Sia-binding host receptors. Albeit many mammalian pathogens have evolved to hijack this recognition system to avoid host immune attack, presenting a fascinating host-pathogen evolutionary arms race. Similarly, cancer cells exploit Sia for their own survival and propagation. As part of this ongoing fitness, humans lost the ability to synthesize the Sia type N-glycolylneuraminic acid (Neu5Gc), in contrast to other mammals. While this loss had provided an advantage against certain pathogens, humans are continuously exposed to Neu5Gc through mammalian-derived diet (eg, red meat), consequently generating a complex immune response against it. Circulating anti-Neu5Gc antibodies together with Neu5Gc on some human tissues mediate chronic inflammation "xenosialitis" that exacerbate various human diseases (eg, cancer and atherosclerosis). Similarly, Neu5Gc-containing xenografts are exposed to human anti-Neu5Gc antibodies with implications to sustainability. This review aimed to provide a glimpse into the evolution of Sia and their implications to xenotransplantation.

show abstract

“…Extracellular engagement of classical transmembrane-bound Fc receptors results in intracellular activation or inhibitory signal transduction (51,52). Their regulation is dependent upon factors such as expression level, receptor cross-linking and the ratio between activating and inhibitory receptors, which together set the activation threshold.…”

Section: Regulation Of Trim21 Immune Signalingmentioning

confidence: 99%

TRIM21—From Intracellular Immunity to Therapy

et al. 2019

View full text Add to dashboard Cite

Tripartite motif containing-21 (TRIM21) is a cytosolic ubiquitin ligase and antibody receptor that provides a last line of defense against invading viruses. It does so by acting as a sensor that intercepts antibody-coated viruses that have evaded extracellular neutralization and breached the cell membrane. Upon engagement of the Fc of antibodies bound to viruses, TRIM21 triggers a coordinated effector and signaling response that prevents viral replication while at the same time inducing an anti-viral cellular state. This dual effector function is tightly regulated by auto-ubiquitination and phosphorylation. Therapeutically, TRIM21 has been shown to be detrimental in adenovirus based gene therapy, while it may be favorably utilized to prevent tau aggregation in neurodegenerative disorders. In addition, TRIM21 may synergize with the complement system to block viral replication as well as transgene expression. TRIM21 can also be utilized as a research tool to deplete specific proteins in cells and zebrafish embryos. Here, we review our current biological understanding of TRIM21 in light of its versatile functions.

show abstract

Fcγ Receptor Function and the Design of Vaccination Strategies

Cited by 156 publications

References 101 publications

Fc Gamma Receptor Polymorphisms Modulated the Vaccine Effect on HIV-1 Risk in the HVTN 505 HIV Vaccine Trial

Fc Gamma Receptor Polymorphisms Modulated the Vaccine Effect on HIV-1 Risk in the HVTN 505 HIV Vaccine Trial

Evolution of sialic acids: Implications in xenotransplant biology

TRIM21—From Intracellular Immunity to Therapy

Contact Info

Product

Resources

About