X Chen, D Missiakas*. Novel Antibody-Based Protection/Therapeutics in Staphylococcus aureus. Annu Rev Microbiol. 2024 Aug 15.

X Peng, J Chen, Y Gan, L Yang, Y Luo, C Bu, Y Huang, X Chen, J Tan, YY, Yang, P Yuan, X Ding.Biofunctional lipid nanoparticles for precision treatment and prophylaxis of bacterial infections. Sci Adv. 2024; 10(14): eadk9754.

Select pre-SZBL publications

X Chen, H Gula, T Pius, C Ou, M Gomozkova, LX Wang, O Schneewind, D Missiakas. Immunoglobulin G subclasses confer protection against Staphylococcus aureus bloodstream dissemination through distinct mechanisms in mouse models. PNAS, 2023, 120(14): e2220765120.

We find that protection with antibody targeting S. aureus is achieved in an FcγR-dependent manner in C57BL/6J mice and CR3-dependent manner in BALB/cJ mice. Protection was associated with the preferential expression of FcγRIV on C57BL/6J neutrophils and CR3 on BALB/cJ neutrophils. Thus, both the A/I FcγRs ratio and the relative abundance of FcγRs over CRs impact the effector activity of an antibody and the mechanism of elimination of immune complexes.

X Chen, O Schneewind, D Missiakas. Engineered human antibodies for the opsonization and killing of Staphylococcus aureus. PNAS, 2022, 119(4): e2114478119.

Anti-S. aureus antibodies that could promote decolonization, prevent infection, or treat disease would alleviate the selection for drug resistance. The successful development of such antibodies is complicated by Staphylococcal protein A (SpA) in the envelope of S. aureus. SpA captures immunoglobulins via their constant region, preventing antibodies from initiating anti-staphylococcal activities. Here, we demonstrate that therapeutic anti-S. aureus antibodies can be engineered to avoid sequestration by SpA. Such antibodies display extended half-lives and improve bacterial uptake and killing by immune cells including macrophages and neutrophils.

X Chen, M Shi, X Tong, HK Kim, LX Wang, O Schneewind, D Missiakas. Glycosylation-dependent opsonophagocytic activity of Staphylococcal protein A antibodies. PNAS, 2020, 117(37): 22992-23000. 

Recent studies have suggested that the glycosylation of antibody constant region is pivotal. We find that galactosylation of anti-S. aureus mAb that favors C1q recruitment is indispensable for opsonophagocytic killing of staphylococci and for protection against bloodstream infection in animals. The simple removal of fucosyl residues, which results in reduced C1q binding and increased engagement with FcγR, maintains the opsonophagocytic killing and protective attributes of the antibody. While the therapeutic benefit of monoclonal antibodies against infectious disease agents may be debatable, the functional characterization of such antibodies represents a powerful tool for the development of correlates of protection that may guide future vaccine trials.