The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies of exceptional breadth. MPER antibodies usually have long, hydrophobic CDRH3s, lack activity as inferred germline precursors, are often from the minor IgG3 subclass, and some are polyreactive, such as 4E10. Here we describe an MPER broadly neutralizing antibody from the major IgG1 subclass, PGZL1, which shares germline V/D-region genes with 4E10, has a shorter CDRH3, and is less polyreactive. A recombinant sublineage variant pan-neutralizes a 130-isolate panel at 1.4 μg/ml (IC50). Notably, a germline revertant with mature CDR3s neutralizes 12% of viruses and still binds MPER after DJ reversion. Crystal structures of lipid-bound PGZL1 variants and cryo-EM reconstruction of an Env-PGZL1 complex reveal how these antibodies recognize MPER and viral membrane. Discovery of common genetic and structural elements among MPER antibodies from different patients suggests that such antibodies could be elicited using carefully designed immunogens.

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Background:Glypican-3 (GPC3) has been widely recognized in the progression of liver tumors for several years. The relationship between overexpression of GPC3 and the poorer prognosis of patients with hepatocellular carcinoma (HCC) was performed by 2 meta-analyses. However, there were also some latest literatures that indicated different conclusions distinctly. It is necessary for us to carry out a meta-analysis by adding the latest data from current studies to explore the correlation between GPC3 and prognostic value in HCC.Methods:We conducted a meta-analysis including a total of 14 studies to assess the potential prognostic significance of GPC3 expression for overall survival (OS) and disease-free survival (DFS). The expression of GPC3 was assessed by immunohistochemistry.Results:Fourteen studies with 2364 patients were incorporated in the meta-analysis. The combined hazard ratios (HRs) revealed that the overexpression of GPC3 could forecast a poor OS [n = 2233 in 12 studies, HR = 1.40, 95% confidence interval (95% CI): 1.07–1.85, Z = 2.42, P = .02] and DFS (n = 1308 in 10 studies, HR = 1.61, 95% CI: 1.13–2.30, Z = 2.63, P = .008) in HCC patients. Subgroup treated by hepatectomy indicated that the pooled HR of OS was 1.43 (95% CI: 1.01–2.01, P = .04) and the combined HR of DFS was 1.59 (95% CI: 1.09–2.31, P = .02). The pooled odds ratios (ORs) showed that high GPC3 expression was also extensively associated with worse tumor differentiation, later tumor stage, presence of vascular invasion, and hepatitis B virus (HBV) infection. Subgroup analyses for GPC3 on HCC OS based on the studies categorized by regions, follow-up period, and sample size were also conducted.Conclusion:The meta-analysis indicated that overexpression of GPC3 was significantly associated with poor prognosis in patients with HCC.