7cn2
Subparticle refinement of human papillomavirus type 16 pesudovirus in complex with H16.001 Fab
Structural highlights
FunctionVL1_HPV16 Forms an icosahedral capsid with a T=7 symmetry and a 50 nm diameter. The capsid is composed of 72 pentamers linked to each other by disulfide bonds and associated with L2 proteins. Binds to heparan sulfate proteoglycans on cell surface of basal layer keratinocytes to provide initial virion attachment. This binding mediates a conformational change in the virus capsid that facilitates efficient infection. The virion enters the host cell via endocytosis. During virus trafficking, L1 protein dissociates from the viral DNA and the genomic DNA is released to the host nucleus. The virion assembly takes place within the cell nucleus. Encapsulates the genomic DNA together with protein L2.[HAMAP-Rule:MF_04002][1] [2] [3] Publication Abstract from PubMedWith more human papillomavirus (HPV) virus-like particle (VLP) vaccines to hit the market in future, a monoclonal antibody (mAb) with preferably comparable reactivity against vaccines from different expression systems and bioprocesses is urgently needed for the potency characterization. Among all mAbs against HPV16 collected, rabbit mAb H16.001 is potently neutralizing with the highest affinity, recognizes an immune-dominant epitope, and can comparably react with HPV16 vaccines from various sources. Cryo-electron microscopic (cryo-EM) structure demonstrated that 360 H16.001 Fabs could bind to HPV16 capsid in preferable binding manner without steric hindrance between neighboring Fabs, potentially supporting its identification for VLP structural integrity and utility in monitoring VLP structural probity. This structural analysis indicated that mAb H16.001 afforded unbiased potency characterization for various HPV16 vaccines and was potential for use in vaccine regulation practice. This study also showed a model process for selecting suitable mAbs for potency assays of other vaccines. Structural characterization of a neutralizing mAb H16.001, a potent candidate for a common potency assay for various HPV16 VLPs.,Huang W, He M, Ning T, Nie J, Zhang F, Zheng Q, Zhang R, Xu Y, Gu Y, Li S, Wang Y NPJ Vaccines. 2020 Sep 23;5:89. doi: 10.1038/s41541-020-00236-w. eCollection , 2020. PMID:33042588[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||
