Identification of a new epitope for HIV-neutralizing antibodies in the gp41 membrane proximal external region by an Env-tailored phage display library

作者: Torsten Meyer , Stefanie Koch , Joachim Koch , Hagen von Briesen , José M. Benito

DOI: 10.1002/EJI.201242974

关键词: Affinity maturationAntibodyMimotopePeptide libraryBiologyVirologyMonoclonal antibodyLinear epitopePhage displayMolecular biologyEpitope

摘要: HIV controllers are a valuable source for the identification of HIV-neutralizing antibodies, as chronic infection over decades allows extensive affinity maturation antibodies improved Ag recognition. We analyzed small cohort elite (ECs) using panel standardized HIV-1 pseudovirions on TZM-bl cells. An Env-tailored phage display library was generated to select epitopes targeted by neutralizing in EC26 plasma sample showing broadest activity. Selected Env fragments were mostly allocated membrane proximal external region gp41. After preabsorbing with selected EC26-2A4, we achieved 50% depletion its Furthermore, affinity-purified EC26-2A4 epitope from showed activity, proving that indeed contains an antibodies. Epitope fine mapping purified peptide arrays identified new overlapping, but clearly distinct, prominent 2F5 epitope. Of note, did not show autoreactivity cardiolipin, whereas low reactivity phosphatidylserine comparable mAb observed. Thus, this represents promising candidate further analysis view vaccine development.

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