原创力文档cryoem visualization of an adenovirus capsid-incorporated hiv antigencryoem可视化的腺病毒capsid-incorporated艾滋病毒抗原.pdfVIP
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cryoem visualization of an adenovirus capsid-incorporated hiv antigencryoem可视化的腺病毒capsid-incorporated艾滋病毒抗原
CryoEM Visualization of an Adenovirus Capsid-
Incorporated HIV Antigen
1 1 2 2 3
Justin W. Flatt , Tara L. Fox , Natalia Makarova , Jerry L. Blackwell , Igor P. Dmitriev ,
3 3 1
Elena A. Kashentseva , David T. Curiel , Phoebe L. Stewart *
1 Department of Pharmacology and Cleveland Center for Membrane and Structural Biology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United
States of America, 2 Department of Medicine, Division of Infectious Diseases, Emory Vaccine Center and Yerkes National Primate Research Center, Emory University,
Atlanta, Georgia, United States of America, 3 Division of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri,
United States of America
Abstract
Adenoviral (Ad) vectors show promise as platforms for vaccine applications against infectious diseases including HIV.
However, the requirements for eliciting protective neutralizing antibody and cellular immune responses against HIV remain
a major challenge. In a novel approach to generate 2F5- and 4E10-like antibodies, we engineered an Ad vector with the HIV
membrane proximal ectodomain region (MPER) epitope displayed on the hypervariable region 2 (HVR2) of the viral hexon
capsid, instead of expressed as a transgene. The structure and flexibility of MPER epitopes, and the structural context of
these epitopes within viral vectors, play important roles in the induced host immune responses. In this regard,
understanding the critical factors for epitope presentation would facilitate optimization strategies for developing viral
vaccine vectors. Ther
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