Structural and immunogenicity studies of a cleaved,stabilized envelope trimer derived from subtype A HIV-1 |
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Authors: | Yun Kang Sofija Andjelic James M. Binley Emma T. Crooks Michael Franti Sai Prasad N. Iyer Gerald P. Donovan Antu K. Dey Ping Zhu Kenneth H. Roux Robert J. Durso Thomas F. Parsons Paul J. Maddon John P. Moore William C. Olson |
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Affiliation: | 1. Progenics Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, United States;2. Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, United States;3. Department of Microbiology and Immunology, Weill Medical College of Cornell University, York Avenue, New York, NY 10021, United States;4. Department of Biological Science and Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306, United States |
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Abstract: | SOSIP gp140 trimers represent a soluble, stabilized, proteolytically cleaved form of the HIV-1 envelope (Env) glycoproteins. SOSIP gp140 derived from a subtype A HIV-1 isolate, KNH1144, forms exceptionally stable trimers that resemble virion-associated Env in antigenicity and topology. Here, we used electron microscopy to demonstrate that KNH1144 SOSIP gp140 trimers bound three soluble CD4 molecules in a symmetrical orientation similar to that seen for native Env. We compared the immunogenicities of KNH1144 SOSIP gp140 trimers and gp120 monomers in rabbits and found that the trimers were superior at eliciting neutralizing antibodies (NAbs) to homologous virus as well as neutralization-sensitive subtype B and C viruses. The NAb specificities for SOSIP antisera mapped in part to the CD4 binding site on gp120. We also observed adjuvant-dependent induction of antibodies to the residual levels of host cell proteins (HCPs) contained in the purified Env preparations. When present, HCP antibodies enhanced pseudovirus infection. Our findings are relevant for the further development of Env-based vaccines for HIV-1. |
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Keywords: | SOSIP gp140 KNH1144 Neutralizing antibody HIV-1 |
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