Structural and immunogenicity studies of a cleaved, stabilized envelope trimer derived from subtype A HIV-1.

TitleStructural and immunogenicity studies of a cleaved, stabilized envelope trimer derived from subtype A HIV-1.
Publication TypeJournal Article
Year of Publication2009
AuthorsKang YKenneth, Andjelic S, Binley JM, Crooks ET, Franti M, Iyer SPrasad N, Donovan GP, Dey AK, Zhu P, Roux KH, Durso RJ, Parsons TF, Maddon PJ, Moore JP, Olson WC
Date Published2009 Aug 13
KeywordsAnimals, Antibodies, Monoclonal, Antigen-Antibody Complex, Antigens, CD4, Cell Line, env Gene Products, Human Immunodeficiency Virus, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, HIV Antibodies, HIV Envelope Protein gp120, HIV-1, Humans, Microscopy, Electron, Models, Molecular, Neutralization Tests, Protein Structure, Quaternary, Rabbits

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.

Alternate JournalVaccine
PubMed ID19567243
Grant ListN01 AI30030 / AI / NIAID NIH HHS / United States

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