Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
A comparative immunogenicity study of HIV-1 virus-like particles bearing various forms of envelope proteins, particles bearing no envelope and soluble monomeric gp120
Virology, Volume 366, No. 2, Year 2007
Notification
URL copied to clipboard!
Description
To assess the potential of native Envelope glycoprotein (Env) trimers as neutralizing antibody vaccines, we immunized guinea pigs with three types of VLPs and soluble gp120. Particles included "SOS-VLPs" (bearing disulfide-shackled functional trimers), "UNC-VLPs" (bearing uncleaved nonfunctional Env) and "naked VLPs" (bearing no Env). The SOS-VLPs were found to have a density of about 27 native trimers per particle, approximately twice that of live inactivated HIV-1 preparations. As immunogens, UNC- and SOS-VLP rapidly elicited anti-gp120 antibodies focused on the V3 loop and the gp120 coreceptor binding site. Reactivity to the gp41 immunodominant domain was absent in SOS-VLP sera, presumably because gp120-gp41 association is stabilized, effectively covering this epitope. Gp120-immune sera reacted with the receptor binding sites of gp120 and were less focused on the V3 loop. Some Env-VLP sera neutralized primary isolates at modest titers. The measurement of neutralization was found to be affected by the cell lines used. Depending on the assay particulars, non-Env specific antibodies in VLP sera could enhance infection, or nonspecifically neutralize. However, a neutralization assay using TZM-BL cells was essentially clear of these effects. We also describe a native trimer binding assay to confirm neutralization activity in a manner that completely eliminates nonspecific effects. Overall, our data suggests that Env-VLP sera were primarily focused on nonfunctional forms of Env on VLP surfaces, possibly gp120/gp41 monomers and not the trimers. Therefore, to make progress toward a more effective VLP-based vaccine, we will need to find ways to refocus the attention of B cells on native trimers. © 2007 Elsevier Inc. All rights reserved.
Authors & Co-Authors
Crooks, Emma T.
United States, San Diego
Torrey Pines Institute for Molecular Studies
Moore, Penny L.
South Africa, Johannesburg
National Institute for Communicable Diseases
Franti, Michael
United States, Bedford
Lantheus
Cayanan, Charmagne S.
United States, San Diego
Scripps Research Institute
Zhu, Ping
United States, Tallahassee
Florida State University
Jiang, Pengfei
United States, San Diego
Torrey Pines Institute for Molecular Studies
de Vries, Robbert P.
United States, San Diego
Torrey Pines Institute for Molecular Studies
Netherlands, Amsterdam
Universiteit Van Amsterdam
Wiley, Cheryl
United States, San Diego
Scripps Research Institute
Zharkikh, Irina
United States, San Diego
Scripps Research Institute
Schülke, Norbert
United States, Cambridge
Takeda Oncology
Roux, Kenneth H.
United States, Tallahassee
Florida State University
Montefiori, David Charles
United States, Durham
Duke University
Burton, Dennis Raymond
United States, San Diego
Scripps Research Institute
Binley, James M.
United States, San Diego
Torrey Pines Institute for Molecular Studies
Statistics
Citations: 131
Authors: 14
Affiliations: 8
Identifiers
Doi:
10.1016/j.virol.2007.04.033
ISSN:
00426822
e-ISSN:
10960341
Research Areas
Infectious Diseases
Study Locations
Guinea