Back to Search
Start Over
A comparative immunogenicity study of HIV-1 virus-like particles bearing various forms of envelope proteins, particles bearing no envelope and soluble monomeric gp120
- Source :
-
Virology . Sep2007, Vol. 366 Issue 2, p245-262. 18p. - Publication Year :
- 2007
-
Abstract
- Abstract: 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. [Copyright &y& Elsevier]
- Subjects :
- *HIV
*BLOOD plasma
*IMMUNOGLOBULINS
*IMMUNE serums
Subjects
Details
- Language :
- English
- ISSN :
- 00426822
- Volume :
- 366
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Virology
- Publication Type :
- Academic Journal
- Accession number :
- 26568113
- Full Text :
- https://doi.org/10.1016/j.virol.2007.04.033