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Neutralizing Antibody Induction by HIV-1 Envelope Glycoprotein SOSIP Trimers on Iron Oxide Nanoparticles May Be Impaired by Mannose Binding Lectin.

Authors :
Ringe, Rajesh P.
Cruz Portillo, Victor M.
Dosenovic, Pia
Ketas, Thomas J.
Ozorowski, Gabriel
Nogal, Bartek
Perez, Lautaro
LaBranche, Celia C.
Jillian Lim
Francomano, Erik
Wilson, Ian A.
Sanders, Rogier W.
Ward, Andrew B.
Montefiori, David C.
Nussenzweig, Michel C.
Klasse, P. J.
Cupo, Albert
Moore, John P.
Source :
Journal of Virology. Mar2020, Vol. 94 Issue 6, p1-32. 32p.
Publication Year :
2020

Abstract

We covalently attached human immunodeficiency virus type 1 (HIV-1) Env SOSIP trimers to iron oxide nanoparticles (IO-NPs) to create a particulate immunogen for neutralizing antibody (NAb) induction. The attached trimers, ∼20 per particle, retained native-like antigenicity, judged by reactivity with NAbs and non-NAbs. Bivalent (BG505 and B41) trimer IO-NPs were made, as were IO-NPs displaying B41 trimers carrying a PADRE T-cell helper epitope (TCHE). We immunized mice with B41 soluble or IO-NP trimers after PADRE peptide priming. After two immunizations, IO-NP presentation and the TCHE tag independently and substantially increased anti-trimer antibody responses, but titer differences waned after two further doses. Notable and unexpected findings were that autologous NAbs to the N289 glycan hole epitope were consistently induced in mice given soluble but not IO-NP trimers. Various recombinant mannose binding lectins (MBLs) and MBLs in sera of both murine and human origin bound to soluble and IO-NP trimers. MBL binding occluded the autologous NAb epitope on the B41 IO-NP trimers, which may contribute to its poor immunogenicity. The exposure of a subset of broadly active NAb epitopes was also impaired by MBL binding, which could have substantial implications for the utility of trimer-bearing nanoparticles in general and perhaps also for soluble Env proteins. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0022538X
Volume :
94
Issue :
6
Database :
Academic Search Index
Journal :
Journal of Virology
Publication Type :
Academic Journal
Accession number :
142071462
Full Text :
https://doi.org/10.1128/JVI.01883-19