title: Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles
creator: Brouwer, Philip J. M.
creator: Antanasijevic, Aleksandar
creator: de Gast, Marlon
creator: Allen, Joel D
creator: Bijl, Tom P. L.
creator: Yasmeen, Anila
creator: Ravichandran, Rashmi
creator: Burger, Judith A.
creator: Ozorowski, Gabriel
creator: Torres, Jonathan L.
creator: LaBranche, Celia
creator: Montefiori, David C.
creator: Ringe, Rajesh P.
creator: Van Gils, Marit J.
creator: Moore, John P.
creator: Klasse, Per Johan
creator: Crispin, Max
creator: King, Neil P.
creator: Ward, Andrew B.
creator: Sanders, Rogier W.
subject: QR180 Immunology
description: The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically relevant, neutralization-resistant (Tier-2) HIV-1 strains. Multivalent antigen presentation on nanoparticles is an established strategy to increase vaccine-driven immune responses. However, due to nanoparticle instability in vivo, the display of non-native Env structures, and the inaccessibility of many neutralizing antibody (NAb) epitopes, the effects of nanoparticle display are generally modest for Env trimers. Here, we generate two-component self-assembling protein nanoparticles presenting twenty SOSIP trimers of the clade C Tier-2 genotype 16055. We show in a rabbit immunization study that these nanoparticles induce 60-fold higher autologous Tier-2 NAb titers than the corresponding SOSIP trimers. Epitope mapping studies reveal that the presentation of 16055 SOSIP trimers on these nanoparticle focuses antibody responses to an immunodominant apical epitope. Thus, these nanoparticles are a promising platform to improve the immunogenicity of Env trimers with apex-proximate NAb epitopes.
publisher: Nature Research
date: 2021-02-09
type: Article
type: PeerReviewed
relation: https://www.nature.com/articles/s41541-021-00285-9
identifier:   Brouwer, Philip J. M. and Antanasijevic, Aleksandar and de Gast, Marlon and Allen, Joel D and Bijl, Tom P. L. and Yasmeen, Anila and Ravichandran, Rashmi and Burger, Judith A. and Ozorowski, Gabriel and Torres, Jonathan L. and LaBranche, Celia and Montefiori, David C. and Ringe, Rajesh P. and Van Gils, Marit J. and Moore, John P. and Klasse, Per Johan and Crispin, Max and King, Neil P. and Ward, Andrew B. and Sanders, Rogier W.  (2021) Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles.  NPJ VACCINES, 6 (1).  pp. 1-24.      
relation: http://crdd.osdd.net/open/2664/