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Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles.

Publication ,  Journal Article
Brouwer, PJM; Antanasijevic, A; de Gast, M; Allen, JD; Bijl, TPL; Yasmeen, A; Ravichandran, R; Burger, JA; Ozorowski, G; Torres, JL; Ringe, RP ...
Published in: NPJ Vaccines
February 9, 2021

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.

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Published In

NPJ Vaccines

DOI

EISSN

2059-0105

Publication Date

February 9, 2021

Volume

6

Issue

1

Start / End Page

24

Location

England

Related Subject Headings

  • 3207 Medical microbiology
  • 3204 Immunology
 

Citation

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Chicago
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MLA
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Brouwer, P. J. M., Antanasijevic, A., de Gast, M., Allen, J. D., Bijl, T. P. L., Yasmeen, A., … Sanders, R. W. (2021). Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles. NPJ Vaccines, 6(1), 24. https://doi.org/10.1038/s41541-021-00285-9
Brouwer, Philip J. M., Aleksandar Antanasijevic, Marlon de Gast, Joel D. Allen, Tom P. L. Bijl, Anila Yasmeen, Rashmi Ravichandran, et al. “Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles.NPJ Vaccines 6, no. 1 (February 9, 2021): 24. https://doi.org/10.1038/s41541-021-00285-9.
Brouwer PJM, Antanasijevic A, de Gast M, Allen JD, Bijl TPL, Yasmeen A, et al. Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles. NPJ Vaccines. 2021 Feb 9;6(1):24.
Brouwer, Philip J. M., et al. “Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles.NPJ Vaccines, vol. 6, no. 1, Feb. 2021, p. 24. Pubmed, doi:10.1038/s41541-021-00285-9.
Brouwer PJM, Antanasijevic A, de Gast M, Allen JD, Bijl TPL, Yasmeen A, Ravichandran R, Burger JA, Ozorowski G, Torres JL, LaBranche C, Montefiori DC, Ringe RP, van Gils MJ, Moore JP, Klasse PJ, Crispin M, King NP, Ward AB, Sanders RW. Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles. NPJ Vaccines. 2021 Feb 9;6(1):24.

Published In

NPJ Vaccines

DOI

EISSN

2059-0105

Publication Date

February 9, 2021

Volume

6

Issue

1

Start / End Page

24

Location

England

Related Subject Headings

  • 3207 Medical microbiology
  • 3204 Immunology