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

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 antige...

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Bibliographic Details
Published in:npj vaccines 2021-02, Vol.6 (1), p.24-14, Article 24
Main Authors: Brouwer, Philip J. M., Antanasijevic, Aleksandar, de Gast, Marlon, Allen, Joel D., Bijl, Tom P. L., Yasmeen, Anila, Ravichandran, Rashmi, Burger, Judith A., Ozorowski, Gabriel, Torres, Jonathan L., LaBranche, Celia, Montefiori, David C., Ringe, Rajesh P., van Gils, Marit J., Moore, John P., Klasse, Per Johan, Crispin, Max, King, Neil P., Ward, Andrew B., Sanders, Rogier W.
Format: Article
Language:English
Subjects:
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Antibodies
Biomedical and Life Sciences
Biomedicine
Glycoproteins
HIV
Human immunodeficiency virus
Immunization
Immunogenicity
Infectious Diseases
Medical Microbiology
Nanoparticles
Neutralization
Public Health
Vaccine
Vaccines
Virology
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Summary: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.
ISSN:2059-0105
2059-0105
DOI:10.1038/s41541-021-00285-9