High thermostability improves neutralizing antibody responses induced by native-like HIV-1 envelope trimers.
Journal
NPJ vaccines
ISSN: 2059-0105
Titre abrégé: NPJ Vaccines
Pays: England
ID NLM: 101699863
Informations de publication
Date de publication:
28 Feb 2022
28 Feb 2022
Historique:
received:
05
07
2021
accepted:
20
01
2022
entrez:
1
3
2022
pubmed:
2
3
2022
medline:
2
3
2022
Statut:
epublish
Résumé
Soluble HIV-1 envelope glycoprotein (Env) immunogens are a prime constituent of candidate vaccines designed to induce broadly neutralizing antibodies. Several lines of evidence suggest that enhancing Env immunogen thermostability can improve neutralizing antibody (NAb) responses. Here, we generated BG505 SOSIP.v9 trimers, which displayed virtually no reactivity with non-neutralizing antibodies and showed increased global and epitope thermostability, compared to previous BG505 SOSIP versions. Chemical crosslinking of BG505 SOSIP.v9 further increased the melting temperature to 91.3 °C, which is almost 25 °C higher than that of the prototype SOSIP.664 trimer. Next, we compared the immunogenicity of a palette of BG505-based SOSIP trimers with a gradient of thermostabilities in rabbits. We also included SOSIP.v9 proteins in which a strain-specific immunodominant epitope was masked by glycans to redirect the NAb response to other subdominant epitopes. We found that increased trimer thermostability correlated with increased potency and consistency of the autologous NAb response. Furthermore, glycan masking steered the NAb response to subdominant epitopes without decreasing the potency of the autologous NAb response. In summary, SOSIP.v9 trimers and their glycan masked versions represent an improved platform for HIV-1 Env based vaccination strategies.
Identifiants
pubmed: 35228534
doi: 10.1038/s41541-022-00446-4
pii: 10.1038/s41541-022-00446-4
pmc: PMC8885667
doi:
Types de publication
Journal Article
Langues
eng
Pagination
27Subventions
Organisme : Medical Research Council
ID : G0000635
Pays : United Kingdom
Organisme : NIAID NIH HHS
ID : P01 AI110657
Pays : United States
Organisme : Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
ID : P01AI110657
Organisme : Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)
ID : OPP1111923 and OPP1132237
Informations de copyright
© 2022. The Author(s).
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