Interplay of diverse adjuvants and nanoparticle presentation of native-like HIV-1 envelope trimers

Abstract The immunogenicity of HIV-1 envelope (Env) trimers is generally poor. We used the clinically relevant ConM SOSIP trimer to compare the ability of different adjuvants (squalene emulsion, ISCOMATRIX, GLA-LSQ, and MPLA liposomes) to support neutralizing antibody (NAb) responses in rabbits. The...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Kwinten Sliepen, Edith Schermer, Ilja Bontjer, Judith A. Burger, Réka Felfödiné Lévai, Philipp Mundsperger, Philip J. M. Brouwer, Monica Tolazzi, Atilla Farsang, Dietmar Katinger, John P. Moore, Gabriella Scarlatti, Robin J. Shattock, Quentin J. Sattentau, Rogier W. Sanders
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
Materias:
Acceso en línea:https://doaj.org/article/3493c21b5fee4dc2a902a4cfd21185c1
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
Descripción
Sumario:Abstract The immunogenicity of HIV-1 envelope (Env) trimers is generally poor. We used the clinically relevant ConM SOSIP trimer to compare the ability of different adjuvants (squalene emulsion, ISCOMATRIX, GLA-LSQ, and MPLA liposomes) to support neutralizing antibody (NAb) responses in rabbits. The trimers were administered as free proteins or on nanoparticles. The rank order for the adjuvants was ISCOMATRIX > SE > GLA-LSQ ~ MPLA liposomes > no adjuvant. Stronger NAb responses were elicited when the ConM SOSIP trimers were presented on ferritin nanoparticles. We also found that the GLA-LSQ adjuvant induced an unexpectedly strong antibody response to the ferritin core of the nanoparticles. This “off-target” effect may have compromised its ability to induce the more desired antitrimer antibodies. In summary, both adjuvants and nanoparticle display can improve the magnitude of the antibody response to SOSIP trimers but the best combination of trimer presentation and adjuvant can only be identified experimentally.