Interplay of diverse adjuvants and nanoparticle presentation of native-like HIV-1 envelope trimers
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
Affiliations
Kwinten Sliepen
Department of Medical Microbiology, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam
Edith Schermer
Department of Medical Microbiology, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam
Ilja Bontjer
Department of Medical Microbiology, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam
Judith A. Burger
Department of Medical Microbiology, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam
Réka Felfödiné Lévai
Control Laboratory of Veterinary Medicinal Products and Animal Facility, Directorate of Veterinary Medicinal Products, National Food Chain Safety Office
Department of Medical Microbiology, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam
Monica Tolazzi
Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele
Atilla Farsang
Control Laboratory of Veterinary Medicinal Products and Animal Facility, Directorate of Veterinary Medicinal Products, National Food Chain Safety Office
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.
