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; Attila Farsang; Dietmar Katinger; John P Moore; Gabriella Scarlatti; Robin J Shattock; Quentin J Sattentau; Rogier W Sanders

doi:10.1038/s41541-021-00364-x

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

NPJ Vaccines. 2021 Aug 17;6(1):103. doi: 10.1038/s41541-021-00364-x.

Authors

Kwinten Sliepen¹, Edith Schermer¹, Ilja Bontjer¹, Judith A Burger¹, Réka Felfödiné Lévai², Philipp Mundsperger³, Philip J M Brouwer¹, Monica Tolazzi⁴, Attila Farsang², Dietmar Katinger³, John P Moore⁵, Gabriella Scarlatti⁴, Robin J Shattock⁶, Quentin J Sattentau⁷, Rogier W Sanders^{8

9}

Affiliations

¹ Department of Medical Microbiology, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
² Control Laboratory of Veterinary Medicinal Products and Animal Facility, Directorate of Veterinary Medicinal Products, National Food Chain Safety Office, Budapest, Hungary.
³ Polymun Scientific Immunbiologische Forschung GmbH, Klosterneuburg, Austria.
⁴ Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, Italy.
⁵ Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA.
⁶ Imperial College London, Department of Medicine, Division of Infectious Diseases, Section of Virology, Norfolk Place, London, W21PG, UK.
⁷ The Sir William Dunn School of Pathology, The University of Oxford, Oxford, OX13RE, UK.
⁸ Department of Medical Microbiology, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. [email protected].
⁹ Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, USA. [email protected].

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.

Abstract

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