TY - JOUR
T1 - Interplay of diverse adjuvants and nanoparticle presentation of native-like HIV-1 envelope trimers
AU - Sliepen, Kwinten
AU - Schermer, Edith
AU - Bontjer, Ilja
AU - Burger, Judith A.
AU - Lévai, R. ka Felfödiné
AU - Mundsperger, Philipp
AU - Brouwer, Philip J. M.
AU - Tolazzi, Monica
AU - Farsang, Atilla
AU - Katinger, Dietmar
AU - Moore, John P.
AU - Scarlatti, Gabriella
AU - Shattock, Robin J.
AU - Sattentau, Quentin J.
AU - Sanders, Rogier W.
N1 - Funding Information: We thank Larry Liao and Bart Haynes for donating the DNA plasmid for generating ConS. We thank Hansi Dean, Wayne Koff, Joanne Stefano and Beth Rasmussen for their contributions to rabbit study C0119-15. We thank Marielle van Breemen for technical assistance. We thank Celia LaBranche and David Montefiori for providing neutralization assay data, shown in Supplementary Table 2 (previously published in11,56). This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 681137 (to R.J.S., R.W.S., G.S., D.K.). This work was also supported by the U.S. National Institutes of Health Grant P01 AI110657 (to J.P.M., R.W.S.); by the Bill and Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery (CAVD), grants OPP1111923, OPP1132237 and INV-002022 (to J.P.M., R.W.S.); R.W.S. is a recipient of a Vici grant from the Netherlands Organization for Scientific Research (NWO). Q.J.S. is a Jenner Investigator and a James Martin Senior Fellow. GS received a charitable donation from Fondation Dormeur, Vaduz, for instruments supporting the research of this study. Publisher Copyright: © 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85113579662&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41541-021-00364-x
DO - https://doi.org/10.1038/s41541-021-00364-x
M3 - Article
C2 - 34404812
SN - 1476-0584
VL - 6
JO - npj Vaccines
JF - npj Vaccines
IS - 1
M1 - 103
ER -