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

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 similar to 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.

Automated summary

The study showed that ISCOMATRIX was the most effective adjuvant, while GLA-LSQ adjuvant unexpectedly induced strong antibody response, though it may compromise the production of more desired anti-trimer antibodies due to an off-target effect. Both adjuvants and nanoparticle display can enhance the antibody response to SOSIP trimers, but the optimal combination requires experimental identification.