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

Kwinten Sliepen,Ilja Bontjer,Monica Tolazzi,Quentin J Sattentau,Edith Schermer,Robin J Shattock,Gabriella Scarlatti,Réka Felfödiné Lévai,John P Moore,Dietmar Katinger,Philipp Mundsperger,Philip J M Brouwer,Rogier W Sanders,Judith A Burger,Attila Farsang

doi:10.1038/s41541-021-00364-x

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.

Highlights

The need for an HIV-1 vaccine is undebated but formidable scientific challenges have hampered the development of a vaccine
Neutralizing antibodies (NAb) responses correlate with protection for many licensed antiviral vaccines[1] but HIV-1 NAbs have been difficult to induce by vaccination
The induction of NAb responses against relatively neutralization-resistant (Tier 2) viruses by vaccination was facilitated by the design of stable soluble mimics of the native Env trimer, such as BG505 SOSIP.6644

Summary

INTRODUCTION

The need for an HIV-1 vaccine is undebated but formidable scientific challenges have hampered the development of a vaccine. The induction of NAb responses against relatively neutralization-resistant (Tier 2) viruses by vaccination was facilitated by the design of stable soluble mimics of the native Env trimer, such as BG505 SOSIP.6644. ConM SOSIP.v7 induces strong NAb responses against artificial consensus-based viruses. These NAb responses target the trimer apex, an epitope that might be an appropriate vaccine component to drive neutralization breadth[11]. Some immunization studies suggest that Freund’s core and the NAb response against HIV-1 Together, these results adjuvant can denature antigens and open up cryptic epitopes that might be useful for selecting the optimal adjuvant for the are irrelevant for inducing NAbs[29,30].

Study design

DISCUSSION

Findings

METHODS