• Alt, Frederick
• Landais, Elise
• Lu, Danny
• Mckenney, Katherine R.
• Baboo, Sabyasachi
• Skog, Patrick
• Alavi, Nushin
• Schief, William
• Sincomb, Troy
• Briney, Bryan
• Paulson, James
• Kubitz, Michael
• Kulp, Daniel
• Duan, Hongying
• Eskandarzadeh, Saman
• Hurtado, Jonathan
• Yates, John
• Willis, Jordan
• Lee, Jeong Hyun
• Flynn, Claudia T.
• Chen, Xuejun
• Himansu, Sunny
• Tingle, Ryan
• Cottrell, Christopher
• Kalyuzhniy, Oleksandr
• Mascola, John R.
• Liguori, Alessia
• Diedrich, Jolene
• Schiffner, Torben
• Luo, Sai

Abstract

<jats:p>A protective human immunodeficiency virus (HIV) vaccine will likely need to induce broadly neutralizing antibodies (bnAbs). Vaccination with the germline-targeting immunogen eOD-GT8 60mer adjuvanted with AS01<jats:sub>B</jats:sub>was found to induce VRC01-class bnAb precursors in 97% of vaccine recipients in the IAVI G001 phase 1 clinical trial; however, heterologous boost immunizations with antigens more similar to the native glycoprotein will be required to induce bnAbs. Therefore, we designed core-g28v2 60mer, a nanoparticle immunogen to be used as a first boost following eOD-GT8 60mer priming. We found, using a humanized mouse model approximating human conditions of VRC01-class precursor B cell diversity, affinity, and frequency, that both protein- and mRNA-based heterologous prime-boost regimens induced VRC01-class antibodies that gained key mutations and bound to near-native HIV envelope trimers lacking the N276 glycan. We further showed that VRC01-class antibodies induced by mRNA-based regimens could neutralize pseudoviruses lacking the N276 glycan. These results demonstrated that heterologous boosting can drive maturation toward VRC01-class bnAb development and supported the initiation of the IAVI G002 phase 1 trial testing mRNA-encoded nanoparticle prime-boost regimens.</jats:p>

Topics

• nanoparticle
• phase