1. Long trimer-immunization interval and appropriate adjuvant reduce immune responses to the soluble HIV-1-envelope trimer base
- Author
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Duan, H, Corrigan, AR, Cheng, C, Biju, A, Gonelli, CA, Olia, AS, Teng, I-T, Xu, K, O'Dell, S, Narpala, S, Castro, M, Serebryannyy, L, Wang, J, Parchment, DK, Sarfo, EK, van Schooten, J, Todd, J-P, Wang, S, Harris, DR, Geng, H, Jafari, AJ, Program, VRCP, Woodward, RA, Doria-Rose, NA, Foulds, KE, Mcdermott, AB, Gils, MJV, Koup, RA, Pierson, TC, Kwong, PD, Mascola, JR, Duan, H, Corrigan, AR, Cheng, C, Biju, A, Gonelli, CA, Olia, AS, Teng, I-T, Xu, K, O'Dell, S, Narpala, S, Castro, M, Serebryannyy, L, Wang, J, Parchment, DK, Sarfo, EK, van Schooten, J, Todd, J-P, Wang, S, Harris, DR, Geng, H, Jafari, AJ, Program, VRCP, Woodward, RA, Doria-Rose, NA, Foulds, KE, Mcdermott, AB, Gils, MJV, Koup, RA, Pierson, TC, Kwong, PD, and Mascola, JR
- Abstract
Soluble 'SOSIP'-stabilized HIV-1 envelope glycoprotein (Env) trimers elicit dominant antibody responses targeting their glycan-free base regions, potentially diminishing neutralizing responses. Previously, using a nonhuman primate model, we demonstrated that priming with fusion peptide (FP)-carrier conjugate immunogens followed by boosting with Env trimers reduced the anti-base response. Further, we demonstrated that longer immunization intervals further reduced anti-base responses and increased neutralization breadth. Here, we demonstrate that long trimer-boosting intervals, but not long FP immunization intervals, reduce the anti-base response. Additionally, we identify that FP priming before trimer immunization enhances antibody avidity to the Env trimer. We also establish that adjuvants Matrix M and Adjuplex further reduce anti-base responses and increase neutralizing titers. FP priming, long trimer-immunization interval, and an appropriate adjuvant can thus reduce anti-base antibody responses and improve Env-directed vaccine outcomes.
- Published
- 2024