Ramezani-Rad Parham, Marina-Zárate Ester, Maiorino Laura, Myers Amber, Kaczmarek Michaels Katarzyna, Pires Ivan S, Bloom Nathaniel I, Melo Mariane B, Lemnios Ashley A, Lopez Paul G, Cottrell Christopher A, Burton Iszac, Groschel Bettina, Pradhan Arpan, Stiegler Gabriela, Budai Magdolna, Kumar Daniel, Pallerla Sam, Sayeed Eddy, Sagar Sangeetha L, Kasturi Sudhir Pai, Van Rompay Koen Ka, Hangartner Lars, Wagner Andreas, Burton Dennis R, Schief William R, Crotty Shane, Irvine Darrell J
Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.
Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, California, USA.
J Clin Invest. 2025 Mar 4;135(8). doi: 10.1172/JCI185292. eCollection 2025 Apr 15.
Induction of durable protective immune responses is the main goal of prophylactic vaccines, and adjuvants play a role as drivers of such responses. Despite advances in vaccine strategies, development of a safe and effective HIV vaccine remains a significant challenge. Use of an appropriate adjuvant is crucial to the success of HIV vaccines. Here we assessed the saponin/MPLA nanoparticle (SMNP) adjuvant with an HIV envelope (Env) trimer, evaluating the safety and effect of multiple variables - including adjuvant dose (16-fold dose range), immunization route, and adjuvant composition - on the establishment of Env-specific memory T and B cell (TMem and BMem) responses and long-lived plasma cells in nonhuman primates (NHPs). Robust BMem were detected in all groups, but a 6-fold increase was observed in the highest- versus the lowest-SMNP-dose group. Similarly, stronger vaccine responses were induced by the highest SMNP dose in CD40L+OX40+ CD4+ TMem (11-fold), IFN-γ+ CD4+ TMem (15-fold), IL21+ CD4+ TMem (9-fold), circulating T follicular helper cells (TFH; 3.6-fold), BM plasma cells (7-fold), and binding IgG (1.3-fold). Substantial tier 2 neutralizing antibodies were only observed in the higher-SMNP-dose groups. These investigations highlight the dose-dependent potency of SMNP and its relevance for human use and next-generation vaccines.
诱导持久的保护性免疫反应是预防性疫苗的主要目标，佐剂作为此类反应的驱动因素发挥作用。尽管疫苗策略取得了进展，但开发安全有效的HIV疫苗仍然是一项重大挑战。使用合适的佐剂对HIV疫苗的成功至关重要。在此，我们评估了与HIV包膜（Env）三聚体联合使用的皂苷/MPLA纳米颗粒（SMNP）佐剂，评估了多个变量——包括佐剂剂量（16倍剂量范围）、免疫途径和佐剂组成——对非人灵长类动物（NHPs）中Env特异性记忆T细胞和B细胞（TMem和BMem）反应以及长寿浆细胞建立的安全性和效果。在所有组中均检测到强大的BMem，但在最高SMNP剂量组与最低SMNP剂量组之间观察到6倍的增加。同样，最高SMNP剂量在CD40L+OX40+ CD4+ TMem（11倍）、IFN-γ+ CD4+ TMem（15倍）、IL21+ CD4+ TMem（9倍）、循环滤泡辅助性T细胞（TFH；3.6倍）、骨髓浆细胞（7倍）和结合IgG（1.3倍）中诱导出更强的疫苗反应。仅在较高SMNP剂量组中观察到大量的2级中和抗体。这些研究突出了SMNP的剂量依赖性效力及其对人类使用和下一代疫苗的相关性。
