2025年5月15日出版的《科学》杂志发表了美国斯克里普斯研究所
在美国的IAVI-G002和卢旺达和南非的IAVI-G003两项随机、开放标签的1期人体临床试验中，课题组评估了mRNA编码纳米颗粒作为启动免疫原（两项试验）和首次增强免疫原（IAVI-G002）的安全性和免疫原性。除了18%的IAVI-G002参与者出现皮肤反应外，疫苗总体上是安全且耐受性良好的。引物诱导的bnAb前体具有大量的频率和SHM，而异源异构体促进诱导的SHM、亲和力和中和活性增加，对bnAb的发展有促进作用。研究结果证实了异源异体增强可以促进bnAb前体成熟的概念，并证明了bnAb在艾滋病毒负担最高的非洲启动。
研究人员表示，一种领先的HIV疫苗策略需要启动免疫原来诱导广泛中和抗体（bnAb）前体，然后是一系列异源性抗体增强剂来诱导体细胞超突变（SHM）并产生bnAb。
附：英文原文
Title: Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans
Author: Jordan R. Willis, Madhu Prabhakaran, Michelle Muthui, Ansuya Naidoo, Troy Sincomb, Weiwei Wu, Christopher A. Cottrell, Elise Landais, Allan C. deCamp, Nahid R. Keshavarzi, Oleksandr Kalyuzhniy, Jeong Hyun Lee, Linda M. Murungi, Wilfrida A Ogonda, Nicole L. Yates, Martin M. Corcoran, Swastik Phulera, Joel Musando, Amanda Tsai, Gabrielle Lemire, Yiakon Sein, Michael Muteti, Praveen Alamuri, Jennifer A. Bohl, Drienna Holman, Sunny Himansu, Brett Leav, Caroline Reuter, Li-An Lin, Baoyu Ding, Chunla He, Walter L. Straus, Kellie J. MacPhee, Isabel Regadas, Diana V. Nyabundi, Ruth Chirchir, Aggrey Anzala, John N. Kimotho, Caleb Kibet, Kelli Greene, Hongmei Gao, Erica Beatman, Kiara Benson, Dominick Laddy, David M. Brown, Rhianna Bronson, Jalen Baptiste, Suprabhath Gajjala, Zahra Rikhtegaran-Tehrani, Alison Benner, Mukundhan Ramaswami, Danny Lu, Nushin Alavi, Sonya Amirzehni, Michael Kubitz, Ryan Tingle, Erik Georgeson, Nicole Phelps, Yumiko Adachi, Alessia Liguori, Claudia Flynn, Katherine McKenney, Xiaoya Zhou, D. Collins Owuor, Sharon Owuor, Soo-Young Kim, Michael Duff, Ju Yeong Kim, Grace Gibson, Sabyasachi Baboo, Jolene Diedrich, Torben Schiffner, Marisa Shields, Mabela Matsoso, Jennifer Santos, Kristen Syvertsen, Allison Kennedy, Melissa Schroeter, Johan Vekemans, John Yates, James C. Paulson, Ollivier Hyrien, Adrian B. McDermott, Pholo Maenetje, Julien Nyombayire, Etienne Karita, Rosine Ingabire, Vinodh Edward, Vincent Muturi-Kioi, Janine Maenza, Adrienne E. Shapiro, M. Juliana McElrath, Srilatha Edupuganti, Barbara S. Taylor, David Diemert, Gabriel Ozorowski, Richard A. Koup, David Montefiori, Andrew B. Ward, Gunilla Karlsson Hedestam, Georgia Tomaras, Devin J. Hunt, Daniel Muema, Devin Sok, Dagna S. Laufer, Sarah F. Andrews, Eunice W. Nduati, William R. Schief
Issue&Volume: 2025-05-15
Abstract: A leading HIV vaccine strategy requires a priming immunogen to induce broadly neutralizing antibody (bnAb) precursors, followed by a series of heterologous boosters to elicit somatic hypermutation (SHM) and produce bnAbs. In two randomized, open-label phase 1 human clinical trials, IAVI-G002 in the United States and IAVI-G003 in Rwanda and South Africa, we evaluated the safety and immunogenicity of mRNA-encoded nanoparticles as priming immunogens (both trials) and first-boosting immunogens (IAVI-G002). The vaccines were generally safe and well tolerated, except 18% of IAVI-G002 participants experienced skin reactions. Priming induced bnAb precursors with substantial frequencies and SHM, and heterologous boosting elicited increased SHM, affinity, and neutralization activity toward bnAb development. The results establish clinical proof of concept that heterologous boosting can advance bnAb-precursor maturation and demonstrate bnAb priming in Africa where the HIV burden is highest.
DOI: adr8382
Source: https://www.science.org/doi/10.1126/science.adr8382