Safety and immunogenicity of an HIV-1 prefusion-stabilized envelope trimer (Trimer 4571) vaccine in healthy adults: A first-in-human open-label, randomized, dose-escalation, phase 1 clinical trial

作者：Katherine V. Houser, Martin R. Gaudinski, Myra Happe, Sandeep Narpala, Raffaello Verardi, Edward K. Sarfo, Angela R. Corrigan, Richard Wu, Ro Shauna Rothwell, Laura Novik, Cynthia S. Hendel, Ingelise J. Gordon, Nina M. Berkowitz, Cora Trelles Cartagena, Alicia T. Widge, Emily E. Coates, Larisa Strom, Somia P. Hickman, Michelle Conan-Cibotti, Sandra Vazquez, Olga Trofymenko, Sarah A. Plummer, Judy Stein, Christopher L. Case, Martha Nason, Andrea Biju, Danealle K. Parchment, Anita Changela, Cheng Cheng, Hongying Duan, Hui Geng, I‐Ting Teng, Tongqing Zhou, Sarah O’Connell, Chris Barry, Kevin Carlton, Jason G. Gall, Britta Flach, Nicole A. Doria‐Rose, Barney S. Graham, Richard A. Koup, Adrian B. McDermott, John R. Mascola, Peter D. Kwong, Julie E. Ledgerwood · 发表于：EClinicalMedicine · 年份：2022 · DOI：10.1016/j.eclinm.2022.101477 · 被引用次数：44 · 研究领域：Intramuscular injections and effects、HIV Research and Treatment、Immunotherapy and Immune Responses

Background: Advances in therapeutic drugs have increased life-expectancies for HIV-infected individuals, but the need for an effective vaccine remains. We assessed safety and immunogenicity of HIV-1 vaccine, Trimer 4571 (BG505 DS-SOSIP.664) adjuvanted with aluminum hydroxide (alum), in HIV-negative adults. Methods: We conducted a phase I, randomized, open-label, dose-escalation trial at the National Institutes of Health Clinical Center in Bethesda, MD, USA. Eligible participants were HIV-negative, healthy adults between 18-50 years. Participants were randomized 1:1 to receive Trimer 4571 adjuvanted with 500 mcg alum by either the subcutaneous (SC) or intramuscular (IM) route at weeks 0, 8, and 20 in escalating doses of 100 mcg or 500 mcg. The primary objectives were to evaluate the safety and tolerability of Trimer 4571 with a secondary objective of evaluating vaccine-induced antibody responses. The primary and safety endpoints were evaluated in all participants who received at least one dose of Trimer 4571. Trial results were summarized using descriptive statistics. This trial is registered at ClinicalTrials.gov, NCT03783130. Findings: Between March 7 and September 11, 2019, 16 HIV-negative participants were enrolled, including six (38%) males and ten (62%) females. All participants received three doses of Trimer 4571. Solicited reactogenicity was mild to moderate in severity, with one isolated instance of severe injection site redness (6%) following a third 500 mcg SC admin...