Dose, Safety, Tolerability, and Immunogenicity of an HIV-1 Vaccine, VRC-HIVRGP096-00-VP, With Alum in Healthy Adults

Summary

Background: HIV stands for human immunodeficiency virus, which is the virus that causes AIDS. There is currently no licensed vaccine to prevent HIV infection. Researchers want to test a vaccine called Trimer 4571 for the first time. It was made at the National Institutes of Health (NIH) and contains no HIV. The vaccine is mixed with a substance called alum and injected in the arm. Alum is included to boost the body's immune response to the vaccine. It has been used in licensed vaccines for over 60 years and has been found to be safe. Objectives: To see if the vaccine Trimer 4571 is safe, well-tolerated, and to study immune responses to it. Eligibility: Healthy adults ages 18-50 years Design: Participants were screened with a physical exam and blood tests. They agreed to not become pregnant and to avoid behavior that would put them at high-risk for HIV infection during the study. Participants had about 15 study visits over about 9 months. The first 6 participants received a low dose of the vaccine mixed with alum. Once the low dose was deemed safe, 10 new participants were allocated to receive a higher dose. All participants were randomly assigned to get the vaccine by injection in a muscle or under the skin. All participants received a total of 3 vaccine injections over 20 weeks. Each visit where participants received the vaccine lasted about 5 hours. Participants were watched after each injection. Participants who were able to get pregnant would have a pregnancy test before each injection. Participants received a thermometer and recorded their temperature and symptoms every day for 1 week after each injection. The injection site was checked for redness, swelling, or bruising. At follow-up visits, participants had blood drawn and checked for health changes or problems. Follow up visits lasted about 1-2 hours.

Timeline

Start

2019-03-07

Primary completion

2020-06-24

Completion

2020-06-24

Publications

• Background Sanders RW, Derking R, Cupo A, Julien JP, Yasmeen A, de Val N, Kim HJ, Blattner C, de la Pena AT, Korzun J, Golabek M, de Los Reyes K, Ketas TJ, van Gils MJ, King CR, Wilson IA, Ward AB, Klasse PJ, Moore JP. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies. PLoS Pathog. 2013 Sep;9(9):e1003618. doi: 10.1371/journal.ppat.1003618. Epub 2013 Sep 19.
• Background Kwon YD, Pancera M, Acharya P, Georgiev IS, Crooks ET, Gorman J, Joyce MG, Guttman M, Ma X, Narpala S, Soto C, Terry DS, Yang Y, Zhou T, Ahlsen G, Bailer RT, Chambers M, Chuang GY, Doria-Rose NA, Druz A, Hallen MA, Harned A, Kirys T, Louder MK, O'Dell S, Ofek G, Osawa K, Prabhakaran M, Sastry M, Stewart-Jones GB, Stuckey J, Thomas PV, Tittley T, Williams C, Zhang B, Zhao H, Zhou Z, Donald BR, Lee LK, Zolla-Pazner S, Baxa U, Schon A, Freire E, Shapiro L, Lee KK, Arthos J, Munro JB, Blanchard SC, Mothes W, Binley JM, McDermott AB, Mascola JR, Kwong PD. Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env. Nat Struct Mol Biol. 2015 Jul;22(7):522-31. doi: 10.1038/nsmb.3051. Epub 2015 Jun 22.
• Background Chuang GY, Geng H, Pancera M, Xu K, Cheng C, Acharya P, Chambers M, Druz A, Tsybovsky Y, Wanninger TG, Yang Y, Doria-Rose NA, Georgiev IS, Gorman J, Joyce MG, O'Dell S, Zhou T, McDermott AB, Mascola JR, Kwong PD. Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity. J Virol. 2017 Apr 28;91(10):e02268-16. doi: 10.1128/JVI.02268-16. Print 2017 May 15.
• Background U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS. Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1. [July 2017]. Available from: https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf
• Houser KV, Gaudinski MR, Happe M, Narpala S, Verardi R, Sarfo EK, Corrigan AR, Wu R, Rothwell RS, Novik L, Hendel CS, Gordon IJ, Berkowitz NM, Cartagena CT, Widge AT, Coates EE, Strom L, Hickman S, Conan-Cibotti M, Vazquez S, Trofymenko O, Plummer S, Stein J, Case CL, Nason M, Biju A, Parchment DK, Changela A, Cheng C, Duan H, Geng H, Teng IT, Zhou T, O'Connell S, Barry C, Carlton K, Gall JG, Flach B, Doria-Rose NA, Graham BS, Koup RA, McDermott AB, Mascola JR, Kwong PD, Ledgerwood JE; VRC 018 Study Team. 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. EClinicalMedicine. 2022 Jun 1;48:101477. doi: 10.1016/j.eclinm.2022.101477. eCollection 2022 Jun.

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