Riddler Sharon A, Moodie Zoe, Clark Jesse, Yen Catherine, Allen Mary, Furch Briana D, Lu Huiyin, Grant Shannon, Mondal Kajari, Anderson Maija, Maenza Janine, Lemos Maria P, Woodward Davis Amanda S, Walsh Stephen R, Sobieszczyk Magdalena E, Frank Ian, Goepfert Paul, Stephenson Kathryn E, Baden Lindsey R, Tieu Hong-Van, Keefer Michael C, McElrath M Juliana, Kublin James G, Corey Lawrence
Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (S.A.R.).
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington (Z.M., B.D.F., H.L., S.G., K.M., M.Anderson, J.M., M.P.L., A.S.W.D., M.J.M., J.G.K., L.C.).
Ann Intern Med. 2025 Jul;178(7):963-974. doi: 10.7326/ANNALS-24-02701. Epub 2025 Apr 29.
The mRNA platform is under investigation for many vaccines, including HIV-1 vaccines.
To evaluate the safety and tolerability of 3 investigational HIV-1 trimer mRNA vaccines.
Safety analysis of mRNA vaccination in a phase 1, randomized, open-label trial. (ClinicalTrials.gov: NCT05217641).
Ten research sites in the United States.
108 volunteers aged 18 to 55 years without HIV-1.
Investigational HIV-1 BG505 MD39.3 trimer mRNA vaccines (gp140 soluble trimer, gp151 membrane-bound trimer, and gp151 CD4KO membrane-bound trimer) at doses of 100 and 250 mcg at 0, 2, and 6 months.
Solicited and unsolicited adverse reactions and events reported during the 12 months after the first vaccination.
Participants ( = 108) were randomly assigned to 6 vaccine groups. Mild to moderate local and systemic solicited events were common. Eighty participants reported 190 unsolicited adverse events (AEs); 30 were considered to be related to a study product. Most (73%) related AEs were mild, and the rest were moderate. Among related AEs, urticaria was reported by 7 of 108 participants (7% [95% CI, 3% to 13%]), 4 of whom had unresolved, intermittent urticaria at 12 months. In post hoc analyses, demographic characteristics, history of allergy or medication use, and COVID-19 were not associated with urticaria. In a comparison of participants with versus without urticaria, 100% (7 of 7; CI, 65% to 100%) versus 37% (37 of 101; CI, 28% to 46%) reported previous Moderna COVID-19 vaccination, 29% (2 of 7; CI, 8% to 64%) versus 76% (77 of 101; CI, 67% to 84%) reported previous Pfizer-BioNTech COVID-19 vaccination, and 0% (0 of 7; CI, 0% to 35%) versus 5% (5 of 101; CI, 2% to 11%) reported no previous mRNA COVID-19 vaccination.
Lack of a placebo group, open-label study, and post hoc evaluation of urticarial risk.
Urticarial reactions associated with experimental HIV-1 mRNA vaccines were observed in this trial. Studies to investigate the mechanism and approaches to mitigate these reactions are underway to further advance HIV-1 vaccine research.
National Institutes of Health, National Institute of Allergy and Infectious Diseases.
信使核糖核酸（mRNA）平台正在被用于多种疫苗的研究，包括人类免疫缺陷病毒1型（HIV-1）疫苗。
评估3种研究性HIV-1三聚体mRNA疫苗的安全性和耐受性。
在一项1期随机开放标签试验中对mRNA疫苗接种进行安全性分析。（ClinicalTrials.gov：NCT05217641）。
美国的10个研究地点。
108名年龄在18至55岁之间且未感染HIV-1的志愿者。
研究性HIV-1 BG505 MD39.3三聚体mRNA疫苗（gp140可溶性三聚体、gp151膜结合三聚体和gp151 CD4KO膜结合三聚体），分别在0、2和6个月时给予100微克和250微克剂量。
首次接种疫苗后12个月内报告的主动和被动不良反应及事件。
108名参与者被随机分配到6个疫苗组。轻度至中度的局部和全身主动事件很常见。80名参与者报告了190起被动不良事件（AE）；其中30起被认为与研究产品有关。大多数（73%）相关AE为轻度，其余为中度。在相关AE中，108名参与者中有7名（7%[95%CI，3%至13%]）报告出现荨麻疹，其中4人在12个月时荨麻疹未消退且呈间歇性发作。在事后分析中，人口统计学特征、过敏或用药史以及新冠病毒病（COVID-19）与荨麻疹无关。在有荨麻疹和无荨麻疹的参与者对比中，有荨麻疹者100%（7/7；CI，65%至100%）报告曾接种过莫德纳COVID-19疫苗，无荨麻疹者为37%（101/37；CI，28%至46%）；有荨麻疹者29%（2/7；CI，8%至64%）报告曾接种过辉瑞-BioNTech COVID-19疫苗，无荨麻疹者为76%（101/77；CI，67%至84%）；有荨麻疹者0%（0/7；CI，0%至35%）报告未曾接种过mRNA COVID-19疫苗，无荨麻疹者为5%（101/5；CI，2%至11%）。
缺乏安慰剂组、开放标签研究以及对荨麻疹风险的事后评估。
在本试验中观察到了与实验性HIV-1 mRNA疫苗相关的荨麻疹反应。正在开展研究以探究这些反应的机制及缓解方法，以进一步推进HIV-1疫苗研究。
美国国立卫生研究院，国家过敏和传染病研究所。
