Sharon A Riddler, Zoe Moodie, Jesse Clark, Catherine Yen, Mary Allen, Briana D Furch, Huiyin Lu, Shannon Grant, Kajari Mondal, Maija Anderson, Janine Maenza, Maria P Lemos, Amanda S Woodward Davis, Stephen R Walsh, Magdalena E Sobieszczyk, Ian Frank, Paul Goepfert, Kathryn E Stephenson, Lindsey R Baden, Hong-Van Tieu, Michael C Keefer, M Juliana McElrath, James G Kublin, Lawrence Corey
{"title":"在一项1期、随机、开放标签临床试验（HVTN 302）中，HIV-1 BG505 MD39.3三聚体mRNA疫苗接种后慢性荨麻疹的高频率","authors":"Sharon A Riddler, Zoe Moodie, Jesse Clark, Catherine Yen, Mary Allen, Briana D Furch, Huiyin Lu, Shannon Grant, Kajari Mondal, Maija Anderson, Janine Maenza, Maria P Lemos, Amanda S Woodward Davis, Stephen R Walsh, Magdalena E Sobieszczyk, Ian Frank, Paul Goepfert, Kathryn E Stephenson, Lindsey R Baden, Hong-Van Tieu, Michael C Keefer, M Juliana McElrath, James G Kublin, Lawrence Corey","doi":"10.7326/ANNALS-24-02701","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The mRNA platform is under investigation for many vaccines, including HIV-1 vaccines.</p><p><strong>Objective: </strong>To evaluate the safety and tolerability of 3 investigational HIV-1 trimer mRNA vaccines.</p><p><strong>Design: </strong>Safety analysis of mRNA vaccination in a phase 1, randomized, open-label trial. (ClinicalTrials.gov: NCT05217641).</p><p><strong>Setting: </strong>Ten research sites in the United States.</p><p><strong>Participants: </strong>108 volunteers aged 18 to 55 years without HIV-1.</p><p><strong>Intervention: </strong>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.</p><p><strong>Measurements: </strong>Solicited and unsolicited adverse reactions and events reported during the 12 months after the first vaccination.</p><p><strong>Results: </strong>Participants (<i>n</i> = 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.</p><p><strong>Limitations: </strong>Lack of a placebo group, open-label study, and post hoc evaluation of urticarial risk.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Primary funding source: </strong>National Institutes of Health, National Institute of Allergy and Infectious Diseases.</p>","PeriodicalId":7932,"journal":{"name":"Annals of Internal Medicine","volume":" ","pages":"963-974"},"PeriodicalIF":19.6000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"High Frequency of Chronic Urticaria Following an Investigational HIV-1 BG505 MD39.3 Trimer mRNA Vaccine in a Phase 1, Randomized, Open-Label Clinical Trial (HVTN 302).\",\"authors\":\"Sharon A Riddler, Zoe Moodie, Jesse Clark, Catherine Yen, Mary Allen, Briana D Furch, Huiyin Lu, Shannon Grant, Kajari Mondal, Maija Anderson, Janine Maenza, Maria P Lemos, Amanda S Woodward Davis, Stephen R Walsh, Magdalena E Sobieszczyk, Ian Frank, Paul Goepfert, Kathryn E Stephenson, Lindsey R Baden, Hong-Van Tieu, Michael C Keefer, M Juliana McElrath, James G Kublin, Lawrence Corey\",\"doi\":\"10.7326/ANNALS-24-02701\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The mRNA platform is under investigation for many vaccines, including HIV-1 vaccines.</p><p><strong>Objective: </strong>To evaluate the safety and tolerability of 3 investigational HIV-1 trimer mRNA vaccines.</p><p><strong>Design: </strong>Safety analysis of mRNA vaccination in a phase 1, randomized, open-label trial. (ClinicalTrials.gov: NCT05217641).</p><p><strong>Setting: </strong>Ten research sites in the United States.</p><p><strong>Participants: </strong>108 volunteers aged 18 to 55 years without HIV-1.</p><p><strong>Intervention: </strong>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.</p><p><strong>Measurements: </strong>Solicited and unsolicited adverse reactions and events reported during the 12 months after the first vaccination.</p><p><strong>Results: </strong>Participants (<i>n</i> = 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.</p><p><strong>Limitations: </strong>Lack of a placebo group, open-label study, and post hoc evaluation of urticarial risk.</p><p><strong>Conclusion: </strong>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.</p><p><strong>Primary funding source: </strong>National Institutes of Health, National Institute of Allergy and Infectious Diseases.</p>\",\"PeriodicalId\":7932,\"journal\":{\"name\":\"Annals of Internal Medicine\",\"volume\":\" \",\"pages\":\"963-974\"},\"PeriodicalIF\":19.6000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Internal Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.7326/ANNALS-24-02701\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/4/29 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Internal Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7326/ANNALS-24-02701","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/29 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
High Frequency of Chronic Urticaria Following an Investigational HIV-1 BG505 MD39.3 Trimer mRNA Vaccine in a Phase 1, Randomized, Open-Label Clinical Trial (HVTN 302).
Background: The mRNA platform is under investigation for many vaccines, including HIV-1 vaccines.
Objective: To evaluate the safety and tolerability of 3 investigational HIV-1 trimer mRNA vaccines.
Design: Safety analysis of mRNA vaccination in a phase 1, randomized, open-label trial. (ClinicalTrials.gov: NCT05217641).
Setting: Ten research sites in the United States.
Participants: 108 volunteers aged 18 to 55 years without HIV-1.
Intervention: 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.
Measurements: Solicited and unsolicited adverse reactions and events reported during the 12 months after the first vaccination.
Results: Participants (n = 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.
Limitations: Lack of a placebo group, open-label study, and post hoc evaluation of urticarial risk.
Conclusion: 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.
Primary funding source: National Institutes of Health, National Institute of Allergy and Infectious Diseases.
期刊介绍：
Established in 1927 by the American College of Physicians (ACP), Annals of Internal Medicine is the premier internal medicine journal. Annals of Internal Medicine’s mission is to promote excellence in medicine, enable physicians and other health care professionals to be well informed members of the medical community and society, advance standards in the conduct and reporting of medical research, and contribute to improving the health of people worldwide. To achieve this mission, the journal publishes a wide variety of original research, review articles, practice guidelines, and commentary relevant to clinical practice, health care delivery, public health, health care policy, medical education, ethics, and research methodology. In addition, the journal publishes personal narratives that convey the feeling and the art of medicine.
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