دورية أكاديمية
أعرض في EDS

Trivalent mosaic or consensus HIV immunogens prime humoral and broader cellular immune responses in adults.

التفاصيل البيبلوغرافية
العنوان: Trivalent mosaic or consensus HIV immunogens prime humoral and broader cellular immune responses in adults.
المؤلفون: Cohen KW; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Fiore-Gartland A; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Walsh SR; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA., Yusim K; Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, and New Mexico Consortium, Los Alamos, New Mexico, USA., Frahm N; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.; Department of Global Health, University of Washington, Seattle, Washington, USA., Elizaga ML; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Maenza J; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Scott H; San Francisco Department of Public Health, San Francisco, California, USA., Mayer KH; Harvard Medical School, Boston, Massachusetts, USA.; The Fenway Institute, Fenway Health, Boston, Massachusetts, USA., Goepfert PA; University of Alabama at Birmingham, Birmingham, Alabama, USA., Edupuganti S; Emory University, Atlanta, Georgia, USA., Pantaleo G; Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland., Hutter J; Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA., Morris DE; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., De Rosa SC; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Geraghty DE; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Robb ML; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA., Michael NL; Walter Reed Army Institute of Research, Silver Spring, Maryland, USA., Fischer W; Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, and New Mexico Consortium, Los Alamos, New Mexico, USA., Giorgi EE; Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, and New Mexico Consortium, Los Alamos, New Mexico, USA., Malhi H; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Pensiero MN; Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA., Ferrari G; Duke Human Vaccine Institute and.; Department of Surgery, Duke University, Durham, North Carolina, USA., Tomaras GD; Duke Human Vaccine Institute and.; Department of Surgery, Duke University, Durham, North Carolina, USA., Montefiori DC; Duke Human Vaccine Institute and.; Department of Surgery, Duke University, Durham, North Carolina, USA., Gilbert PB; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., McElrath MJ; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA., Haynes BF; Duke Human Vaccine Institute and., Korber BT; Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, and New Mexico Consortium, Los Alamos, New Mexico, USA., Baden LR; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.; Harvard Medical School, Boston, Massachusetts, USA.
مؤلفون مشاركون: NIAID HVTN 106 Study Group
المصدر: The Journal of clinical investigation [J Clin Invest] 2023 Feb 15; Vol. 133 (4). Date of Electronic Publication: 2023 Feb 15.
نوع المنشور: Randomized Controlled Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Electronic Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
أسماء مطبوعة: Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
Original Publication: New Haven [etc.] American Society for Clinical Investigation.
مواضيع طبية MeSH: HIV Infections* , AIDS Vaccines* , Vaccines, DNA*, Animals ; Consensus ; Immunity, Cellular ; Vaccination ; Vaccinia virus ; HIV Antibodies
مستخلص: BACKGROUNDMosaic and consensus HIV-1 immunogens provide two distinct approaches to elicit greater breadth of coverage against globally circulating HIV-1 and have shown improved immunologic breadth in nonhuman primate models.METHODSThis double-blind randomized trial enrolled 105 healthy HIV-uninfected adults who received 3 doses of either a trivalent global mosaic, a group M consensus (CON-S), or a natural clade B (Nat-B) gp160 env DNA vaccine followed by 2 doses of a heterologous modified vaccinia Ankara-vectored HIV-1 vaccine or placebo. We performed prespecified blinded immunogenicity analyses at day 70 and day 238 after the first immunization. T cell responses to vaccine antigens and 5 heterologous Env variants were fully mapped.RESULTSEnv-specific CD4+ T cell responses were induced in 71% of the mosaic vaccine recipients versus 48% of the CON-S recipients and 48% of the natural Env recipients. The mean number of T cell epitopes recognized was 2.5 (95% CI, 1.2-4.2) for mosaic recipients, 1.6 (95% CI, 0.82-2.6) for CON-S recipients, and 1.1 (95% CI, 0.62-1.71) for Nat-B recipients. Mean breadth was significantly greater in the mosaic group than in the Nat-B group using overall (P = 0.014), prime-matched (P = 0.002), heterologous (P = 0.046), and boost-matched (P = 0.009) measures. Overall T cell breadth was largely due to Env-specific CD4+ T cell responses.CONCLUSIONPriming with a mosaic antigen significantly increased the number of epitopes recognized by Env-specific T cells and enabled more, albeit still limited, cross-recognition of heterologous variants. Mosaic and consensus immunogens are promising approaches to address global diversity of HIV-1.TRIAL REGISTRATIONClinicalTrials.gov NCT02296541.FUNDINGUS NIH grants UM1 AI068614, UM1 AI068635, UM1 AI068618, UM1 AI069412, UL1 RR025758, P30 AI064518, UM1 AI100645, and UM1 AI144371, and Bill & Melinda Gates Foundation grant OPP52282.
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معلومات مُعتمدة: UM1 AI100645 United States AI NIAID NIH HHS; R37 AI150590 United States AI NIAID NIH HHS; UM1 AI069412 United States AI NIAID NIH HHS; UM1 AI069481 United States AI NIAID NIH HHS; UM1 AI068614 United States AI NIAID NIH HHS; UM1 AI068618 United States AI NIAID NIH HHS; UM1 AI068635 United States AI NIAID NIH HHS; UL1 RR025758 United States RR NCRR NIH HHS; P30 AI064518 United States AI NIAID NIH HHS; UM1 AI144371 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: AIDS vaccine; AIDS/HIV; Cellular immune response; Vaccines
سلسلة جزيئية: ClinicalTrials.gov NCT02296541
المشرفين على المادة: 0 (AIDS Vaccines)
0 (HIV Antibodies)
0 (Vaccines, DNA)
تواريخ الأحداث: Date Created: 20230214 Date Completed: 20230216 Latest Revision: 20230919
رمز التحديث: 20230919
مُعرف محوري في PubMed: PMC9927951
DOI: 10.1172/JCI163338
PMID: 36787249
قاعدة البيانات: MEDLINE
الوصف
تدمد:1558-8238
DOI:10.1172/JCI163338