作者: Grunenberg, Nicole ; Jones, Megan ; Jensen, Ryan L. ; Ferrari, Guido ; Gray, Glenda E ; Dintwe, One ; Hosseinipour, Mina C ; Van Der Meeren, Olivier ; Robinson, Samuel T ; Kublin, James G. ; Tomaras, Georgia D ; Monaco, Cynthia L. ; Kublin, James G ; Koutsoukos, Marguerite ; Andersen-Nissen, Erica ; Jensen, Ryan L ; Seaton, Kelly E. ; Huang, Yunda ; Gilbert, Peter B. ; Hosseinipour, Mina C. ; Mann, Philipp ; deCamp, Allan ; McElrath, M Juliana ; Monaco, Cynthia L ; Lu, Huiyin ; Church, E Chandler ; Heptinstall, Jack ; Tomaras, Georgia D. ; Church, E. Chandler ; McElrath, M. Juliana ; Ding, Song ; Gilbert, Peter B ; Hutter, Julia ; Garrett, Nigel ; Gray, Glenda E. ; Seaton, Kelly E ; Robinson, Samuel T. ; Corey, Lawrence ; Pantaleo, Giuseppe

Background:An effective vaccine is required to end the HIV pandemic. We evaluated the safety and immunogenicity of a DNA (DNA-HIV-PT123) vaccine with low- or high-dose bivalent (TV1.C and 1086.C glycoprotein 120) subtype C envelope protein combinations, adjuvanted with MF59 or AS01B.Methods:HIV Vaccine Trials Network (HVTN)108 was a randomized, placebo-controlled, double-blind, phase 1/2a trial conducted in the United States and South Africa. HIV-negative adults were randomly assigned to 1 of 7 intervention arms or placebo to assess DNA prime with DNA/protein/adjuvant boosts, DNA/protein/adjuvant co-administration, and low-dose protein/adjuvant regimens. HVTN111 trial participants who received an identical regimen were also included. Outcomes included safety and immunogenicity 2 weeks and 6 months after final vaccination.Results:From June 2016 to July 2018, 400 participants were enrolled (N = 334 HVTN108, N = 66 HVTN111); 370 received vaccine and 30 received placebo. There were 48 grade 3 and 3 grade 4 reactogenicity events among 39/400 (9.8%) participants, and 32 mild/moderate-related adverse events in 23/400 (5.8%) participants. All intervention groups demonstrated high IgG response rates (>89%) and high magnitudes to HIV-1 Env gp120 and gp140 proteins; response rates for AS01B-adjuvanted groups approached 100%. V1V2 IgG magnitude, Fc-mediated functions, IgG3 Env response rates, and CD4+ T-cell response magnitudes and rates were higher in the AS01B-adjuvanted groups. The AS01B-adjuvanted low-dose protein elicited greater IgG responses than the higher protein dose.Conclusions:The vaccine regimens were generally well tolerated. Co-administration of DNA with AS01B-adjuvanted bivalent Env gp120 elicited the strongest humoral responses; AS01B-adjuvanted regimens elicited stronger CD4+ T-cell responses, justifying further evaluation.ClinicalTrials.gov registration: NCT02915016, registered 26 September 2016.

2023-10-06·Viruses

Higher HIV-1 Env gp120-Specific Antibody-Dependent Cellular Cytotoxicity (ADCC) Activity Is Associated with Lower Levels of Defective HIV-1 Provirus.

Article

作者: Richardson, Barbra A ; Wamalwa, Dalton ; Yucha, Ryan ; Lehman, Dara A ; Litchford, Morgan L ; Maleche-Obimbo, Elizabeth ; Yaffe, Zak A ; Fish, Carolyn S ; John-Stewart, Grace ; Overbaugh, Julie

A cure for HIV-1 (HIV) remains unrealized due to a reservoir of latently infected cells that persist during antiretroviral therapy (ART), with reservoir size associated with adverse health outcomes and inversely with time to viral rebound upon ART cessation. Once established during ART, the HIV reservoir decays minimally over time; thus, understanding factors that impact the size of the HIV reservoir near its establishment is key to improving the health of people living with HIV and for the development of novel cure strategies. Yet, to date, few correlates of HIV reservoir size have been identified, particularly in pediatric populations. Here, we employed a cross-subtype intact proviral DNA assay (CS-IPDA) to quantify HIV provirus between one- and two-years post-ART initiation in a cohort of Kenyan children (n = 72), which had a median of 99 intact (range: 0-2469), 1340 defective (range: 172-3.84 × 10⁴), and 1729 total (range: 178-5.11 × 10⁴) HIV proviral copies per one million T cells. Additionally, pre-ART plasma was tested for HIV Env-specific antibody-dependent cellular cytotoxicity (ADCC) activity. We found that pre-ART gp120-specific ADCC activity inversely correlated with defective provirus levels (n = 68, r = -0.285, p = 0.0214) but not the intact reservoir (n = 68, r = -0.0321, p-value = 0.800). Pre-ART gp41-specific ADCC did not significantly correlate with either proviral population (n = 68; intact: r = -0.0512, p-value = 0.686; defective: r = -0.109, p-value = 0.389). This suggests specific host immune factors prior to ART initiation can impact proviruses that persist during ART.

2020-02-15·The Journal of Immunology2区 · 医学

Chemokine-Adjuvanted Plasmid DNA Induces Homing of Antigen-Specific and Non–Antigen-Specific B and T Cells to the Intestinal and Genital Mucosae

2区 · 医学

Article

作者: Kratochvil, Sven ; Shattock, Robin J. ; Aldon, Yoann ; McKay, Paul F.

AbstractPlasmid DNA is a promising vaccine platform that together with electroporation can elicit significant systemic Ab responses; however, immunity at mucosal sites remains low. In this study, we sought to program T and B cells to home to the gastrointestinal and vaginal mucosae using genetic chemokine adjuvants and assessed their impact on immune homeostasis in various distinct immune compartments. BALB/c mice were immunized i.m. with plasmid DNA encoding a model Ag HIV-1 Env gp140 and selected chemokines/cytokine and boosted intravaginally with gp140 recombinant protein. Isolated splenocytes, intestinal lymphocytes, and genital lymphocytes as well as serum and intestinal luminal contents were assessed for Ag-specific reactivity. In addition, flow cytometric analysis was performed to determine the impact on immune homeostasis at these sites. Different molecular chemokine/cytokine adjuvants effected significant alterations to the recruitment of B and T cells to the spleen, vaginal and intestinal mucosae, for example CCL25 enhanced splenic and vaginal Ag-specific T cell responses whereas CCL28 increased the levels of specific T cells only in the vaginal mucosa. The levels of Ab could be modulated in the systemic circulation, as well as the vaginal vault and intestinal lumen, with CCL20 playing a central role. Our data demonstrate that the CCL20, CCL25, and CCL28 genetic chemokine adjuvants enhance the vaccine Ag-specific humoral and cellular responses and induce homing to the intestinal and female genital mucosae.

项与 Targeting HIV-1 Env gp140 antibodies(National Institute of Allergy & Infectious Diseases) 相关的新闻（医药）

2021-06-04

·GlobeNewswire

Glycotope Poster Presentation at the 2021 American Society

Glycotope Poster Presentation at the 2021 American Society of Clinical Oncology (ASCO) Virtual Annual Meeting Berlin, Germany, June 4, 2021 - Glycotope GmbH, a biotechnology company developing antibodies against proteins carrying tumor-specific carbohydrate structures, today announced it is presenting two posters at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, which is being held virtually this year due to COVID-19. Henner Kollenberg, Managing Director of Glycotope GmbH commented: “The data presented at ASCO highlight our ability to draw on our long-standing expertise in glyco-biology to generate novel biopharmaceuticals targeting cancer indications. The data showed that a Glycotope-developed anti-TA-MUC1 antibody combined with the anti-EGFR Tomuzotuximab or Panitumumab in patients with refractory solid tumors is safe and feasible and exhibited interesting anti-tumour activity.” Poster details are as follows: Poster 2524Title: Safety and tolerability results of the GATTO study, a phase Ib study combining the anti-TA-MUC1 antibody Gatipotuzumab with the anti-EGFR Tomuzotuximab or Panitumumab in patients with refractory solid tumorsSession: Poster Session: Developmental Therapeutics—ImmunotherapyAbstract ID: 332635 Download: Poster 2522Title: Activity results of the GATTO study, a phase Ib study combining the anti-TA-MUC1 antibody Gatipotuzumab with the anti-EGFR Tomuzotuximab or Panitumumab in patients with refractory solid tumorsSession: Poster Session: Developmental Therapeutics—ImmunotherapyAbstract ID: 329709 Download: Contact Information: About GATTO The multicenter, open label phase Ib GATTO study explored the feasibility, tolerability and preliminary activity of combining Gatipotuzumab, a novel humanized monoclonal antibody binding to a tumor-associated epitope of mucin-1 (TA-MUC1) and an anti-EGFR antibody. Based on compelling preclinical evidence suggesting a complex interaction between EGFR and TA-MUC1 expressed on the tumor cell surface in driving carcinogenesis, this study assessed the tolerability, safety and preliminary activity of targeting EGFR and TA-MUC1. In this study, 50 patients with refractory solid tumors were treated with both antibodies in 5 centers in Germany, Italy and Spain. The results analysis demonstrated that combination of TA-MUC1 and EGFR targeting antibodies is safe and feasible. Encouraging anti-tumor activity was observed in heavily pretreated NSCLC and CRC patients, particularly when the commercial anti-EGFR Panitumumab was used in combination with Gatipotuzumab. Levels of soluble TA-MUC1 may have predictive value and potentially be a companion biomarker for further development of the combination. About Glycotope Glycotope is a biotechnology company utilizing a proprietary technology platform to develop uniquely tumor-specific monoclonal antibodies. Our antibodies target specific tumor-associated carbohydrate structures or protein/carbohydrate combined glyco-epitopes (GlycoTargets). Glycotope has to date discovered in excess of 150 GlycoTargets with antibodies against several of these targets currently under development.Based on their superior tumor-specificity, our antibodies are suitable for development in an array of different modes of action including naked antibodies, bispecifics, antibody-drug-conjugates, cellular therapies or fusion-proteins. Currently six clinical and pre-clinical programs based on the TA-MUC1 GlycoTarget are under development by Glycotope or its licensing partners. Visit .

小分子药物抗体免疫疗法ASCO会议

100 项与 Targeting HIV-1 Env gp140 antibodies(National Institute of Allergy & Infectious Diseases) 相关的药物交易

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