The TLR-4 agonist adjuvant, GLA-SE, improves magnitude and quality of immune responses elicited by the ID93 tuberculosis vaccine: first-in-human trial
| Autor: | Rhea N. Coler, Tracey A. Day, Ruth Ellis, Franco M. Piazza, Anna Marie Beckmann, Julie Vergara, Tom Rolf, Lenette Lu, Galit Alter, David Hokey, Lakshmi Jayashankar, Robert Walker, Margaret Ann Snowden, Tom Evans, Ann Ginsberg, Steven G. Reed, The TBVPX-113 Study Team |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy Tuberculosis medicine.medical_treatment Immunology lcsh:RC254-282 Article 03 medical and health sciences 0302 clinical medicine Immune system Antigen medicine Pharmacology (medical) Adverse effect Pharmacology biology business.industry medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 3. Good health Vaccination 030104 developmental biology Infectious Diseases biology.protein Antibody Tuberculosis vaccines business lcsh:RC581-607 Adjuvant 030215 immunology |
| Zdroj: | npj Vaccines, Vol 3, Iss 1, Pp 1-9 (2018) NPJ Vaccines |
| ISSN: | 2059-0105 |
| Popis: | Tuberculosis (TB) is the leading cause of infectious death worldwide. Development of improved TB vaccines that boost or replace BCG is a major global health goal. ID93 + GLA-SE is a fusion protein TB vaccine candidate combined with the Toll-like Receptor 4 agonist adjuvant, GLA-SE. We conducted a phase 1, randomized, double-blind, dose-escalation clinical trial to evaluate two dose levels of the ID93 antigen, administered intramuscularly alone or in combination with two dose levels of the GLA-SE adjuvant, in 60 BCG-naive, QuantiFERON-negative, healthy adults in the US (ClinicalTrials.gov identifier: NCT01599897). When administered as 3 injections, 28 days apart, all dose levels of ID93 alone and ID93 + GLA-SE demonstrated an acceptable safety profile. All regimens elicited vaccine-specific humoral and cellular responses. Compared with ID93 alone, vaccination with ID93 + GLA-SE elicited higher titers of ID93-specific antibodies, a preferential increase in IgG1 and IgG3 subclasses, and a multifaceted Fc-mediated effector function response. The addition of GLA-SE also enhanced the magnitude and polyfunctional cytokine profile of CD4+ T cells. The data demonstrate an acceptable safety profile and indicate that the GLA-SE adjuvant drives a functional humoral and T-helper 1 type cellular response. Tuberculosis: novel vaccine formulation elicits strong immune responses A tuberculosis vaccine containing an immunity-potentiating agent stimulated strong immune responses in a first-in-human trial. Tuberculosis (TB) is the world’s foremost cause of infectious disease deaths, yet lacks an effective vaccine for adult humans. Rhea Coler, of the Infectious Disease Research Institute, Seattle, and a team from the United States and South Africa, tested their prophylactic on 60 healthy US adults. The vaccine consisted of ID93, a fusion of TB therapeutic target proteins, and GLA-SE—a supplement to boost immune responses. The candidate proved safe in all participants, with mild-to-moderate adverse effects, and provoked promising immune responses. The formulation was significantly more effective with GLA-SE than without. Further studies will elucidate the therapeutic benefit of this formulation and its ability to combat the pathogenicity of TB. |
| Databáze: | OpenAIRE |
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