Randomized, Blinded, Dose-Ranging Trial of an Ebola Virus Glycoprotein Nanoparticle Vaccine With Matrix-M Adjuvant in Healthy Adults
| Autor: | Sarah Katharina Fehling, Louis Fries, Jay W. Hooper, Stephan Becker, Judy Wen, Verena Krähling, Gale Smith, Gregory M. Glenn, David Flyer, Thomas Strecker, Sapeckshita Agrawal, Amy Fix, Steven A. Kwilas, Nigel Thomas, Maggie Lewis, Iksung Cho |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_treatment Antibodies Viral medicine.disease_cause Immunoglobulin G Young Adult 03 medical and health sciences 0302 clinical medicine Immune system Pseudovirion Adjuvants Immunologic Viral Envelope Proteins Antigen medicine Humans Immunology and Allergy 030212 general & internal medicine Ebola Vaccines Ebola virus biology business.industry Immunogenicity Vaccination Australia Hemorrhagic Fever Ebola Saponins Antibodies Neutralizing Virology Healthy Volunteers Titer 030104 developmental biology Infectious Diseases biology.protein Nanoparticles Female Safety business Adjuvant |
| Zdroj: | The Journal of Infectious Diseases. 222:572-582 |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1093/infdis/jiz518 |
| Popis: | Background Ebola virus (EBOV) epidemics pose a major public health risk. There currently is no licensed human vaccine against EBOV. The safety and immunogenicity of a recombinant EBOV glycoprotein (GP) nanoparticle vaccine formulated with or without Matrix-M adjuvant were evaluated to support vaccine development. Methods A phase 1, placebo-controlled, dose-escalation trial was conducted in 230 healthy adults to evaluate 4 EBOV GP antigen doses as single- or 2-dose regimens with or without adjuvant. Safety and immunogenicity were assessed through 1-year postdosing. Results All EBOV GP vaccine formulations were well tolerated. Receipt of 2 doses of EBOV GP with adjuvant showed a rapid increase in anti-EBOV GP immunoglobulin G titers with peak titers observed on Day 35 representing 498- to 754-fold increases from baseline; no evidence of an antigen dose response was observed. Serum EBOV-neutralizing and binding antibodies using wild-type Zaire EBOV (ZEBOV) or pseudovirion assays were 3- to 9-fold higher among recipients of 2-dose EBOV GP with adjuvant, compared with placebo on Day 35, which persisted through 1 year. Conclusions Ebola virus GP vaccine with Matrix-M adjuvant is well tolerated and elicits a robust and persistent immune response. These data suggest that further development of this candidate vaccine for prevention of EBOV disease is warranted. |
| Databáze: | OpenAIRE |
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