Glucopyranosyl lipid adjuvant enhances immune response to Ebola virus-like particle vaccine in mice |
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| Affiliation: | 1. United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, MD 21702, USA;2. Infectious Disease Research Institute, 1616 Eastlake Ave E, Suite 400, Seattle, WA 98102, USA;1. Fred Hutch HIV Vaccine Trials Network, United States;2. Fred Hutch, Statistical Center for HIV/AIDS Research and Prevention, United States;3. Bridge HIV, San Francisco Department of Public Health, United States;4. NIH/NIAID, United States;1. Department of Dermatology, Medical University Vienna (MUW), Austria;2. Department of Pathology, Johns Hopkins University, Baltimore, MD, USA;1. Center for Virology & Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA;2. Infectious Disease Research Institute, Seattle, WA 98102, USA;3. Crucell, 2301 CA Leiden, The Netherlands;4. Division of Molecular Medicine, Children''s Hospital, Boston, MA 02115, USA;5. Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA;6. Ragon Institute of MGH, MIT and Harvard, Boston, MA 02114, USA;1. Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD, USA;2. Vaccine Platform Group, MedImmune, Gaithersburg, MD, USA;3. Statistical Sciences, MedImmune, Gaithersburg, MD, USA;1. Department of Infectious Disease and Global Health, Tufts University Cummings School of Veterinary Medicine, 200 Westboro Road, North Grafton, MA 01536, USA;2. Department of Microbiology and Molecular Genetics, Oklahoma State University, 307 Life Sciences East, Stillwater, OK 74075, USA;2. Pasteur Institut, Paris, France;3. IDRI, Seattle, USA;4. Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland |
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| Abstract: | The identification of adjuvants that promote lasting antigen-specific immunity and augment vaccine efficacy are integral to the development of new protein-based vaccines. The Ebola virus-like particle (VLP) vaccine expressing Ebola virus glycoprotein (GP) and matrix protein (VP40) was used in this study to evaluate the ability of TLR4 agonist glucopyranosyl lipid adjuvant (GLA) formulated in a stable emulsion (SE) to enhance immunogenicity and promote durable protection against mouse-adapted Ebola virus (ma-EBOV). Antibody responses and Ebola-specific T cell responses were evaluated post vaccination. Survival analysis after lethal ma-EBOV challenge was performed 4 weeks and 22 weeks following final vaccination. GLA-SE enhanced EBOV-specific immunity and resulted in long-term protection against challenge with ma-EBOV infection in a mouse model. Specifically, GLA-SE elicited Th1-skewed antibodies and promoted the generation of EBOV GP-specific polyfunctional T cells. These results provide further support for the utility of TLR4 activating GLA-SE-adjuvanted vaccines. |
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