A dose-dependent plasma signature of the safety and immunogenicity of the rVSV-Ebola vaccine in Europe and Africa.

Autor:	Huttner A; Infection Control Program, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.; Division of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.; Center for Vaccinology, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland., Combescure C; Division of Clinical Epidemiology, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland., Grillet S; World Health Organization Collaborating Center for Vaccine Immunology, Faculty of Medicine, Geneva, Switzerland., Haks MC; Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands., Quinten E; Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands., Modoux C; Division of Immunology and Allergy, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland., Agnandji ST; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon.; Institut für Tropenmedizin, Universitätsklinikum Tübingen, and German Center for Infection Research, Tübingen, Germany., Brosnahan J; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon., Dayer JA; Division of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland., Harandi AM; Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden., Kaiser L; Division of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland., Medaglini D; Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy.; Sclavo Vaccines Association, Siena, Italy., Monath T; NewLink Genetics Corp., 94 Jackson Road, Devens, MA 01439, USA., Roux-Lombard P; Division of Immunology and Allergy, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland., Kremsner PG; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon.; Institut für Tropenmedizin, Universitätsklinikum Tübingen, and German Center for Infection Research, Tübingen, Germany., Ottenhoff TH; Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands., Siegrist CA; Center for Vaccinology, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. claire-anne.siegrist@unige.ch.; World Health Organization Collaborating Center for Vaccine Immunology, Faculty of Medicine, Geneva, Switzerland.
Jazyk:	angličtina
Zdroj:	Science translational medicine [Sci Transl Med] 2017 Apr 12; Vol. 9 (385).
DOI:	10.1126/scitranslmed.aaj1701
Abstrakt:	The 2014-2015 Ebola epidemic affected several African countries, claiming more than 11,000 lives and leaving thousands with ongoing sequelae. Safe and effective vaccines could prevent or limit future outbreaks. The recombinant vesicular stomatitis virus-vectored Zaire Ebola (rVSV-ZEBOV) vaccine has shown marked immunogenicity and efficacy in humans but is reactogenic at higher doses. To understand its effects, we examined plasma samples from 115 healthy volunteers from Geneva who received low-dose (LD) or high-dose (HD) vaccine or placebo. Fifteen plasma chemokines/cytokines were assessed at baseline and on days 1, 2 to 3, and 7 after injection. Significant increases in monocyte-mediated MCP-1/CCL2, MIP-1β/CCL4, IL-6, TNF-α, IL-1Ra, and IL-10 occurred on day 1. A signature explaining 68% of cytokine/chemokine vaccine-response variability was identified. Its score was higher in HD versus LD vaccinees and was associated positively with vaccine viremia and negatively with cytopenia. It was higher in vaccinees with injection-site pain, fever, myalgia, chills, and headache; higher scores reflected increasing severity. In contrast, HD vaccinees who subsequently developed arthritis had lower day 1 scores than other HD vaccinees. Vaccine dose did not influence the signature despite its influence on specific outcomes. The Geneva-derived signature associated strongly (ρ = 0.97) with that of a cohort of 75 vaccinees from a parallel trial in Lambaréné, Gabon. Its score in Geneva HD vaccinees with subsequent arthritis was significantly lower than that in Lambaréné HD vaccinees, none of whom experienced arthritis. This signature, which reveals monocytes' critical role in rVSV-ZEBOV immunogenicity and safety across doses and continents, should prove useful in assessments of other vaccines. (Copyright © 2017, American Association for the Advancement of Science.)
Databáze:	MEDLINE
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