High specificity and sensitivity of Zika EDIII-based ELISA diagnosis highlighted by a large human reference panel

Autor: Cyril Badaut, Véronique Chastres, Bernard Tenebray, Jessica Denis, Sébastien Briolant, Annabelle Garnier, Isabelle Leparc-Goffart, Patrick Gravier, Sarah Attoumani, Franck de Laval, Gilda Grard, Bruno Coutard
Přispěvatelé: Unité de Biothérapies anti-Infectieuses et Immunité [Brétigny-sur-Orge], Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Centre National de Référence des Arbovirus [Marseille], Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA)-Unité d'Arbovirologie [Marseille], Hôpital d'Instruction des Armées Laveran, Service de Santé des Armées-Service de Santé des Armées-Hôpital d'Instruction des Armées Laveran, Service de Santé des Armées-Service de Santé des Armées, Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Parasitologie et d’Entomologie, Département des Maladies Infectieuses-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Centre d'Epidémiologie et de Santé Public des Armées, Service de Santé des Armées, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), This work was partially supported by the European Union’s Horizon 2020 Research and Innovation Programme, under ZIKAlliance Grant Agreement no. 734548, as well as by the European Virus Archive goes global (EVAg) project, under Grant Agreement no. 653316, and partially funded by the Direction Générale de l’Armement and the Service de Santé des Armées, Biomedef PDH-2-NRBC-2-B2-205 and PDH-2-NRBC-2-B-2111, European Project: 734548,ZIKAlliance(2016), European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), Institut de Recherche Biomédicale des Armées (IRBA), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département des Maladies Infectieuses-Institut de Recherche Biomédicale des Armées (IRBA), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Unité de Parasitologie et d'Entomologie [Marseille], Département des Maladies Infectieuses [Marseille], Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA)-Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), Centre d'épidémiologie et de santé publique des armées (CESPA), Unité Perception [Brétigny-sur-Orge], Département Neurosciences et Sciences Cognitives [Brétigny-sur-Orge], Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche Biomédicale des Armées (IRBA), This work was partially supported by the European Union’s Horizon 2020 Research and Innovation Programme, under ZIKAlliance Grant Agreement no. 734548, as well as by the European Virus Archive goes global (EVAg) project, under Grant Agreement no. 653316, and partially funded by the Direction Générale de l’Armement and the Service de Santé des Armées, Biomedef PDH-2-NRBC-2-B2-205 and PDH-2-NRBC-2-B-2111., coutard, bruno, A global alliance for Zika virus control and prevention - ZIKAlliance - 2016-10-01 - 2019-09-30 - 734548 - VALID, European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Serotype
RNA viruses
Male
Physiology
viruses
RC955-962
Dengue virus
medicine.disease_cause
Pathology and Laboratory Medicine
Antibodies
Viral
Cross-reactivity
Biochemistry
Zika virus
Serology
Dengue
Mice
0302 clinical medicine
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Immune Physiology
Arctic medicine. Tropical medicine
Medicine and Health Sciences
Enzyme-Linked Immunoassays
Child
Cross Reactivity
Aged
80 and over
[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Immune System Proteins
biology
Zika Virus Infection
virus diseases
Middle Aged
Recombinant Proteins
3. Good health
Infectious Diseases
Medical Microbiology
Viral Pathogens
Child
Preschool
Viruses
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
Antibody
Pathogens
Public aspects of medicine
RA1-1270
Research Article
Adult
Adolescent
030231 tropical medicine
Immunology
Enzyme-Linked Immunosorbent Assay
Research and Analysis Methods
Microbiology
Sensitivity and Specificity
Virus
Antibodies
03 medical and health sciences
medicine
Animals
Humans
Immunoassays
Microbial Pathogens
Aged
Biology and life sciences
Flaviviruses
Public Health
Environmental and Occupational Health
Organisms
Proteins
Infant
Zika Virus
Dengue Virus
biology.organism_classification
Virology
030104 developmental biology
Polyclonal antibodies
Immunoglobulin G
biology.protein
Immunologic Techniques
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Arboviruses
Zdroj: PLoS Neglected Tropical Diseases
PLoS Neglected Tropical Diseases, 2019, 13 (9), pp.e0007747. ⟨10.1371/journal.pntd.0007747⟩
PLoS Neglected Tropical Diseases, Public Library of Science, 2019, 13 (9), pp.e0007747. ⟨10.1371/journal.pntd.0007747⟩
PLOS Neglected Tropical Diseases
PLoS Neglected Tropical Diseases, Vol 13, Iss 9, p e0007747 (2019)
ISSN: 1935-2727
1935-2735
Popis: Background Zika virus (ZIKV) and Dengue virus (DENV) are often co-endemic. The high protein-sequence homology of flaviviruses renders IgG induced by and directed against them highly cross-reactive against their antigen(s), as observed on a large set of sera, leading to poorly reliable sero-diagnosis. Methods We selected Domain III of the ZIKV Envelope (ZEDIII) sequence, which is virus specific. This recombinant domain was expressed and purified for the specific detection of ZEDIII-induced IgG by ELISA from ZIKV-RT-PCR-positive, ZIKV-IgM-positive, flavivirus-positive but ZIKV-negative, or flavivirus-negative sera. We also assessed the reactivity of ZEDIII-specific human antibodies against EDIII of DENV serotype 4 (D4EDIII) as a specific control. Sera from ZEDIII-immunized mice were also tested. Results Cross-reactivity of IgG from 5,600 sera against total inactivated DENV or ZIKV was high (71.0% [69.1; 72.2]), whereas the specificity and sensitivity calculated using a representative cohort (242 sera) reached 90% [84.0; 95.8] and 92% [84.5; 99.5], respectively, using a ZEDIII-based ELISA. Moreover, purified human IgG against D2EDIII or D4EDIII did not bind to ZEDIII and we observed no D4EDIII reactivity with ZIKV-induced mouse polyclonal IgGs. Conclusions We developed a ZEDIII-based ELISA that can discriminate between past or current DENV and ZIKV infections, allowing the detection of a serological scar from other flaviviruses. This could be used to confirm exposure of pregnant women or to follow the spread of an endemic disease.
Author summary The serological detection of Zika virus (ZIKV) is a challenge, as ZIKV infection generally leads to an immune response with a high level of cross reactivity against related viruses, such as Dengue virus. Although seroneutralization assays are the gold-standard to address specificity, a rapid and cost-effective detection assay with good specificity and sensitivity could be used for first-line screening. We used a large cohort to define a set of human reference sera to validate an ELISA based on a recombinant ZIKV antigen. The assay showed 90% specificity and 92% sensitivity, providing a good basis for the development of diagnostic assays. Characterization of both DENV-EDIII-purified human and murine IgG induced by ZIKV infection or ZEDIII, respectively, confirmed the good specificity of the antigen.
Databáze: OpenAIRE
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