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

• Published in: PLoS neglected tropical diseases 2019-09, Vol.13 (9), p.e0007747-e0007747
• Main Authors: Denis, Jessica, Attoumani, Sarah, Gravier, Patrick, Tenebray, Bernard, Garnier, Annabelle, Briolant, Sébastien, de Laval, Franck, Chastres, Véronique, Grard, Gilda, Leparc-Goffart, Isabelle, Coutard, Bruno, Badaut, Cyril
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Amino acid sequence; Animals; Antibodies; Antibodies, Viral - blood; Antigen-antibody reactions; Antigens; Biology and life sciences; Child; Child, Preschool; Cohorts; Cross-reactivity; Dengue; Dengue - diagnosis; Dengue - immunology; Dengue fever; Dengue virus; Dengue Virus - immunology; Detection; Diagnosis; Disease transmission; DNA; ELISA; Enzyme-linked immunosorbent assay; Enzyme-Linked Immunosorbent Assay - methods; Epidemics; Female; Guillain-Barre syndrome; Homology; Human diseases; Humans; Immunization; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Infant; Infections; Infectious diseases; Life Sciences; Male; Medicine and Health Sciences; Methods; Mice; Microbiology and Parasitology; Middle Aged; Miscarriage; Nucleotide sequence; PCR; Polymerase chain reaction; Pregnancy; Pregnant women; Reactivity; Recombinants; Research and Analysis Methods; Sensitivity; Sensitivity and Specificity; Sequencing; Specificity; Supervision; Tropical diseases; Vector-borne diseases; Viral diseases; Virology; Viruses; Women; Zika virus; Zika Virus - immunology; Zika virus infection; Zika Virus Infection - diagnosis; Zika Virus Infection - immunology; Zika Virus Infection - virology
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0007747

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. 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. 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. 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.