Design, development, and validation of multi-epitope proteins for serological diagnosis of Zika virus infections and discrimination from dengue virus seropositivity

• Published in: PLoS neglected tropical diseases Vol. 18; no. 4; p. e0012100
• Main Authors: Pereira, Samille Henriques, Sá Magalhães Serafim, Mateus, Moraes, Thaís de Fátima Silva, Zini, Nathalia, Abrahão, Jônatas Santos, Nogueira, Maurício Lacerda, Coelho Dos Reis, Jordana Grazziela Alves, Bagno, Flávia Fonseca, da Fonseca, Flávio Guimarães
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-04-2024; Public Library of Science (PLoS)
• Subjects: Antibodies; Antibodies, Viral; Antigens; Arboviruses; Binding sites; Biology and life sciences; Chikungunya Fever; Chikungunya virus; Cross-reactivity; Dengue; Dengue fever; Dengue Virus; Diagnosis; Differential diagnosis; Epidemics; Epitopes; Flaviviridae; Gene expression; Health aspects; Human diseases; Humans; Immunoassay; Immunoglobulin G; Infections; Medicine and Health Sciences; Microencephaly; Patients; Proteins; Recombinants; Serology; Signs and symptoms; Testing; Vector-borne diseases; Virology; Viruses; Zika virus; Zika Virus - genetics; Zika Virus Infection - diagnosis; Brazil; United States > US; Massachusetts; Illinois; Missouri; Chicago Illinois; California
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0012100

Zika virus (ZIKV), an arbovirus from the Flaviviridae family, is the causative agent of Zika fever, a mild and frequent oligosymptomatic disease in humans. Nonetheless, on rare occasions, ZIKV infection can be associated with Guillain-Barré Syndrome (GBS), and severe congenital complications, such as microcephaly. The oligosymptomatic disease, however, presents symptoms that are quite similar to those observed in infections caused by other frequent co-circulating arboviruses, including dengue virus (DENV). Moreover, the antigenic similarity between ZIKV and DENV, and even with other members of the Flaviviridae family, complicates serological testing due to the high cross-reactivity of antibodies. Here, we designed, produced in a prokaryotic expression system, and purified three multiepitope proteins (ZIKV-1, ZIKV-2, and ZIKV-3) for differential diagnosis of Zika. The proteins were evaluated as antigens in ELISA tests for the detection of anti-ZIKV IgG using ZIKV- and DENV-positive human sera. The recombinant proteins were able to bind and detect anti-ZIKV antibodies without cross-reactivity with DENV-positive sera and showed no reactivity with Chikungunya virus (CHIKV)- positive sera. ZIKV-1, ZIKV-2, and ZIKV-3 proteins presented 81.6%, 95%, and 66% sensitivity and 97%, 96%, and 84% specificity, respectively. Our results demonstrate the potential of the designed and expressed antigens in the development of specific diagnostic tests for the detection of IgG antibodies against ZIKV, especially in regions with the circulation of multiple arboviruses.