Evaluation of 5 Commercially Available Zika Virus Immunoassays

Safronetz, David; Sloan, Angela; Stein, Derek; Mendoza, Emelissa J; Barairo, Nicole; Ranadheera, Charlene; Scharikow, Leanne; Holloway, Kimberly; Robinson, Alyssia; Traykova-Andonova, Maya; Makowski, Kai; Dimitrova, Kristina; Giles, Elizabeth; Hiebert, Joanne; Mogk, Rhonda; Beddome, Sharla; Drebot, Michael A.

doi:10.3201/eid2309.162043

Cited by 75 publications

(70 citation statements)

References 10 publications

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“…To date, there are only three serological assays for ZIKV approved by the U.S. Food and Drug Administration, under an emergency use authorization (56), and a few other commercial tests are available in countries outside the United States or for research purposes. These assays use either NS1, recombinant E, or another, unspecified ZIKV antigen (57). The Centers for Disease Control and Prevention MAC (IgM) ELISA exhibits well-publicized limitations, including false-negative results (58), false-positive results due to cross-reactive antibody from DENV infection (59), and persistence of ZIKV IgM beyond the previously presumed 12-week window (60).…”

Section: Discussionmentioning

confidence: 99%

Development of Envelope Protein Antigens To Serologically Differentiate Zika Virus Infection from Dengue Virus Infection

et al. 2018

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Zika virus (ZIKV) is an emerging flavivirus that can cause birth defects and neurologic complications. Molecular tests are effective for diagnosing acute ZIKV infection, although the majority of infections produce no symptoms at all or present after the narrow window in which molecular diagnostics are dependable. Serology is a reliable method for detecting infections after the viremic period; however, most serological assays have limited specificity due to cross-reactive antibodies elicited by flavivirus infections. Since ZIKV and dengue virus (DENV) widely cocirculate, distinguishing ZIKV infection from DENV infection is particularly important for diagnosing individual cases or for surveillance to coordinate public health responses. Flaviviruses also elicit type-specific antibodies directed to non-cross-reactive epitopes of the infecting virus; such epitopes are attractive targets for the design of antigens for development of serological tests with greater specificity. Guided by comparative epitope modeling of the ZIKV envelope protein, we designed two recombinant antigens displaying unique antigenic regions on domain I (Z-EDI) and domain III (Z-EDIII) of the ZIKV envelope protein. Both the Z-EDI and Z-EDIII antigens consistently detected ZIKV-specific IgG in ZIKV-immune sera but not cross-reactive IgG in DENV-immune sera in late convalescence (>12 weeks postinfection). In contrast, during early convalescence (2 to 12 weeks postinfection), secondary DENV-immune sera and some primary DENV-immune sera cross-reacted with the Z-EDI and Z-EDIII antigens. Analysis of sequential samples from DENV-immune individuals demonstrated that Z-EDIII cross-reactivity peaked in early convalescence and declined steeply over time. The Z-EDIII antigen has much potential as a diagnostic antigen for population-level surveillance and for detecting past infections in patients.

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Section: Discussionmentioning

confidence: 99%

Development of Envelope Protein Antigens To Serologically Differentiate Zika Virus Infection from Dengue Virus Infection

et al. 2018

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“…Previous publications suggested a lower sensitivity of detecting anti-NS1 antibodies, possibly due to their relatively low abundance compared to anti-prM/E antibody in human sera. 15, 22 Our study showed that depletion of anti-prM/E antibodies enhances the sensitivity of NS1 antibody detection. Based on the testing algorithm developed in this study, FP-VLP-MAC-ELISA and NS1-MAC-ELISA had similar PPV and NPV (Table 2).…”

Section: Discussionmentioning

confidence: 68%

“…8 Furthermore, the low sensitivity in detecting anti-NS1 antibodies and the discrepancy in determining sero-positivity between detecting anti-E and anti-NS1 antibodies were continuously reported. 14, 15 Serological cross-reactivity between flaviviruses is common and several recent publications have shown the global efforts trying to resolve this issue to determine the status of ZIKV infection. 13, 16, 17, 18 Although a validated, virus specific sero-diagnostic test is urgently needed, a rigorous evaluation of the assay is required to ensure optimal patient care and accurate epidemiologic surveillance in regions with active transmission of both DENV and ZIKV.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive evaluation of differential serodiagnosis between Zika and dengue viral infection

Chao

Whitney

Davis

et al. 2018

Preprint

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Running headline: differential serodiagnosis of Zika and dengue23 2 Word counts: 250 (abstract); 3499 (text) 24 25 3 Summary 26Diagnostic testing for Zika virus (ZIKV) or dengue virus (DENV) infection can be accomplished by a 27 nucleic acid detection method; however, a negative result does not exclude infection due to the low virus 28 titer during infection depending on the timing of sample collection. Therefore, a ZIKV-or DENV-29 specific serological assay is essential for the accurate diagnosis of patients and to prevent potential 30 severe health outcomes. A retrospective study design with dual approaches of collecting human serum 31 samples for testing was developed. All serum samples were extensively evaluated by using both non-32 infectious virus-like particles (VLPs) and soluble non-structural protein 1 (NS1) in the standard 33 immunoglobulin M (IgM) antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA). Both 34 VLP-and NS1-MAC-ELISAs were found to have similar sensitivity for detecting anti-35 premembrane/envelope and NS1 antibodies from ZIKV-infected patient sera. Group cross reactive 36 (GR)-antibody-ablated homologous fusion peptide-mutated (FP)-VLPs consistently showed higher P/N 37 values than homologous wild-type VLPs. Therefore, FP-VLPs were used to develop the algorithm for 38 differentiating ZIKV from DENV infection. Overall, the sensitivity and specificity of the FP-VLP- 39MAC-ELISA and the NS1-MAC-ELISA were each higher than 80% with no statistical significance. A 40 novel approach to differentiate ZIKV from DENV infection serologically has been developed. The 41 accuracy can reach up to 95% when combining both VLP and NS1 assays. In comparison to current 42 guidelines using neutralization tests to measure ZIKV antibody, this approach can facilitate laboratory 43 screening for ZIKV infection, especially in regions where DENV infection is endemic and capacity for 44 neutralization testing does not exist.45 46 47 48 Zika virus (ZIKV) and dengue virus (DENV), members of the Flaviviridae family, are 49 associated with the resurgence of mosquito-transmitted diseases worldwide. 1 While DENV continues to 50 impose a great economic and public health burden in tropical and subtropical countries, the recent 51 emergence of ZIKV, circulated in Central and South America since 2013, has resulted in terrifying 52 outbreaks with severe health outcomes, including Guillain-Barre syndrome in adults as well as 53 microcephaly, congenital neurologic malformations, and fetal demise in fetuses. 2, 3 Clinically, ZIKV and 54 DENV share similar symptoms of infection, geographical distribution, and transmission cycles between 55 humans and Aedes aegypti mosquitoes. 4 A confirmatory diagnosis can be attained by virus isolation or 56 viral RNA detection in serum and other body fluids, but given the low virus titer during ZIKV infection 57 and the high incidence of mild or asymptomatic ZIKV infections, a ZIKV-specific serological assay is 58 essential to accurately diagnosis the patients who were negative b...

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“…ZIKV, first identified in a forest in Uganda, has recently spread to Asia, Pacific islands, and the American continent, causing serious concern for microcephaly in fetuses [2–4]. Mostly transmitted in urban environments by Aedes aegypti and possibly Aedes albopictus , it has been found in many species of mosquitoes, mostly in Aedes species (31 spp.…”

Section: Introductionmentioning

confidence: 99%

Natural infection and vertical transmission of two flaviviruses (Yellow fever and Zika) in mosquitoes in primary forests in the Brazilian state of Rio de Janeiro (Diptera: Culicidae)

Alencar

et al. 2019

Preprint

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27 Background: Zika virus (ZIKV) was recently introduced in the American continent, 28 probably transmitted by Aedes aegypti and possibly by Ae. albopictus and Culex 29 quinquefasciatus in urban environments. ZIKV represents a known public health 30 problem as it has been involved in newborn cases of congenital microcephaly in South 31 America since 2005. The transmission of this virus in forested areas of other countries 32 and its relative ubiquity in relation to its vectors and reservoirs raises suspicions of its 33 adaptation to non-human modified environments (i.e., natural forests reserve) or on this 34 continent, similar to those seen for Yellow fever virus (YFV). The objective of this 35 work was to have an epidemiological monitoring tool mapping insects as well as 36 circulating arboviruses in wild areas with low human interference. This study was based 37 on the history of the insect flavivirus spreading cycle. Methods/Principal Findings: 38 Using a previously described sensitive PCR-based assay to assess the conserved NS5 39 region of the Flavivirus genus, both YFV partial genome and ZIKV were found in pools 40 of Aedes albopictus, a sylvatic mosquito adapted to human-modified environments, and 41 in Haemagogus leucocelaenus, a sylvatic mosquito. Conclusions: This is the first report 42 of natural infection by ZIKV in mosquitoes in a sylvatic environment on the American 43 continent. The wide distribution of these mosquitoes is probably important in the 44 transmission of ZIKV. Vertical transmission indicates a higher efficiency for the 45 maintenance and transmission of the virus in nature as well as the presence of the ZIKV 46 in permanent character in the forest areas as it occurs with the YFV thus making more 47 difficult the prevention of new cases of Zika in humans.48 49 50 3 51 Author Summary 52 Arboviruses are diseases transmitted by arthropod vectors, hence the origin of the term 53 ARthropod BOrne VIRUS, which is adopted since 1942. This work had as objective to 54 survey the circulating insects as well as to detect the presence of viruses in them. 55 Arboviruses circulate between insects and vertebrate hosts, having importance for 56 promoting diseases in humans and animals. The diseases most known at the time, due to 57 the recent cases reported by South America, are Dengue, Zika, Yellow Fever and 58 Chikungunya. For this study, we used appropriate traps to collect the insects and their 59 eggs in wild areas where there is little human interference. After collection, mosquitoes 60 and / or eggs were identified and separated as to the source and species. The eggs were 61 kept in laboratory conditions for the hatching of new insects. All the insects obtained 62 were separated into pools to be macerated and thus extract the RNA from the viruses to 63 be studied. Using molecular biology techniques, in our case the RT-PCR (Reverse 64 Transcriptase Polymerase Chain Reaction), we amplified the RNA and in sequentially, 65 we performed the sequencing reaction. With sequencing, it is possible to iden...

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Evaluation of 5 Commercially Available Zika Virus Immunoassays

Cited by 75 publications

References 10 publications

Development of Envelope Protein Antigens To Serologically Differentiate Zika Virus Infection from Dengue Virus Infection

Development of Envelope Protein Antigens To Serologically Differentiate Zika Virus Infection from Dengue Virus Infection

Comprehensive evaluation of differential serodiagnosis between Zika and dengue viral infection

Natural infection and vertical transmission of two flaviviruses (Yellow fever and Zika) in mosquitoes in primary forests in the Brazilian state of Rio de Janeiro (Diptera: Culicidae)

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