Development of a Rapid Diagnostic Test Kit to Detect IgG/IgM Antibody against Zika Virus Using Monoclonal Antibodies to the Envelope and Non-structural Protein 1 of the Virus

Kim, Yeong Hoon; Lee, Jihoo; Kim, Young-Eun; Chong, Chom-Kyu; Pinchemel, Yanaihara; Reisdörfer, Francis; Coelho, Joyce Brito; Dias, Ronaldo Ferreira; Bae, Pan Kee; Gusmão, Zuinara Pereira Maia; Ahn, Hye-Jin; Nam, Ho-Woo

Most ZIKV-infected patients are asymptomatic [4] . On the other hand, most of those who do have them have symptoms that are almost indistinguishable from those of other causes of undifferentiated systemic febrile illness, especially dengue (DENV) and chikungunya virus infections. To further confuse the issue, these infections are also transmitted by the Aedes mosquito and are found in the same regions as ZIKV infections [8] . Furthermore, co-infections with these viruses have also been reported [9, 10] . Additionally, these viral infections could share the transmission routes. ZIKV is primarily transmitted to people through the bite of an infected Aedes mosquito, mainly Aedes aegypti and Aedes albopictus, which are the same mosquitoes that transmit dengue, chikungunya, and yellow fever viruses. Sexual transmission and transmission through laboratory exposure are possible, and it is also theoretically possible through blood transfusion, organ and tissue transplant, fertility treatment, and breast feeding. Interestingly, ZIKV can also be transmitted through other non-vector-borne routes, including sexual intercourse, transplacental transmission, blood product transfusion, and possi-Development of a Rapid Diagnostic Test Kit to Detect IgG/ IgM Antibody against Zika Virus Using Monoclonal Antibodies to the Envelope and Non-structural Protein 1 of the Virus bly exposure to other bodily fluids with high viral loads [8, [11] [12] [13] [14] . Thus, the diagnosis of ZIKV infection cannot be reliably established by clinical features alone. As evidenced by a number of recently emerging viral epidemics, highly sensitive and specific laboratory diagnostics for these infections are essential for infection control measures [15] [16] [17] . Reverse transcriptase-PCR (RT-PCR) has been the most commonly used laboratory diagnostic assay for ZIKV infection worldwide. A number of specific real-time and conventional RT-PCR assays targeting the envelope (E), premembrane (prM), nonstructural proteins 1 (NS1), NS2B, NS3, and NS5 gene coding regions of the ZIKV genome have been described [18] [19] [20] [21] [22] [23] [24] . However, most of these assays were developed before the ZIKV epidemic occurred in the Americas, and there are up to 10 potential nucleotide mismatches between the sequences of the individual assays' primers and current epidemic virus strains [25] . The low sensitivity in these assays may also lead to false-negative results in up to 20-80% of patients, especially those with low viral loads in their blood or urine [25] .