Serological diagnosis of Zika virus infections

EUROIMMUN AG announces option agreement on Zika virus serology

EUROIMMUN and Roche announced that they have entered into an option agreement under which Roche gains access to intellectual property in the field of Zika virus immunodiagnostics assigned to EUROIMMUN.

Press Release

NEW: EUROIMMUN Anti-Zika Virus ELISA (IgA) and (IgAM)

Anti-Zika virus IgA may indicate an acute infection in anti-Zika virus IgM-negative patients

Especially in secondary flavivirus infections specific IgM - the classical marker of acute infection – is often found at low titer, sometimes being even undetectable, while synthesis of specific IgG is rapidly stimulated. Shortly after infection, the IgG titer then levels off at moderate concentration, indistinguishable from IgG titers in convalescent infections. Similar situations have also been observed in patients with Zika virus (ZIKV) infections, recently, making it difficult to discriminate between an acute secondary and a past infection. Since ZIKV is suspected to be associated with major neurological consequences (Guillan-Barré syndrome, microcephaly in newborns), diagnosis of acute infections though is highly crucial. We analysed the course of anti-ZIKV IgA, IgM and IgG titers in two confirmed patients for whom sequential serum samples were available asking whether IgA as alternative to IgM could indicate an acute phase of infection. Furthermore, we investigated the diagnostic benefit of an ELISA for combined detection of anti-ZIKV NS1 IgA and IgM.

Testing anti-Zika virus NS1 IgA additionally to IgM increases sensitivity in acutely infected patients from regions endemic for flaviviruses

General Information

ELISA and indirect immunofluorescence tests (IIFT) have been developed for sensitive and specific detection of antibodies against Zika virus in patient serum samples. The assays are suitable for diagnosing acute infections as well as for disease surveillance. In particular, serological analysis can aid the differentiation of infections with Zika virus, dengue virus and chikungunya virus, which manifest with similar symptoms and are endemic in much the same geographic regions.
Serological tests provide a much longer window for diagnosis than direct detection methods. Detection of the virus by RT-PCR is only effective during the viraemic phase within the first week after onset of symptoms, and may already be negative by the time a patient consults their doctor. Anti-Zika virus antibodies appear around day 4 to 7 after symptom onset. IgM antibodies reach their peak after two to three weeks and remain detectable for several months, while IgG are assumed to persist life-long. The detection of specific IgM antibodies or a significant rise in the specific IgG titer in a pair of samples taken at least two weeks apart is evidence of an acute infection.

EUROIMMUN test systems for the diagnosis of Zika virus infections

ELISA

Anti-Zika Virus ELISA (IgA or IgM or IgG or IgAM) provide fully automated antibody detection using microplates coated with a recombinant protein from Zika virus. This highly specific antigen avoids cross-reactivity with other flaviviruses. Preliminary data from panels of serologically well characterised sera indicate that there is no cross-reactivity with flaviruses like dengue, West Nile and Japanese encephalitis viruses. Larger studies are underway to confirm this.

IgA

IgM

IgG

IgAM

IIFT

Anti-Zika Virus IIFT (IgM or IgG) utilise Zika virus-infected cells as the antigenic substrate. Positive and negative results are evaluated by fluorescence microscopy. With the Arbovirus Fever Mosaic 2 the Zika virus substrate is incubated in parallel with substrates for chikungunya virus and dengue virus serotypes 1 to 4. This BIOCHIP combination can help in differential diagnostic delimitation of Zika, dengue and chikungunya virus infections. Due to the use of whole virus particles, cross reactivities between flavivirus antibodies such as dengue and Zika virus can occur.

Serological differential diagnosis using IFA technology