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Spot the difference-development of a syndrome based protein microarray for specific serological detection of multiple flavivirus infections in travelers.

Cleton NB, Godeke GJ, Reimerink J, Beersma MF, Doorn HR, Franco L, Goeijenbier M, Jimenez-Clavero MA, Johnson BW, Niedrig M, Papa A, Sambri V, Tami A, Velasco-Salas ZI, Koopmans MP, Reusken CB - PLoS Negl Trop Dis (2015)

Bottom Line: Sera from clinical flavivirus patients were used for primary development of the protein microarray.Results show a high IgG and IgM sensitivity and specificity for individual NS1 antigens, and limited cross reactivity, even within serocomplexes.Based on these data, multiplex NS1-based protein microarray is a promising tool for surveillance and diagnosis of flaviviruses.

View Article: PubMed Central - PubMed

Affiliation: Erasmus Medical Centre, Viroscience Department, Rotterdam, The Netherlands; National Institute for Public Health and Environment, Center for Infectious Diseases Research and Screening, Bilthoven, The Netherlands.

ABSTRACT

Background: The family Flaviviridae, genus Flavivirus, holds many of the world's most prevalent arboviral diseases that are also considered the most important travel related arboviral infections. In most cases, flavivirus diagnosis in travelers is primarily based on serology as viremia is often low and typically has already been reduced to undetectable levels when symptoms set in and patients seek medical attention. Serological differentiation between flaviviruses and the false-positive results caused by vaccination and cross-reactivity among the different species, are problematic for surveillance and diagnostics of flaviviruses. Their partially overlapping geographic distribution and symptoms, combined with increase in travel, and preexisting antibodies due to flavivirus vaccinations, expand the need for rapid and reliable multiplex diagnostic tests to supplement currently used methods.

Goal: We describe the development of a multiplex serological protein microarray using recombinant NS1 proteins for detection of medically important viruses within the genus Flavivirus. Sera from clinical flavivirus patients were used for primary development of the protein microarray.

Results: Results show a high IgG and IgM sensitivity and specificity for individual NS1 antigens, and limited cross reactivity, even within serocomplexes. In addition, the serology based on this array allows for discrimination between infection and vaccination response for JEV vaccine, and no cross-reactivity with TBEV and YFV vaccine induced antibodies when testing for antibodies to other flaviviruses.

Conclusion: Based on these data, multiplex NS1-based protein microarray is a promising tool for surveillance and diagnosis of flaviviruses.

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Related in: MedlinePlus

The serogroup classification of the Flavivirus genus of arboviruses used.Shaded boxes indicate antigens and antibodies used in this validation. Viruses with an * indicate that human vaccines are available for this virus.
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pntd.0003580.g001: The serogroup classification of the Flavivirus genus of arboviruses used.Shaded boxes indicate antigens and antibodies used in this validation. Viruses with an * indicate that human vaccines are available for this virus.

Mentions: The genus is divided into serocomplexes that are distinguished based on neutralizing antibody reactivity (Fig. 1). The amino acid homology of the envelope (E) protein (which is the immunodominant antigen for neutralizing antibody assays) ranges from 40–50% between serocomplexes and 70–80% for virus species within a serocomplex.[5, 8] Antibodies to flaviviruses are known to cross-react extensively within, and to a certain extent between, serocomplexes when using traditional antibody assays.[9–12] Cross-reactivity occurs also if patients have been vaccinated against flaviviruses such as yellow fever virus (YFV), tick-borne encephalitis virus (TBEV) and/or Japanese encephalitis virus (JEV) or after secondary infection with a different flavivirus.[9, 10, 13]


Spot the difference-development of a syndrome based protein microarray for specific serological detection of multiple flavivirus infections in travelers.

Cleton NB, Godeke GJ, Reimerink J, Beersma MF, Doorn HR, Franco L, Goeijenbier M, Jimenez-Clavero MA, Johnson BW, Niedrig M, Papa A, Sambri V, Tami A, Velasco-Salas ZI, Koopmans MP, Reusken CB - PLoS Negl Trop Dis (2015)

The serogroup classification of the Flavivirus genus of arboviruses used.Shaded boxes indicate antigens and antibodies used in this validation. Viruses with an * indicate that human vaccines are available for this virus.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4359159&req=5

pntd.0003580.g001: The serogroup classification of the Flavivirus genus of arboviruses used.Shaded boxes indicate antigens and antibodies used in this validation. Viruses with an * indicate that human vaccines are available for this virus.
Mentions: The genus is divided into serocomplexes that are distinguished based on neutralizing antibody reactivity (Fig. 1). The amino acid homology of the envelope (E) protein (which is the immunodominant antigen for neutralizing antibody assays) ranges from 40–50% between serocomplexes and 70–80% for virus species within a serocomplex.[5, 8] Antibodies to flaviviruses are known to cross-react extensively within, and to a certain extent between, serocomplexes when using traditional antibody assays.[9–12] Cross-reactivity occurs also if patients have been vaccinated against flaviviruses such as yellow fever virus (YFV), tick-borne encephalitis virus (TBEV) and/or Japanese encephalitis virus (JEV) or after secondary infection with a different flavivirus.[9, 10, 13]

Bottom Line: Sera from clinical flavivirus patients were used for primary development of the protein microarray.Results show a high IgG and IgM sensitivity and specificity for individual NS1 antigens, and limited cross reactivity, even within serocomplexes.Based on these data, multiplex NS1-based protein microarray is a promising tool for surveillance and diagnosis of flaviviruses.

View Article: PubMed Central - PubMed

Affiliation: Erasmus Medical Centre, Viroscience Department, Rotterdam, The Netherlands; National Institute for Public Health and Environment, Center for Infectious Diseases Research and Screening, Bilthoven, The Netherlands.

ABSTRACT

Background: The family Flaviviridae, genus Flavivirus, holds many of the world's most prevalent arboviral diseases that are also considered the most important travel related arboviral infections. In most cases, flavivirus diagnosis in travelers is primarily based on serology as viremia is often low and typically has already been reduced to undetectable levels when symptoms set in and patients seek medical attention. Serological differentiation between flaviviruses and the false-positive results caused by vaccination and cross-reactivity among the different species, are problematic for surveillance and diagnostics of flaviviruses. Their partially overlapping geographic distribution and symptoms, combined with increase in travel, and preexisting antibodies due to flavivirus vaccinations, expand the need for rapid and reliable multiplex diagnostic tests to supplement currently used methods.

Goal: We describe the development of a multiplex serological protein microarray using recombinant NS1 proteins for detection of medically important viruses within the genus Flavivirus. Sera from clinical flavivirus patients were used for primary development of the protein microarray.

Results: Results show a high IgG and IgM sensitivity and specificity for individual NS1 antigens, and limited cross reactivity, even within serocomplexes. In addition, the serology based on this array allows for discrimination between infection and vaccination response for JEV vaccine, and no cross-reactivity with TBEV and YFV vaccine induced antibodies when testing for antibodies to other flaviviruses.

Conclusion: Based on these data, multiplex NS1-based protein microarray is a promising tool for surveillance and diagnosis of flaviviruses.

Show MeSH
Related in: MedlinePlus