Development and validation of an IgM antibody capture ELISA for early detection of Hendra virus.
Abstract: Zoonotic transmission of Hendra virus (HeV) from primary hosts (pteropid bats) to horses, and, occasionally, onward adventitious spread to humans, is associated with high mortality rates in both affected secondary species. The introduction of an effective recombinant G protein vaccine for use in horses has been a major advance for the suppression of disease risk. However, equine HeV vaccination induces neutralising antibody that is indistinguishable from a post infection immune response when using most first line serology assays (eg. VNT and some ELISAs). We have constructed and evaluated an IgM antibody capture (MAC) ELISA which employs yeast expressed HeV nucleoprotein (N). All other serology tests use the G protein which does not detect early infection and is present in the current Hendra virus vaccine and may cause ambiguity in interpretation of results. Thus, this is the first test developed using a N protein which can successfully detect a recent (primarily within the last four weeks) infection of horses with HeV and is not affected by vaccination induced antibody. Testing a limited panel (21 samples) of post infection sera, a normal serum panel (288 samples) and a post vaccination panel (163 samples), we have estimated DSe to be 100 % (95 % CI, 83.9-100.0 %) and DSp to be 98.4 % (95 % CI, 96.8-99.4 %) relative to assigned serology results (VNT, ELISA and Luminex) for the test panels. The HeV IgM MAC ELISA is intended to supplement other molecular and serology test results, with selective use, and is the only serology test which can provide an indication for recent infection which is otherwise not available.
Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.
Publication Date: 2021-09-21 PubMed ID: 34560109DOI: 10.1016/j.jviromet.2021.114296Google Scholar: Lookup
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Summary
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This study developed and tested a new method for the early detection of Hendra virus in horses. The new method, an IgM antibody capture ELISA that uses yeast-expressed Hendra virus nucleoprotein, can distinguish between infection and vaccination responses, which is not possible with current serology tests.
The Need for a New Diagnostic Method
- The Hendra virus (HeV) is a zoonotic virus, meaning it can be transmitted from animals to humans. In this case, it is primarily transmitted from bats to horses, and occasionally spreads from horses to humans.
- The virus is fatal in many cases, making detection extremely important. A vaccine has been introduced for horses that suppresses the risk of disease, but it causes a problem in diagnosis.
- Existing diagnostic tests (like VNT and certain ELISAs) can’t distinguish between the immune response triggered by an infection and the response to the vaccine. Both stimulate production of a particular protein (the G protein), which the tests detect. But if a horse tests positive, it’s not possible to know whether it’s due to infection or vaccination.
The IgM Antibody Capture ELISA
- The new diagnostic test developed in this study addresses this problem. Instead of detecting the G protein, it looks for antibodies created in response to the Hendra virus nucleoprotein (N).
- The test is an IgM antibody capture (MAC) ELISA: a type of assay that can detect a particular type of antibodies (IgM antibodies), which are produced early on in an infection. As such, the test can detect recent infections.
- This test doesn’t respond to the protein produced by the vaccine, making it easier to distinguish between vaccinated and infected horses.
Performance of the New Test
- The researchers evaluated the performance of the test with a panel of serum samples from horses that had been infected with the Hendra virus or vaccinated against it.
- The test had a diagnostic sensitivity (DSe) of 100% and a diagnostic specificity (DSp) of 98.4%, relative to standard serology tests. This means that the test was able to correctly identify all cases of HeV infection, and correctly identify non-infected cases with an accuracy rate of 98.4%.
- It should be noted though, that the sample size was relatively small, and further testing with larger sample sizes would provide a more accurate estimation of the test’s performance.
Implications of the Research
- The IgM MAC ELISA provides an important supplement to other diagnostic tests for the Hendra virus.
- Because it can detect recent infections and distinguish between vaccination and infection responses, it could greatly improve the ability of veterinarians and public health officials to identify and control outbreaks of the virus.
Cite This Article
APA
McNabb L, Andiani A, Bulavaite A, Zvirbliene A, Sasnauskas K, Lunt R.
(2021).
Development and validation of an IgM antibody capture ELISA for early detection of Hendra virus.
J Virol Methods, 298, 114296.
https://doi.org/10.1016/j.jviromet.2021.114296 Publication
Researcher Affiliations
- Australian Centre for Disease Preparedness (ACDP), Commonwealth Scientific and Industrial Research Organisation (CSIRO), East Geelong, VIC, Australia. Electronic address: leanne.mcnabb@csiro.au.
- University of Melbourne, Werribee Veterinary Clinic, VIC, Australia.
- Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
- Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
- Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
- Australian Centre for Disease Preparedness (ACDP), Commonwealth Scientific and Industrial Research Organisation (CSIRO), East Geelong, VIC, Australia.
MeSH Terms
- Animals
- Antibodies, Viral
- Enzyme-Linked Immunosorbent Assay / methods
- Hendra Virus
- Henipavirus Infections / diagnosis
- Henipavirus Infections / veterinary
- Horses
- Immunoglobulin M
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