Key Antibody Targets Of SARS-CoV-2 Identified

Researchers in Hong Kong have discovered that focusing on antibodies against ORF3b and ORF8 could lead to a rapid antibody test that is both highly sensitive and specific.

AsianScientist (Sep. 1, 2020) – Scientists in Hong Kong have identified two key targets recognized by antibodies against SARS-CoV-2. Their findings, published in Nature Immunology, could be used to make antibody-based COVID-19 tests more accurate.

While reverse transcriptase polymerase chain reaction (RT-PCR) remains the gold standard for COVID-19 diagnosis, serology-based tests—which detect the presence of antibodies against SARS-CoV-2—are urgently needed to contain the outbreak. Antibody testing allows researchers to define the true extent of infection in the community and confirm diagnosis in suspected patients; it is also needed for the evaluation of vaccines.

To date, SARS-CoV-2 antibody testing has been focussed on two virus proteins: the spike protein, as it correlates with neutralizing capacity of the serum; and the nucleocapsid protein, as it is made abundantly by the virus and thus more likely to elicit detectable responses. Both proteins have potential problems with false positive reactions due to cross reactivity with antibodies to other human coronaviruses which are common in the population.

Instead, researchers from the University of Hong Kong (HKU) used a tool originally designed for screening cancer and new pathogen antigens to identify the main targets of the antibody response to SARS-CoV-2. Called luciferase immunoprecipitation system (LIPS), the assay used 15 different SARS-CoV-2 proteins labelled with a reporter enzyme to ‘pull down’ patient antibodies specific to viral proteins.

The team led by study corresponding author Assistant Professor Sophie Valkenberg of HKU found that COVID-19 patients had high levels of antibodies against six SARS-CoV-2 proteins: NSP1, ORF3a, ORF3b, ORF7a, ORF7b and ORF8. In particular, the greatest difference in antibody levels between COVID-19 samples and negative controls was seen for ORF3b and ORF8. Because these two proteins are unique to SARS-CoV-2, developing antibody tests focused on ORF3b and ORF8 could avoid the problem of cross-reactivity with other ‘common cold’ human coronaviruses.

By testing patient samples for both ORF3b and ORF8 antibodies, the researchers were able to develop a test that identified 96.5 percent of COVID-19 samples at both early and late timepoints of disease with 99.5 percent specificity.

Given the high sensitivity and specificity of this combined test, the authors concluded that their findings could be used to improve antibody-based tests for COVID-19 and enhance the development of second-generation diagnostic tests.

The article can be found at: Hachim et al. (2020) ORF8 and ORF3b Antibodies are Accurate Serological Markers of Early and Late SARS-CoV-2 Infection.


Source: University of Hong Kong; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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