Pre-COVID-19 coronavirus antibodies fail to neutralize SARS-CoV-2

Researchers in Austria have shown that antibodies with potent neutralizing activity against a well-established seasonal coronavirus had no neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The team carried out the study to test whether SARS-CoV-2 could potentially be neutralized by antibodies induced by seasonal coronaviruses that are already circulating.

The analysis of intravenous immunoglobulin (IVIG) lots produced against human coronavirus (hCoV) 299E, a long-recognized cause of the common cold, showed high titers of neutralizing antibodies (nAbs) against the 299E virus, but no cross-neutralization effect against SARS-CoV-2.

Thomas Kreil and colleagues from Baxter AG, Vienna, say the finding suggests that nAbs against well-known seasonal coronaviruses cannot neutralize SARS-CoV-2 and that the currently available IVIG lots would not offer any protection against the virus.

A pre-print version of the paper can be accessed on the server bioRxiv*, while the article undergoes peer review.

IVIG lots can be used to protect against known viruses

SARS-CoV-2, the agent that causes coronavirus disease 2019 (COVID-19), belongs to the same family of coronaviruses that includes strains currently circulating seasonally as respiratory viruses.

The thousands of plasma donations previously made by people exposed to such viruses can be pooled to produce IVIG lots containing various antibodies generated against the infectious agents.

These IVIG lots can be used to protect immunocompromised individuals, for example, against circulating viral infections.

Following the emergence of a new virus, detectable levels of antibodies only occur in IVIG lots once a certain proportion of donors have contracted and recovered from the infection. Furthermore, for the lots to offer any protective, neutralizing effect, an even higher proportion of recovered donors is needed.

SARS-CoV-2 belongs to the Coronaviridae family, which includes the hCoVs 229E, NL63, OC43, and HKU1. These agents generally cause a self-limiting and mild illness, although they can also lead to more severe conditions such as pneumonia.

Given the long-term circulation of these hCoVs, by time plasma was pooled from thousands of donors, the IVIG lots contained significant levels of nAbs. However, whether these may cross-react or potentially even neutralize the novel and related SARS-CoV-2 remains unclear.

Some antibody binding assays have demonstrated a certain degree of cross-reactivity, but the more clinically relevant functional neutralization assays have detected no or only minimal levels of cross-neutralization.  

The question is of significant clinical relevance to people with immunodeficiencies

Kreil and colleagues say the question is of particular clinical relevance for people with immune deficiencies (PIDs) since their health depends on whether they can be treated with immunoglobulin preparations that contain neutralizing antibodies against the various pathogens surrounding them.

“SARS-CoV-2 cross-neutralizing antibodies in IVIGs, if they were present, might afford some protection to PIDs, and may even represent a  treatment option for COVID-19 patients,” writes the team.  

Now, the researchers have tested IVIG lots produced from plasma collected in Europe and the US for nAbs against SARS-CoV-2 and the longer circulating hCoV-299E to gauge whether antibodies against existing seasonal coronaviruses might cross-neutralize SARS-CoV-2.

Potent neutralization of hCoV-299E, but not SARS-CoV-2

The analysis showed that the IVIG lots contained high titers of nAbs against hCoV-229E. However, testing the same IVGF lots using a highly specific SARS-CoV-2 neutralization assay showed no cross-neutralization.  

“The finding confirms that the existing hCoV-229E-specific nAbs, as well as the presumably present nAbs against the other seasonal hCoVs, have no cross-neutralizing capacity to SARS-CoV-2,” writes the team.

The researchers say another study testing 21 IVIG lots using a SARS-CoV-2 specific ELISA assay that had previously correlated with a neutralization test, also did not detect the presence of any cross-reacting antibodies.

This, together with the current study, shows that “two experimentally robust studies have not found SARS-CoV-2 nAbs in IVIG lots produced from pre-pandemic plasma,” they write.

Therefore, “currently available IVIGs cannot be expected to afford protection from SARS-CoV-2 infection,” concludes the team.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Sally Robertson

Written by

Sally Robertson

Sally first developed an interest in medical communications when she took on the role of Journal Development Editor for BioMed Central (BMC), after having graduated with a degree in biomedical science from Greenwich University.

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