This article was updated on September 21, 2020 to incorporate comments from Siemens Healthineers.
As Covid-19 antibody tests proliferate, one central question has yet to be answered: does an antibody response actually confer immunity to reinfection? Siemens Healthineers, which is quietly making a name for itself as a company to watch in Covid-19 antibody testing, is collaborating with health protection agencies on both sides of the Atlantic in order to find out.
The German group is to work with the Centers for Disease Control and the Joint Research Centre of the European Commission on a project to identify the minimum antibody titre necessary for a person to be considered immune, and thereby standardise antibody tests for the coronavirus.
While a basic comparison of some antibody tests can be made using figures for sensitivity and specificity, this does not take account of which kind of antibodies they detect. Post-infection, a patient can generate antibodies to various parts of the coronavirus: the spike protein; its separate binding sites, S1 and S2; the receptor-binding domain of the S1 site; or the nucleocapsid protein, for example.
And the various antibody tests available – more than 40 are currently authorised by the US FDA – detect different antibodies. But do all these antibodies protect against reinfection? Do any of them? If some of them do, how high do levels of each have to be? It is these questions that Healthineers, the CDC and the JRC aim to answer.
Titre ye not
The partners intend to develop a reference standard for Sars-CoV-2 assays by determining the neutralisation antibody titre – how much of each antibody confers viral neutralisation – for different manufacturers’ viral antigen targets. Though Healthineers approached the agencies with this idea, the standard itself will be set by the JRC, not Healthineers, the company told Evaluate Vantage, and all antibody test manufacturers would be expected to adopt the resulting framework in the future.
Individuals with levels of an antibody meeting one of these thresholds could, theoretically, be considered immune. And if these standards are recognised internationally, as the presence of US and EU authorities suggests they might be, it could be possible to confer a sort of immunity passport on certain people, allowing them more freedom to travel than those without.
And people need not come by these antibodies via infection. The availability of a Covid-19 vaccine, should this come to pass, will change the game again. Most of the major vaccine candidates that have reached mid- or late-stage development contain – or in the case of the mRNA vaccines, encode – parts or all of the spike protein. This is because antibodies against these antigens are believed to have the best chance of neutralising the virus (Healthineers’ Covid-19 antibody test spikes an interest in vaccines, June 2, 2020).
Those antibody tests that detect the viral proteins used in any successful vaccine will become crucial to establishing immunocompetence in vaccinated people, and determining who might need a booster shot. All of Healthineers’ Covid-19 antibody tests detect antibodies to the S1 receptor-binding domain.
A test that can identify immunocompetent individuals or track vaccination status would be incredibly useful. But no such assay yet exists.
Most of the antibody tests currently available can indicate whether a person has had the virus or not, but no more than that. A few go further: the FDA has authorised two “semi-quantitative” tests, both developed by Healthineers, that can estimate the levels of coronavirus antibodies in a person’s blood. More of these kinds of tests are known to be in development, including one by Roche, but truly quantitative tests, that give a definitive reading of antibody titres, are as yet unavailable.
Healthineers told Vantage that its semi-quantitative technology “does determine those antibody levels, but through the work with the CDC and JRC we will be standardising our assays to the reference materials once they’re available.”
Healthineers is the commercial partner for this initiative because it was the first company with an authorized semi-quantitative assay that targets the spike protein, the group confirmed to Vantage. It is unclear how happy other diagnostics groups will be with any standards that might emerge; still, if the political will to put these standards in place is sufficiently strong, they may have no choice.