Honing In On the COVID Immune Response

With coronavirus vaccine programs in full swing and infections falling, public health officials are now concerned as much with the durability of the vaccinated immune response as they are with contagion mitigation. Hence the tidal wave of commercial, emergency-use-approved assays to quantify antibodies, spike proteins, T cells, secondary biomarkers, etc.

Unfortunately, answers to many questions about COVID-19 immunity remain elusive and may only come to light years from now, if ever. Do we know if herd immunity is achievable through vaccination for this disease? Will immunity be robust and durable, or will we face the need for yearly booster shots? Should millions of people who have been infected with the virus get vaccinated?

Protecting populations through individuals

Irrespective of these issues, quantifying or characterizing immunity during a pandemic is critical for understanding vulnerability to infection of both individuals and populations. Immune status also interests vaccine makers who use pre- and post-vaccination immunology to guide future development efforts.

Although the industry, regulators, and public health officials have been collecting data on vaccination since, one could reasonably assume, mid-2020 we only learned in April 2021 that antibodies induced by the Moderna mRNA shot persist, although in attenuated form, for at least six months. What does that mean? Not very much. The Moderna study, which used just 33 samples, concluded that "antibody titers and assays that best correlate with vaccine efficacy are not currently known."

Actionable testing

A recently released test from Adaptive Biotechnologies is illustrative of how future inter-industry collaborations can advance global health. In March the company received an EUA for a T cell test, T-Detect™ COVID, which quantifies COVID-related T cell activity in recently infected individuals. Conventional assays for current or recent infection measure antibody levels, but antibodies disappear over time. Adaptive's test aims not at antibodies but at T cells, which persist much longer than immunoglobulins.

The company claims this is the first commercial product that detects recent infection in this manner. It was also the first product to emerge from a collaboration between Adaptive and Microsoft.

Most COVID tests focus on either current infection, its immediate aftermath, or immune status. Earlier this year, Aditx Therapeutics introduced an assay that addresses both the virus and the human immunologic response, essentially a twofer. AditxtScore™ Immune Monitoring Platform provides, according to the company, a more complete picture of an individual's COVID-19 infection and immunity status than was previously available using individual assays. The test determines Infection status by evaluating the presence or absence of the virus, and immunity by measuring levels of anti-COVID antibodies and their ability to neutralize the virus. Aditxt is planning to expand the panel to cover cellular immunity as well.

AditxtScore for COVID-19 will be available as a LDT and processed at the AditxtScore Immune Monitoring Center, which will operate as a CLIA-certified reference lab for the test's channel partners, including labs and hospitals. This assures that this much-needed test will be readily available.

"By acting as a reference lab, prospective channel partners can rapidly deploy the service without the need for additional equipment or staffing,” stated Amro Albanna, co-founder and CEO of Aditxt, in the accompanying news release.

Assay evolution

In March, Beckman Coulter received an EUA for its Access SARS-CoV-2 IgG II antibody assay, a semi-quantitative test that quantifies antibody levels in response to previous SARS-CoV-2 infection. This first-generation test provided qualitative and numerical results of antibody levels in arbitrary units, meaning results could be compared for the same individual but became an "apples and oranges" exercise otherwise.

Then, in May, Beckman Coulter significantly improved the IgG II assay by releasing Access SARS-CoV-2 IgG (1st IS), a fully quantitative serologic assay. Unlike IgG II, this iteration is traceable to the newly established WHO reference standard. The new assay reports results in standard units that are globally comparable, with a sensitivity 15 days post-symptoms of 100% and 99.8% specificity.

Conclusion

As the coronavirus pandemic winds down, at least to manageable levels, we will continue to see a shift in focus from the acutely infected to post-infected or post-vaccinated populations. The aim at this juncture should be to learn everything possible about immunity to COVID-19, and apply those lessons to other communicable diseases.

In addition to monitoring immunity status over time in individuals, population-scale testing will allow mapping the seemingly haphazard ebb and flow of infections, illnesses, deaths, and recoveries across time and geography. They will also help answer questions about the effectiveness of vaccines, on a population level, over time. Vaccine manufacturers and governments will no doubt use that information to customize future vaccination programs for diseases other than COVID-19.