To enable an effective vaccination strategy, we advocate for the use of accessible, automated, high-throughput SARS-CoV-2 serology testing to help confirm efficacy and promote public health. Siemens Healthineers formulated a position paper based on input from experts in the infectious disease, immunology and vaccine development fields and the currently available body of literature.
"The position statement that you have here is timely. We need to have this discussion and preparation ahead of vaccinating the general population. Serology status is incredibly important due to asymptomatic carriers, and as these vaccines are introduced the need for robust neutralizing antibody testing would become even more important to understand where we are both before and after vaccination."
Ankur Mutreja, PhD
University of Cambridge (UK), Department of Medicine/CITIID
Serology tests can inform vaccination utilization and status of vaccine response at multiple junctures:
- Data to establish a threshold for protection or immunity
- Determination of appropriate vaccine recipients, especially with limited vaccine availability
- Post-vaccination initial response1
- Duration of vaccination response2
Appropriate characteristics of a serology assay in the assessment of need to vaccinate and vaccine response:
- Quantitative results
- Spike protein receptor-binding domain (S1 RBD) neutralizing IgG antibody detection
- Very high specificity (≥99.5%)
Neutralizing Antibodies: Why the Spike Protein?
SARS-CoV-2 serology assays that utilize the receptor-binding domain (RBD) of the S1 spike antigen detect neutralizing antibodies that block the virus entry into cells.3-8 S1-RBD-specific assays are likely to prove advantageous over S1 and whole spike, especially if using a quantitative assay, as neutralizing versus binding antibodies might be expected to be enriched and therefore better correlate to immunity.
The utilization of the S1-RBD is aligned with the multiple vaccines in development that target or include the SARS-CoV-2 S1 RBD, with the goal of producing neutralizing (and therefore likely protective) antibodies in vaccinated subjects.9 The spike protein and particularly the RBD are the most common target of vaccine designs.
Webinar: SARS-CoV-2 Serology Testing in the Setting of Vaccination
Hear from Dr. Angela Rasmussen, Virologist, on why serology testing is necessary to help inform a long-term vaccination strategy and confirm vaccine effectiveness
Our Collaboration with the CDC & JRC
Siemens Healthineers collaboration with the Centers for Disease Control and Prevention (CDC) and the Joint Research Centre (JRC) of the European Commission will define a threshold for neutralizing antibody, with the goal of determining the level sufficient to confer immunity.
1Approximately 1 week to 1 month after vaccination.
2Approximately 3, 6, and 9 months and annually; need to boost
3Rodda LB, et al. Functional SARS-CoV-2-specific immune memory persists after mild COVID-19. https://doi.org/10.1101/2020.08.11.20171843. This version posted August 15, 2020.
4Piccoli L, et al. Mapping neutralizing and immunodominant sites on the SARS-CoV-2 spike receptor-binding domain by structure-guided high-resolution serology. Cell. 2020.
5Premkumar, et al. The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients. Sci Immunol. DOI: 10.1126/sciimmunol.abc8413 (2020).
6Wajnberg A, et al. Robust neutralizing antibodies to SARS-CoV-2 infection persist for months. Science. 2020. DOI: 10.1126/science.abd7728.
7Chen X, et al. Disease severity dictates SARS-CoV-2-specific neutralizing antibody responses in COVID-19. Sig Transduct Target Ther. 2020;5:180. https://doi.org/10.1038/s41392-020-00301-9
8Iyer AS, et al. Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV- 2 spike protein in COVID-19 patients. Science Immunology. 2020 Oct 8;5(52):eabe0367. DOI: 10.1126/sciimmunol.abe0367
9Mulligan, MJ et al. Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: InterimReporthttps://www.medrxiv.org/content/10.1101/2020.06.30.20142570v1.full.pdf