SARS-CoV-2 Virus-Like Particle Neutralizing Capacity in Blood Donors Depends on Serological Profile and Donor-Declared SARS-CoV-2 Vaccination History

Abstract

In the first 3 months of 2021 as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination was in the initial stages of a mass rollout, Canadian blood donors had various levels of humoral protection against wild-type and variant of concern (VOC) SARS-CoV-2. Very few Canadians would have received a second dose of a SARS-CoV-2 vaccine.

Utilization of the Abbott SARS-CoV-2 IgG II Quant Assay To Identify High-Titer Anti-SARS-CoV-2 Neutralizing Plasma against Wild-Type and Variant SARS-CoV-2 Viruses

“…There were also recommendations against the use of CCP for treating COVID-19 in “hospitalized patients without impaired humoral immunity” ( 1 ). Our group at Canadian Blood Services previously was focused on supporting CCP studies in Canada ( 2 – 5 ), and this led us to initiate a “correlates of immunity” project, which had the stated goal of understanding changes in anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) neutralizing capacity as the COVD-19 pandemic advanced and identifying methods to identify and characterize high-titer donor plasma ( 2 , 3 , 6 , 7 ). During this preliminary work, we validated 50% plaque reduction/neutralization titer (PRNT 50 ) assays using binding antibody, competitive binding assays, and virus-like particle (VLP) assays for wild-type SARS-CoV-2 ( 3 ).…”

“…Given the labor-intensive nature of PRNT 50 testing, we also noted a requirement for a laboratory-based rapid screening assay to identify high-titer CCP and to decrease overall tests costs per unit of qualified CCP. We also later determined that the neutralizing capacity of donor plasma could vary between wild-type and emerging variants of concern (VOCs) ( 7 ). The rationale to use CCP in early stage COVID-19 is further supported in the study that SARS-CoV-2 virus can only be cultured from early stage COVID-19 patients ( 11 ).…”

A Qualitative Comparison of the Abbott SARS-CoV-2 IgG II Quant Assay against Commonly Used Canadian SARS-CoV-2 Enzyme Immunoassays in Blood Donor Retention Specimens, April 2020 to March 2021

“…Assays that bridge between qualitative binding and quantitative neutralization are important, and this study focused on the qualitative binding element of immunity. In our previous studies, we have shown a difference in detection of binding versus neutralizing anti-SARS-CoV-2 antibodies in specimens from the same cohort of blood donors in our Correlates of Immunity project ( 9 , 10 ). Other work has shown that not all binding antibodies correlate to neutralization but that IgG against RBD (and to a lesser extent, S) can act as an indicator of neutralization ( 2 , 42 ).…”

“…The identification of waning neutralizing antibody responses in blood donors ( 1 ) led to the development of a further “Correlates of Immunity” project, which had the stated goal of understanding changes in anti-SARS-CoV-2-neutralizing capacity as the COVID-19 pandemic advanced. As part of this Correlates of Immunity project, our group was able to sample 1,500 retention specimens a month from Canadian blood donors using a repeated cross-sectional design with random cross-sectional sampling of all available retention samples for a 12-month period from April 2020 until March 2021 ( 6 – 10 ). During this process, we used a variety of assays that have been widely used by our and other groups to assess SARS-CoV-2 seroprevalence in Canada.…”

“…Given the absence of a gold standard ( 6 , 21 ), we previously characterized SARS-CoV-2 seropositivity, including latent class analysis ( 7 , 8 ) and composite reference standard approaches ( 6 ). We also attempted to understand the impact of donor-declared vaccine history on SARS-CoV-2 serological profiles ( 1 , 2 , 9 , 10 ). We have noted that responses of different assays are, at times, inconsistent with one another ( 1 , 6 – 9 ).…”