Diminished Neutralization Capacity of SARS-CoV-2 Omicron BA.1 in Donor Plasma Collected from January to March 2021

ABSTRACT The 50% plaque reduction neutralization assay (PRNT 50 ) has been previously used to assess the neutralization capacity of donor plasma against wild-type and variant of concern (VOC) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging data suggest that plasma with an anti-SARS-CoV-2 level of ≥2 × 10 4 binding antibody units/mL (BAU/mL) protects against SARS-CoV-2 Omicron BA.1 infection. Specimens were collected using a cross-sectional random sampling approach. For PRNT 50 studies, 63 previously analyzed specimens by PRNT 50 versus SARS-CoV-2 wild-type, Alpha, Beta, Gamma, and Delta were analyzed by PRNT 50 versus Omicron BA.1. The 63 specimens plus 4,390 specimens (randomly sampled regardless of serological evidence of infection) were also tested using the Abbott SARS-CoV-2 IgG II Quant assay (anti-spike [S]; Abbott, Chicago, IL, USA; Abbott Quant assay). In the vaccinated group, the percentages of specimens with any measurable PRNT 50 versus wild-type or VOC were wild type (21/25 [84%]), Alpha (19/25 [76%]), Beta (18/25 [72%]), Gamma (13/25 [52%]), Delta (19/25 [76%]), and Omicron BA.1 (9/25 [36%]). In the unvaccinated group, the percentages of specimens with any measurable PRNT 50 versus wild type or VOC were wild-type SARS-CoV-2 (16/39 [41%]), Alpha (16/39 [41%]), Beta (10/39 [26%]), Gamma (9/39 [23%]), Delta (16/39 [41%]), and Omicron BA.1 (0/39) (Fisher’s exact tests, vaccinated versus unvaccinated for each variant, P < 0.05). None of the 4,453 specimens tested by the Abbott Quant assay had a binding capacity of ≥2 × 10 4 BAU/mL. Vaccinated donors were more likely than unvaccinated donors to neutralize Omicron when assessed by a PRNT 50 assay. IMPORTANCE SARS-CoV-2 Omicron emergence occurred in Canada during the period from November 2021 to January 2022. This study assessed the ability of donor plasma collected earlier (January to March 2021) to generate any neutralizing capacity against Omicron BA.1 SARS-CoV-2. Vaccinated individuals, regardless of infection status, were more likely to neutralize Omicron BA.1 than unvaccinated individuals. This study then used a semiquantitative binding antibody assay to screen a larger number of specimens (4,453) for individual specimens that might have high-titer neutralizing capacity against Omicron BA.1. None of the 4,453 specimens tested by the semiquantitative SARS-CoV-2 assay had a binding capacity suggestive of a high-titer neutralizing capacity against Omicron BA.1. These data do not imply that Canadians lacked immunity to Omicron BA.1 during the study period. Immunity to SARS-CoV-2 is complex, and there is still no wide consensus on correlation of protection to SARS-CoV-2.