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The Omicron BQ.1.1 variant is now the major SARS-CoV-2 circulating strain in many countries. Because of the many mutations present in its Spike glycoprotein, this variant is resistant to humoral responses elicited by monovalent mRNA vaccines. With the goal to improve immune responses against Omicron subvariants, bivalent mRNA vaccines have recently been approved in several countries. In this study, we measure the capacity of plasma from vaccinated individuals, before and after a fourth dose of mono- or bivalent mRNA vaccine, to recognize and neutralize the ancestral (D614G) and the BQ.1.1 Spikes. Before and after the fourth dose, we observe a significantly better recognition and neutralization of the ancestral Spike. We also observe that fourth-dose vaccinated individuals who have been recently infected recognize and neutralize better the BQ.1.1 Spike, independently of the mRNA vaccine used, than donors who have never been infected or have an older infection. Our study supports that hybrid immunity, generated by vaccination and a recent infection, induces higher humoral responses than vaccination alone, independently of the mRNA vaccine used.
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PurposeLong-term humoral immunity to COVID-19 is not well understood owing to the continuous emergence of new variants of concern, the evolving vaccine- and infection-induced immunity, and the limited follow-up of previous studies. As the blood service in Quebec (Canada), we established in April 2021 a COVID-19-focused biobank. ParticipantsAs of January 2022, included 86,229 plasma samples from 15,502 regular donors (age range=18-84 years, female %=49.7%), for an average of 5.6 donations per donor. Nearly two thirds (65.6%) of biobank donors made at least 2 donations, with many donors having provided samples pre- and post-vaccination (3061 [19.75%]) or pre- and post-infection (131 [0.85%]), thus allowing longitudinal studies on vaccine- and infection-induced immunity. Findings to dateComparative analysis of the immune response after the first and second dose of the BNT162b2 COVID-19 vaccine among SARS-CoV-2 naive and previously infected individuals revealed that a single vaccine dose administered to previously infected individuals yields a maximal immune response. In contrast, SARS-CoV-2 naive individuals required two vaccine doses to produce a maximal immune response. Furthermore, the results of a four-phase seroprevalence study indicate that the anti-N antibody response wanes quite rapidly, so that up to one third of previously infected donors were seronegative for anti-N. Future plansThis plasma biobank from frequent and motivated donors, and the longitudinal nature of the biobank, will provide valuable insights into the anti-SARS-CoV-2 immune response and its persistence in time, and the effect of vaccination and of viral variants on the specificity of the antiSARS-CoV-2 immune response. Strengths and LimitationsThe herein described biobank has several strengths. To the best of our knowledge, this would be the largest biobank of plasma samples dedicated to COVID-19 research, with >80,000 samples from >15,000 donors and new samples continually being added until at least December 2022. Furthermore, the large subset of donors with [≥]2 samples (65.6%) - along with the high frequency of donations in this subset (i.e., median: once every 29.0 days) - enables the conduct of longitudinal analyses on COVID-19 immunity. Another strength is that donors provided a broad consent, which allows researchers to recontact them for other projects (e.g., supplemental questionnaire). Lastly, the cost of establishing the biobank was minimized since the infrastructure and personnel required for sample collection were already in place at our blood collection sites. Given these strengths, our biobank may serve as a model for other blood operators and government partners who would be interested in reproducing our initiative elsewhere. Certain limitations should nonetheless be considered when using our biobank samples. First, only plasma samples are available, such that the biobank cannot be used to study cell-based immunity. Researchers interested in studying cell-based immunity may want to contact BCQ19, which routinely collects peripheral blood mononuclear cells.[1] Second, despite the large sample, the plasma donor population is not fully representative of the overall Quebec population, as expected since plasma donors are typically more representative of the healthy adult population. All exclusion criteria for plasma donations were also exclusion criteria for the biobank including immunodeficiencies, active infection, recent cancer among other chronic diseases. Third, the database associated with our biobank does not include information on disease severity, such as hospitalization or intensive care unit admission. Fourth, the database does not include information on socioeconomic status, such as income and education. However, the six-digit zip code can be used to generate a proxy index for socioeconomic status.
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BackgroundEmerging evidence suggests that COVID-19 vaccination decreases the sensitivity of anti-nucleocapsid (N) serologies, making them less reliable to assess recently-acquired infections. We therefore developed and tested a new approach based on the ratio of the anti-N absorbance of longitudinal samples to overcome this limitation. MethodsPreviously vaccinated repeat plasma donors provided at least one pre-infection (reference) and one post-infection (test) sample. All samples were tested using an in-house anti-N ELISA. Seropositivity was determined based on the ratio between the anti-N absorbance of the test and reference samples. The ratio approach was tested in a real-world setting during three cross-sectional serosurveys carried out among plasma donors in Quebec, Canada. ResultsUsing a cut-off ratio of 1.5, the approach had a sensitivity of 95.2% among the 248 previously vaccinated and infected donors compared with 63.3% for the conventional approach. When tested in a real-world setting, the ratio-based approach yielded an adjusted seroprevalence of 27.4% (95% confidence interval [CI]=23.8%-30.9%) at the latest time point considered, compared to 15.1% (95% CI=12.2%-18.0%) for the conventional approach. ConclusionsThis article describes a new and highly-sensitive approach that captures a significantly greater proportion of vaccinated individuals with a recent history of SARS-CoV-2 infection.
