ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Several SARS-CoV-2 Omicron subvariants have recently emerged, becoming the dominant circulating strains in many countries. These variants contain a large number of mutations in their Spike glycoprotein, raising concerns about vaccine efficacy. In this study, we evaluate the ability of plasma from a cohort of individuals that received three doses of mRNA vaccine to recognize and neutralize these Omicron subvariant Spikes. We observed that BA.4/5 and BQ.1.1 Spikes are markedly less recognized and neutralized compared to the D614G and the other Omicron subvariant Spikes tested. Also, individuals who have been infected before or after vaccination present better humoral responses than SARS-CoV-2 naive vaccinated individuals, thus indicating that hybrid immunity generates better humoral responses against these subvariants.
ABSTRACT
Continuous emergence of SARS-CoV-2 variants of concern (VOC) is fueling the COVID-19 pandemic. Omicron (B.1.1.529), is rapidly spreading worldwide. The large number of mutations in its Spike raised concerns about a major antigenic drift that could significantly decrease vaccine efficacy and infection-induced immunity. A long interval between BNT162b2 mRNA doses was shown to elicit antibodies that efficiently recognize Spikes from different VOCs. Here we evaluated the recognition of Omicron Spike by plasma from a cohort of SARS-CoV-2 naive and previously-infected individuals that received their BNT162b2 mRNA vaccine 16-weeks apart. Omicron Spike was recognized less efficiently than D614G, Alpha, Beta, Gamma and Delta Spikes. We compared to plasma activity from participants receiving a short (4-weeks) interval regimen. Plasma from individuals of the long interval cohort recognized and neutralized better the Omicron Spike compared to those that received a short interval. Whether this difference confers any clinical benefit against Omicron remains unknown.
ABSTRACT
While the standard regimen of the BNT162b2 mRNA vaccine includes two doses administered three weeks apart, some public health authorities decided to space them, raising concerns about vaccine efficacy. Here, we analyzed longitudinal humoral responses including antibody binding, Fc-mediated effector functions and neutralizing activity against the D614G strain but also variants of concern and SARS-CoV-1 in a cohort of SARS-CoV-2 naive and previously infected individuals, with an interval of sixteen weeks between the two doses. While the administration of a second dose to previously infected individuals did not significantly improve humoral responses, we observed a significant increase of humoral responses in naive individuals after the 16-weeks delayed second shot, achieving similar levels as in previously infected individuals. We compared these responses to those elicited in individuals receiving a short (4-weeks) dose interval. For the naive donors, these responses were superior to those elicited by the short dose interval.
ABSTRACT
IntroductionThe SARS-CoV-2 pandemic has put significant additional pressure on healthcare systems throughout the world. The identification of at-risk population beyond age, pre-existing medical conditions and socioeconomic status has been the subject of only a small part of the global COVID-19 research so far. To this day, more data is required regarding the association between HLA allele and red blood cell (RBC) antigens expression in regard to SARS-CoV-2 infection susceptibility and virus clearance capability, and COVID-19 susceptibility, severity, and duration. MethodsThe phenotypes for ABO and RhD, and the genotypes for 37 RBC antigens and HLA-A, B, C, DRB1, DQB1 and DPB1 were determined using high throughput platforms (Luminex and Next-generation Sequencing) in 90 Caucasian convalescent plasma donors. The results were compared to expected reference frequencies, local and international databases, and literature. ResultsThe AB group was significantly increased (1.5x, p=0.018) and a non-significant (2.2x, p=0.030) increase was observed for the FY*A allele frequency in the convalescent cohort (N=90) compared to reference frequencies. Some HLA alleles were found significantly overrepresented (HLA-B*44:02, C*05:01, DPB1*04:01, DRB1*04:01 and DRB1*07:01) or underrepresented (A*01:01, B51:01 and DPB1*04:02) in convalescent individuals compared to the local bone marrow registry population. ConclusionOur study of infection-susceptible but non-hospitalized Caucasian COVID-19 patients contributes to the global understanding of host genetic factors associated with SARS-CoV-2 infection susceptibility and severity of the associated disease.
ABSTRACT
BackgroundThe SARS-CoV-2 virus is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing more than a million deaths. The SARS-CoV-2 Spike glycoproteins mediate viral entry and represent the main target for antibody responses. Humoral responses were shown to be important for preventing and controlling infection by coronaviruses. A promising approach to reduce the severity of COVID-19 is the transfusion of convalescent plasma. However, longitudinal studies revealed that the level of antibodies targeting the receptor-binding domain (RBD) of the SARS-CoV-2 Spike declines rapidly after the resolution of the infection. Study Design and MethodsTo extend this observation beyond the RBD domain, we performed a longitudinal analysis of the persistence of antibodies targeting the full-length SARS-CoV-2 Spike in the plasma from 15 convalescent donors. We generated a 293T cell line constitutively expressing the SARS-CoV-2 Spike and used it to develop a high-throughput flow cytometry-based assay to detect SARS-CoV-2 Spike specific antibodies in the plasma of convalescent donors. Results and ConclusionWe found that the level of antibodies targeting the full-length SARS-CoV-2 Spike declines gradually after the resolution of the infection. This decline was not related to the number of donations, but strongly correlated with the decline of RBD-specific antibodies and the number of days post-symptom onset. These findings help to better understand the decline of humoral responses against the SARS-CoV-2 Spike and provide important information on when to collect plasma after recovery from active infection for convalescent plasma transfusion.
ABSTRACT
Hema-Quebec, the blood supplier in the Province of Quebec, Canada, collects and tests convalescent plasma used in a clinical trial to determine the clinical efficacy of this product for the treatment of hospitalized COVID-19 patients. So far, we have collected 1159 plasma units from 282 COVID-19 convalescent donors. The presence of antibodies to the receptor binding domain (RBD) of SARS-CoV-2 spike protein in convalescent donors was established at the first donation. Seropositive donors were asked to donate additional plasma units every six days. Until now, 15 donors have donated at least four times and, in some cases, up to nine times. This allowed us to perform a longitudinal analysis of the persistence of SARS-CoV-2 RBD-specific antibodies in these repeat donors, with the first donation occurring 33-77 days after symptoms onset and donations up to 71-114 days after symptoms onset thereafter. In all donors, the level of antibodies remained relatively stable up to about 76 days after symptoms onset but then started to decrease more rapidly to reach, in some convalescent donors, a seronegative status within 100-110 days after symptoms onset. The decline in anti-RBD antibodies was not related to the number of donations but strongly correlated with the numbers of days after symptoms onset (r = 0.821). This suggests that de novo secretion of SARS-CoV-2 RBD antibodies by short-lived plasma cells stopped about 2-3 months after disease onset, an observation that has important implications for convalescent plasma collection and seroprevalence studies undertaken several months after the peak of infection.
ABSTRACT
The SARS-CoV-2 virus is responsible for the current worldwide coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The Spike glycoprotein of SARS-CoV-2 mediates viral entry and is the main target for neutralizing antibodies. Understanding the antibody response directed against SARS-CoV-2 is crucial for the development of vaccine, therapeutic and public health interventions. Here we performed a cross-sectional study on 106 SARS-CoV-2-infected individuals to evaluate humoral responses against the SARS-CoV-2 Spike. The vast majority of infected individuals elicited anti-Spike antibodies within 2 weeks after the onset of symptoms. The levels of receptor-binding domain (RBD)-specific IgG persisted overtime, while the levels of anti-RBD IgM decreased after symptoms resolution. Some of the elicited antibodies cross-reacted with other human coronaviruses in a genus-restrictive manner. While most of individuals developed neutralizing antibodies within the first two weeks of infection, the level of neutralizing activity was significantly decreased over time. Our results highlight the importance of studying the persistence of neutralizing activity upon natural SARS-CoV-2 infection.
