Neutralizing antibody levels against SARS-CoV-2 variants of concern Delta and Omicron in vaccine breakthrough-infected blood donors.

Novel SARS-CoV-2 variants of concern (VOC) Delta and Omicron are able to escape some monoclonal antibody therapies, making again COVID-19 convalescent plasma (CCP) a potential frontline treatment. In this study, we investigated the kinetics of anti-SARS-CoV-2 neutralizing antibodies (nAbs) against VOCs Delta and Omicron in vaccine breakthrough infected plasma donors. Serum samples from 19 donors were collected at the time of plasma donation and tested for anti-SARS-CoV-2 nAbs (using live authentic VOC viral neutralization test) and IgG (Liaison® SARS-CoV-2 S1/S2 and Liaison® SARS-CoV-2 TrimericS IgG assays, DiaSorin). Measures were correlated with different variables, including the time between last vaccine dose and CCP donation, and time between SARS-COV-2 infection and CCP donation. nAb titers against VOC Delta and Omicron were directly related to the time interval since last vaccine dose to CCP donation, but inversely related to time since COVID19 breakthrough infection. SARS-CoV-2 breakthrough infection in vaccinated in donors boosts nAb titers against VOCs Delta and Omicron, but such titers decay shortly after infection. Therefore, CCP must be collected early after vaccine breakthrough infection.

Franchini M ，Focosi D ，Mengoli C ，Percivalle E ，Sammartino JC ，Ferrari A ，Zani M ，Glingani C ，Baldanti F ... -  《-》

Pre-Omicron Vaccine Breakthrough Infection Induces Superior Cross-Neutralization against SARS-CoV-2 Omicron BA.1 Compared to Infection Alone.

da Silva ES ，Kohnen M ，Gilson G ，Staub T ，Arendt V ，Hilger C ，Servais JY ，Charpentier E ，Domingues O ，Snoeck CJ ，Ollert M ，Seguin-Devaux C ，Perez-Bercoff D ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Convalescent plasma donors show enhanced cross-reactive neutralizing antibody response to antigenic variants of SARS-CoV-2 following immunization.

The therapeutic benefit of convalescent plasma (CP) therapy to treat COVID-19 may derive from neutralizing antibodies (nAbs) to SARS-CoV-2. To investigate the effects of antigenic variation on neutralization potency of CP, we compared nAb titers against prototype and recently emerging strains of SARS-CoV-2, including Delta and Omicron, in CP donors previously infected with SARS-CoV-2 before and after immunization. Samples were assayed from previously SARS-CoV-2 infected donors before (n = 17) and after one (n = 43) or two (n = 71) doses of Astra-Zeneca or Pfizer vaccinations. Ab titers against Wuhan/wild type (WT), Alpha, Beta, and Delta SARS-CoV-2 strains were determined by live virus microneutralization assay while titers to Omicron used a focus reduction neutralization test. Anti-spike antibody was assayed by Elecsys anti-SARS-CoV-2 quantitative spike assay (Roche). Unvaccinated donors showed a geometric mean titer (GMT) of 148 against WT, 80 against Alpha but mostly failed to neutralize Beta, Delta, and Omicron strains. Contrastingly, high GMTs were observed in vaccinated donors against all SARS-CoV-2 strains after one vaccine dose (WT:703; Alpha:692; Beta:187; Delta:215; Omicron:434). By ROC analysis, reactivity in the Roche quantitative Elecsys spike assay of 20,000 U/mL was highly predictive of donations with nAb titers of ≥1:640 against Delta (90% sensitivity; 97% specificity) and ≥1:320 against Omicron (89% sensitivity; 81% specificity). Vaccination of previously infected CP donors induced high levels of broadly neutralizing antibodies against circulating antigenic variants of SARS-CoV-2. High titer donations could be reliably identified by automated quantitative anti-spike antibody assay, enabling large-scale preselection of high-titer convalescent plasma.

Harvala H ，Nguyen D ，Simmonds P ，Lamikanra AA ，Tsang HP ，Otter A ，Maes P ，Webster M ，Clarkson A ，Kaloyirou F ，Hopkins V ，Laidlaw SM ，Carroll M ，Mora A ，Griffiths A ，MacLennan S ，Estcourt L ，Roberts DJ ... -  《-》

Immunogenicity of convalescent and vaccinated sera against clinical isolates of ancestral SARS-CoV-2, Beta, Delta, and Omicron variants.

SARS-CoV-2 Omicron variant of concern (VOC) has evolved multiple mutations within the spike protein, raising concerns of increased antibody evasion. In this study, we assessed the neutralization potential of COVID-19 convalescent sera and sera from vaccinated individuals against ancestral SARS-CoV-2 and VOCs. The neutralizing activity of sera from 65 coronavirus disease (COVID-19) vaccine recipients and convalescent individuals against clinical isolates of ancestral SARS-CoV-2 and Beta, Delta, and Omicron VOCs was assessed using a micro-neutralization assay. Convalescent sera from unvaccinated individuals infected by the ancestral virus demonstrated reduced neutralization against Beta and Omicron VOCs. Sera from individuals that received three doses of the Pfizer or Moderna vaccines demonstrated reduced neutralization of the Omicron variant relative to ancestral SARS-CoV-2. Sera from individuals that were naturally infected with ancestral SARS-CoV-2 and subsequently received two doses of the Pfizer vaccine induced significantly higher neutralizing antibody levels against ancestral virus and all VOCs. Infection alone, either with ancestral SARS-CoV-2 or the Delta variant, was not sufficient to induce high neutralizing antibody titers against Omicron. In summary, we demonstrate that convalescent and vaccinated sera display varying levels of SARS-CoV-2 VOC neutralization. Data from this study will inform booster vaccination strategies against SARS-CoV-2 VOCs. This research was funded by the Canadian Institutes of Health Research (CIHR). VIDO receives operational funding from the Government of Saskatchewan through Innovation Saskatchewan and the Ministry of Agriculture and from the Canada Foundation for Innovation through the Major Science Initiatives for its CL3 facility.

Banerjee A ，Lew J ，Kroeker A ，Baid K ，Aftanas P ，Nirmalarajah K ，Maguire F ，Kozak R ，McDonald R ，Lang A ，Gerdts V ，Straus SE ，Gilbert L ，Li AX ，Mozafarihashjin M ，Walmsley S ，Gingras AC ，Wrana JL ，Mazzulli T ，Colwill K ，McGeer AJ ，Mubareka S ，Falzarano D ... -  《Med-US》

Simple prediction of COVID-19 convalescent plasma units with high levels of neutralization antibodies.

Hyperimmune convalescent COVID-19 plasma (CCP) containing anti-SARS-CoV-2 neutralizing antibodies (NAbs) was proposed as a therapeutic option for patients early in the new coronavirus disease pandemic. The efficacy of this therapy depends on the quantity of neutralizing antibodies (NAbs) in the CCP units, with titers ≥ 1:160 being recommended. The standard neutralizing tests (NTs) used for determining appropriate CCP donors are technically demanding and expensive and take several days. We explored whether they could be replaced by high-throughput serology tests and a set of available clinical data. Our study included 1302 CCP donors after PCR-confirmed COVID-19 infection. To predict donors with high NAb titers, we built four (4) multiple logistic regression models evaluating the relationships of demographic data, COVID-19 symptoms, results of various serological testing, the period between disease and donation, and COVID-19 vaccination status. The analysis of the four models showed that the chemiluminescent microparticle assay (CMIA) for the quantitative determination of IgG Abs to the RBD of the S1 subunit of the SARS-CoV-2 spike protein was enough to predict the CCP units with a high NAb titer. CCP donors with respective results > 850 BAU/ml SARS-CoV-2 IgG had a high probability of attaining sufficient NAb titers. Including additional variables such as donor demographics, clinical symptoms, or time of donation into a particular predictive model did not significantly increase its sensitivity and specificity. A simple quantitative serological determination of anti-SARS-CoV-2 antibodies alone is satisfactory for recruiting CCP donors with high titer NAbs.

Jazbec K ，Jež M ，Žiberna K ，Mali P ，Ramšak Ž ，Potokar UR ，Kvrzić Z ，Černilec M ，Gracar M ，Šprohar M ，Jovanovič P ，Vuletić S ，Rožman P ... -  《Virology Journal》