key: cord-0262734-w17kfbg7 authors: Bassi, J.; Giannini, O.; Silacci-Fregni, C.; Pertusini, L.; Hitz, P.; Terrot, T.; Franzosi, Y.; Muoio, F.; Saliba, C.; Meury, M.; Dellota, E.; Dillen, J.; Hernandez, P.; Czudnochowski, N.; Cameroni, E.; Beria, N.; Ventresca, M.; Badellino, A.; Lavorato-Hadjeres, S.; Lecchi, E.; Bonora, T.; Mattiolo, M.; Trinci, G.; Garzoni, D.; Bonforte, G.; Forni-Ogna, V.; Giunzioni, D.; Berwert, L.; Gupta, R. K.; Ferrari, P.; Ceschi, A.; Cippa', P.; Corti, D.; Lanzavecchia, A.; Piccoli, L. title: Defective neutralizing antibody response to SARS-CoV-2 in vaccinated dialysis patients date: 2021-10-07 journal: nan DOI: 10.1101/2021.10.05.21264054 sha: ba8ac68f6cc9397030645bd96f10402e157b80cb doc_id: 262734 cord_uid: w17kfbg7 Patients on dialysis are at risk of severe course of SARS-CoV-2 infection. Understanding the neutralizing activity and coverage of SARS-CoV-2 variants of vaccine-elicited antibodies is required to guide prophylactic and therapeutic COVID-19 interventions in this frail population. By analyzing plasma samples from 130 hemodialysis (HD) and 13 peritoneal dialysis patients after two doses of BNT162b2 or mRNA-1273 vaccines, we found that 35% of the patients had low-level or undetectable IgG antibodies to SARS-CoV-2 Spike (S). Neutralizing antibodies against the vaccine-matched SARS-CoV-2 and Delta variant were low or undetectable in 49% and 77% of patients, respectively, and were further reduced against other emerging variants. The fraction of non-responding patients was higher in SARS-CoV-2-naive HD patients immunized with BNT162b2 (66%) than those immunized with mRNA-1273 (23%). The reduced neutralizing activity correlated with low antibody avidity, consistent with a delayed affinity maturation of SARS-CoV-2 S-specific B cells. These data indicate that dialysis patients should be considered for an additional boost and other therapeutic strategies, including early immunotherapy with monoclonal antibodies. Patients with chronic kidney disease (CKD), in particular those with end-stage kidney disease (ESKD) on dialysis, are highly predisposed to infections, which are the major cause of morbidity and the second cause of mortality in this vulnerable population 1,2 . Infection by SARS-CoV-2, the causative agent of the Coronavirus disease-2019 (COVID-19), has posed a new threat for CKD patients, who were found to have a greater risk of severe COVID-19 course 3,4 . Early reports indicated a case fatality ranging from 10 to 30% in patients on hemodialysis 5-10 . The rapid development of COVID-19 vaccines has provided an important strategy to prevent SARS-CoV-2 infection and, especially, severe COVID-19 course. In particular, mRNA-based vaccines developed by Pfizer/BioNTech (BNT-162b2) and Moderna (mRNA-1273) have demonstrated high safety and efficacy in healthy and at-risk individuals, including patients with chronic diseases, cancer and solid organ transplantation [11] [12] [13] [14] . However, immunosuppressed patients, in particular those with hematological malignancies, autoimmune diseases and solid organ transplantations, were shown to mount a low antibody response to these vaccines [15] [16] [17] [18] [19] [20] . Because of their immunological frailty, patients on dialysis were prioritized in international COVID-19 vaccination programs 21 . Recent studies in HD patients showed a delayed and lower serological response to vaccines and a rapid decline of anti-SARS-CoV-2 antibodies 19,22-24 . These findings suggest an overall diminished vaccine response to SARS-CoV-2 in ESKD patients that is reminiscent of the low response observed after vaccination against Hepatitis B virus (HBV) and seasonal Influenza virus 25, 26 . In addition, the rapid increase At this stage of the pandemic, it is urgent to identify populations not developing sufficient levels of neutralizing antibodies against circulating SARS-CoV-2 variants, which therefore may be at-risk of developing severe COVID-19. In this study, we provide evidence of the defective neutralizing antibody response to mRNA-vaccines in the dialysis population, which supports the strategy of prioritizing these patients for an additional boost and other therapeutic strategies. Blood samples were obtained from 143 dialysis patients and 48 healthcare workers under study protocols approved by the local Institutional Review Boards (Canton Ticino Ethics Committee, Switzerland). Dialysis patients and HCW were recruited from the four public hospitals of the Ente Ospedaliero Cantonale (EOC) in Ticino (Southern Switzerland). All subjects provided written informed consent for the use of blood and blood components (such as PBMCs, sera or plasma). Blood samples were collected before and 2-3 weeks after the first and the second COVID-19 vaccine dose. Plasma was isolated from blood draw performed using BD tubes containing Ficoll (BD, CPT Ficoll, Cat. No. 362780) and stored at +4°C until use. Cell lines used in this study were obtained from ATCC (Vero E6 TMPRSS2) or ThermoFisher Scientific (Expi CHO cells, Expi293F™ and FreeStyle 293 cells). Vero E6 TMPRSS2 cells . CC-BY-NC-ND 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 7, 2021. ; https://doi.org/10.1101/2021. 10 .05.21264054 doi: medRxiv preprint were grown in DMEM supplemented with 10% HyClone (FBS). Expi293F cells were grown in Expi Medium. The SARS-CoV-2 RBD WT construct was synthesized by GenScript into phCMV1, with a sequence encoding an N-terminal mu-phosphatase signal peptide, an 'ETGT' linker, SARS-CoV-2 S residues 328-531, a linker sequence, an Avi tag, a twin Strep tag and a 8xHis-tag. Recombinant ACE2 (UniProt Q9BYF1, residues 19-615 with a C-terminal thrombin cleavage site-TwinStrep-10xHis-GGG-tag, and N-terminal signal peptide) and RBD WT constructs were transiently transfected into Expi293F cells following manufacturer's instructions as previously describedSupernatants were clarified by centrifugation and affinity purified using a 5 mL StrepTrap column VWR) . The SARS-CoV-2 stabilized Spike WT (D614G) construct was synthesized by GenScript into pCDNA with an N-terminal mu-phosphatase signal peptide, 2P stabilizing mutation 28, 29 , a TEV cleavage site and a C-terminal foldon, 8x His-tag, Avi tag and C-tag 30 and expressed in FreeStyle 293 cells following manufacturer's instructions. Supernatants were clarified by centrifugation and affinity purified using a 5 mL C-tag affinity matrix column. Amino acid substitutions were introduced into the D614G pCDNA_SARS-CoV-2_S plasmid as previously described 31 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 7, 2021. ; https://doi.org/10.1101/2021.10.05.21264054 doi: medRxiv preprint Replication defective VSV pseudovirus 33 expressing SARS-CoV-2 Spike proteins corresponding to the different VOC were generated as previously described 34 . Vero E6-TMPRSS2 were grown in DMEM supplemented with 10% FBS and seeded into white bottom 96 well plates (PerkinElmer, 6005688), as previously described 35 Spectraplate-384 with high protein binding treatment (custom made from Perkin Elmer) were coated overnight at 4°C with 5 µg/mL RBD or 1 µg/mL SARS-CoV-2 S protein in PBS. The day after plates were washed and blocked with Blocker Casein in PBS (Thermo Fisher Scientific, 37528) supplemented with 0.05% Tween 20 (Sigma Aldrich), 1h RT. Serial dilutions of plasma samples were then added to plates for 1h RT. Alkaline Phosphataseconjugated goat anti-human IgG, IgM or IgA (Southern Biotech) were added to plates and incubated for 1h RT. 4-NitroPhenyl Phosphate (pNPP, Sigma-Aldrich, N2765-100TAB) . CC-BY-NC-ND 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint Avidity Index was calculated as the ratio (%) of the ED50 in presence and the ED50 in absence of NaSCN. Plasma were diluted in PBS and mixed with SARS-CoV-2 RBD mouse Fc-tagged antigen (Sino Biological, 40592-V05H, final concentration 20 ng/ml) and incubated for 30 min at 37°C. The percentage of inhibition was calculated as follows: (1−(OD sample−OD neg ctr)/(OD pos ctr−OD neg ctr)]) × 100. The study was designed to have 80% power to detect a minimum 25% difference in total incidence of cases with poor neutralizing antibody response (i.e., low or undetectable plasma antibody titers) or in average neutralizing titers between dialysis patients and healthy controls as well as within the HD subgroups. Comparisons of means between two groups of unpaired data were made with Mann-Whitney rank test. Comparisons of means between multiple groups of unpaired data were made with Kruskal-Wallis rank test and corrected with Dunn's test. Comparisons of means between multiple groups of matched data were made with Friedman rank test and corrected with Dunn's test. Relative risks of defective neutralizing response in selected groups of patients were calculated from 2x2 contingency tables using two-sided Fisher's exact test. Statistical significance is set as P<0.05 and P-values are indicated with: ns = non-significant; *=0.033; **=0.002; ***<0.001. ED50 and ID50 titers were calculated from . CC-BY-NC-ND 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 7, 2021. ; https://doi.org/10.1101/2021.10.05.21264054 doi: medRxiv preprint the interpolated value from the log(agonist) and the log(inhibitor), respectively, versus response, using variable slope (four parameters) non-linear regression. Data were plotted and analyzed with GraphPad Prism software (version 9.1.0). Table 1 . Of note, twenty-four (17%) dialysis patients were previously infected with SARS-CoV-2, of whom 18 (75%) had severe COVID-19 requiring hospitalization (13) or admission to an intensive care unit (5). A group of 48 healthcare workers, who received two doses of BNT162b2 vaccine between April and June 2021, were included as healthy controls (HC). Twenty-four HC were previously infected with SARS-CoV-2 reporting mild symptoms that did not require hospitalization. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 7, 2021. ; https://doi.org/10.1101/2021.10.05.21264054 doi: medRxiv preprint infected with SARS-CoV-2, and moderate to high levels in 29.2% of HD and 79.2% of HC, who had not been exposed to the virus (Supplementary Figure S1) . Importantly, although anti-SARS-CoV-2 S antibodies were measured in 94.4% of dialysis patients after the second vaccine dose, 35% of them had still low or undetectable levels of antibodies, compared to 100% of HC showing high levels of S-specific IgG (Figure 1a-b) . The larger fraction of donors with low or no antibodies (36.9%) was represented by the HD group, with naïve patients immunized with BNT162b2 showing the lowest levels of plasma IgG (50.6%) compared to those who received mRNA-1273 (9.1%) (Figure 1a-b) . The lower IgG level in naïve HD patients was the result of a slower kinetics of antibodies induced by the vaccines as compared to naïve HC and previously infected donors (Figure 1c ). Of note, average antibody titers of previously infected HD patients were higher than those of HC (Figure 1a) , a finding that is consistent with more severe COVID-19 course in these patients [36] [37] [38] . Plasma samples from the 13 PD patients were collected only after the second vaccine dose and all the donors showed detectable S-specific IgG with average plasma levels that were comparable to those of HC (Figure 1a-b) . S-specific IgG levels highly correlated with RBDspecific IgG, suggesting that, similarly to natural infection, antibodies to this domain is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 7, 2021. ; https://doi.org/10.1101/2021.10.05.21264054 doi: medRxiv preprint To determine the neutralizing activity of vaccine-induced antibodies, we performed an in vitro neutralization assay of plasma samples using pseudotyped vesicular stomatitis virus (VSV) that express the Wuhan wild-type (WT, D614) SARS-CoV-2 S glycoprotein ( Figure 2a and Supplementary Figure S3a ). Compared to HC, 49% of dialysis patients had no or low neutralizing activity against the vaccine-matched SARS-CoV-2 strain (Figure 2b ). In particular, while most of previously infected HD patients (87%) had moderate to high neutralizing antibody titers, which were similar or higher than those of HC, naïve HD patients had a heterogenous response with 57.0% of them characterized by a poor neutralizing activity, which was completely absent in the majority (60.7%) of these patients (Figure 2a) . Of note, the fraction of non-responding patients was higher in naïve HD patients immunized with BNT162b2 (65.9%) than those immunized with mRNA-1273 (22.7%) (Figure 2b) . Despite higher plasma S-specific IgG titers (Figure 1a-b) , 60% of naïve PD patients had a similar poor neutralizing response compared to naïve HD patients, with 33.3% of those, who received BNT162b2 vaccine, showing no neutralizing activity (Figure 2a-b) . The poor neutralizing activity was confirmed also by the low capability of plasma antibodies to inhibit binding of RBD to human ACE2 receptor (Supplementary Figure S3b) . Interestingly, in previously infected dialysis patients, we observed average neutralizing and ACE2-inhibiting antibody titers that were higher than those of HC and correlated with S-and RBD-specific IgG levels We next performed a sub-analysis to understand which socio-demographic and clinical data were associated to a significant risk for dialysis patients of being poor responders, here defined as having low or no neutralizing antibody titers after two mRNA-vaccine doses. Among all patients, dialysis mode (HD or PD) was not identified as risk factor, whereas . CC-BY-NC-ND 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 7, 2021. vaccination with BNT162b2 and no previous SARS-CoV-2 infection represented the major risk factors for having a defective neutralizing antibody response (relative risk of 2.75 and 4.50, respectively) ( Table 2) . Within the larger HD group, socio-demographic factors, including gender, age, body mass index, smoke and dialysis features could not be identified as risk factors (Table 3) . Among comorbidities, we found that patients with heart failure history had an 1.68increased relative risk of poor response. As expected, patients in therapy with immunosuppressive drugs had a 1.53 relative risk of poor response to the vaccine with, in particular, calcineurin inhibitors accounting for the highest relative risk (1.87). Vaccination with BNT162b2 was confirmed as a major factor with a relative risk of poor response of 2.88, which increased to 3.60 in 22 naïve HD patients who were matched to 22 naïve HD patients immunized with mRNA-1273 by age, gender, dialysis vintage and comorbidities. Among HD patients immunized with BNT162b2, those older than 80 and with heart failure history had an increased risk of poor response of 1.57 and 1.55, respectively (Table 3) . Collectively, these findings suggest that frailer and/or immunosuppressed naïve dialysis patients are at risk of failing to produce sufficient levels of SARS-CoV-2 neutralizing antibodies after vaccination with BNT162b2. We next addressed the question whether vaccine-induced antibodies that neutralize wild-type SARS-CoV-2 could also neutralize current circulating SARS-CoV-2 variants, in is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 7, 2021. Figure S4a) . Collectively, these findings show that the reduced neutralizing activity of vaccine-elicited antibodies against wild-type SARS-CoV-2 in dialysis patients is further affected against other circulating variants. To explain the defective neutralizing activity of vaccine-induced antibodies observed in dialysis patients, we hypothesized that these antibodies did not gain a sufficient avidity to bind and neutralize SARS-CoV-2 after two vaccine doses. We therefore determined the avidity of plasma antibodies by measuring their binding to SARS-CoV-2 S in presence of sodium thiocyanate, a chaotropic agent that induces dissociation of the antibody from the antigen in case of low affinity. While most of the previously infected HD patients (87%) showed moderate . CC-BY-NC-ND 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 7, 2021. ; https://doi.org/10.1101/2021.10.05.21264054 doi: medRxiv preprint to high-avidity antibodies, a high fraction of naïve HD showed low-(42%) or no (9%) avidity antibodies and most of the naïve PD patients (75%) also showed low-avidity antibodies ( Figure 3a ). As expected, antibodies of all HC that were previously infected with SARS-CoV-2 showed high avidity (index >50%), whereas naïve HC showed moderate avidity (23-50%), consistent with the different duration of affinity maturation ongoing in the two groups (Figure 3a) . The avidity indexes correlated with SARS-CoV-2 S-specific antibody and neutralizing titers (Figure 3b and Supplementary Figure S5a) . In particular, we observed larger fractions of HD patients with moderate to high avidity among patients with higher neutralizing antibody titers (Figure 3c) . The lower avidity titers were paralleled by higher fractions of dialysis patients showing low-or non-neutralizing antibodies against the Delta and other SARS-CoV-2 variants (Figure 3d and Supplementary Figure S5b-f) . Collectively, these data support the hypothesis that vaccine-induced antibodies require high avidity to neutralize SARS-CoV-2 and different variants. In this phase of the COVID-19 pandemic where SARS-CoV-2 variants are rapidly spreading worldwide, we urgently need to understand the efficacy of vaccines administered so far in high-risk immunocompromised populations, in particular patients with chronic diseases 39, 40 . In this study, we provide evidence that dialysis patients do not develop sufficient is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 7, 2021. ; https://doi.org/10.1101/2021.10.05.21264054 doi: medRxiv preprint first and the second dose in HD patients who were naïve to SARS-CoV-2, a finding consistent with a delayed immune response in this population 19, 43, 44 . These data suggest that measuring serum antibody titers to SARS-CoV-2 in dialysis patients could help clinicians to identify vaccine non-responders and guide clinical decision-making. However, currently available serological tests detect antibodies against the Spike of the Wuhan SARS-CoV-2 and do not define the level of neutralizing activity against the virus, which is considered a more relevant serological correlate of protection 45 . In this study, we found that 49% of dialysis patients had low or undetectable levels of neutralizing antibodies against the vaccine-matched SARS-CoV-2 with a significant reduction in neutralizing titers against different circulating SARS-CoV-2 variants in dialysis patients, which is consistent with an immune evasion by the virus 27, 35 . Based on these data, we calculated that the fraction of dialysis patients non-responding to the vaccine further increased to 77% in the case of the Delta variant, suggesting that the great majority of dialysis patient immunized with two doses of an mRNA vaccine may not develop a protective antibody response against SARS-CoV-2 variants. Despite the huge discrepancy between the fraction of non-responders based on antibody levels and on neutralizing titers, we observed a high correlation between these titers, which may help to define proper cut-offs in the serological tests used in clinical settings to identify non-responding patients. Furthermore, the correlation observed between neutralizing activity and antibody avidity suggests that the identification of non-responding patients may be helped by a SARS-CoV-2 avidity test, as successfully implemented for other infectious diseases 46-50 . We identified that having never been exposed to SARS-CoV-2 is the major factor that increases the risk of a defective antibody response after vaccination, especially in HD patients. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint 51 . This effect can be explained by the higher antibody avidity that previously infected patients gained over time compared to naïve patients, who instead showed a delayed and low-avidity response. These findings are consistent with a slower affinity maturation of SARS-CoV-2 S-specific B cells, which appears to be a peculiar immunological feature of the dialysis population. A recent report by Carr et al 52 , showed that naïve HD patients vaccinated with BNT162b2 developed higher neutralizing antibodies against SARS-CoV-2 variants compared to Astra Zeneca -Oxford University AZD1222 vaccine, suggesting that mRNA vaccines provide a higher level of protection in dialysis patients compared to adenovirus-based vaccines. However, a difference in efficacy may exist among mRNA vaccines, as we found that being immunized with BNT162b2 instead of mRNA-1273 was the second most relevant risk factor for a defective response in the dialysis population, especially in naïve HD patients. This difference can be explained by the lower mRNA amount provided by one dose of BNT162b2 compared to mRNA-1273 11, 12 . Indeed, the mRNA-1273 vaccine was found to be more reactogenic 53 and to induce higher antibody titers in healthy individuals as well as in the more vulnerable elderly population 54, 55 . Similarly to other studies analyzing the factors that were associated to low antibody levels after COVID-19 vaccination in dialysis patients, we also found a few risk factors of defective neutralizing antibody response to mRNA vaccines, including age, heart failure and Our study has some limitations including a missing control group of patients matched by age, gender and comorbidities, without ESKD, while our control group was composed by is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 7, 2021. ; https://doi.org/10.1101/2021.10.05.21264054 doi: medRxiv preprint younger individuals with few or no comorbidities. Another limitation was the low number of PD patients that did not allow to make subgroup analyses of risk factors of defective response. In addition, our patients were unbalanced in terms of type of mRNA vaccine received (BNT162b2 or mRNA-1273), although we had sufficient statistical power to make a comparison, even in a subgroup of patients matched by age, gender and comorbidity index. In conclusion, our study demonstrates, at the functional level, that mRNA vaccines induce a defective neutralizing antibody response against SARS-CoV-2 variants in dialysis patients, in particular in naïve HD patients immunized with BNT162b2. Our findings support the need of an additional boost, preferentially with a high-dose mRNA vaccine, in this population [58] [59] [60] , which, however, need to be continuously monitored with proper serological tests that measure not only the serum antibody levels, but also their neutralizing activity, either directly or indirectly through an avidity test. Finally, our data suggest that some patients may not respond efficiently even after an additional boost and, therefore, in case of SARS-CoV-2 infection, they should be considered for other therapeutic strategies, including early immunotherapy with monoclonal antibodies. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 7, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 7, 2021. ; is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 7, 2021. ; https://doi.org/10.1101/2021.10.05.21264054 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 7, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 7, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 7, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 7, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 7, 2021. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted October 7, 2021. ; https://doi.org/10.1101/2021.10.05.21264054 doi: medRxiv preprint Prevalence of SARS-CoV-2 antibodies in a large nationwide sample of patients on dialysis in the USA: a cross-sectional study Epidemiology of COVID-19 in an Urban Dialysis Center Results from the ERA-EDTA Registry indicate a high mortality due to COVID-19 in dialysis patients and kidney transplant recipients across Europe COVID-19-related mortality in kidney transplant and dialysis patients: results of the ERACODA collaboration UK Renal Registry (2020) COVID-19 surveillance report for renal centres in the UK: All regions and centres Worldwide Early Impact of COVID-19 on Dialysis Patients and Staff and Lessons Learned: A DOPPS Roundtable Discussion Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting SARS-CoV-2 Vaccine Effectiveness in a High-Risk National Population in a Real-World Setting Weak immunogenicity of SARS-CoV-2 vaccine in patients with hematologic malignancies Anti-CD20 therapies decrease humoral immune response to SARS-CoV-2 in patients with multiple sclerosis or neuromyelitis optica spectrum disorders Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients Immune response to SARS-CoV-2 infection and vaccination in patients receiving kidney replacement therapy Practical Guide to Vaccination in All Stages of CKD, Including Patients Treated by Dialysis or Kidney Transplantation Immunogenicity of hepatitis B vaccine among hemodialysis patients: effect of revaccination of non-responders and duration of protection SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion Stabilized coronavirus spikes are resistant to conformational changes induced by receptor recognition or proteolysis Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein Human Immunodeficiency Virus-1 Viral Load Is Elevated in Individuals With Reverse-Transcriptase Mutation M184V/I During Virological Failure of First-Line Antiretroviral Therapy and Is Associated With Compensatory Mutation L74I Creating Insertions or Deletions Using Overlap Extension Polymerase Chain Reaction (PCR) Mutagenesis A system for functional analysis of Ebola virus glycoprotein A Haploid Genetic Screen Identifies Heparan Sulfate Proteoglycans Supporting Rift Valley Fever Virus Infection SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity Defining the features and duration of antibody responses to SARS-CoV-2 infection associated with disease severity and outcome Targeting Zero Infections in Dialysis: New Devices, Yes, but also Guidelines, Checklists, and a Culture of Safety COVID-19 vaccines and kidney disease Immunogenicity of COVID-19 Tozinameran Vaccination in Patients on Chronic Dialysis Humoral and cellular immunity to SARS-CoV-2 vaccination in renal transplant versus dialysis patients: A prospective, multicenter observational study using mRNA-1273 or BNT162b2 mRNA vaccine Immunogenicity of SARS-CoV-2 Vaccine in Dialysis De novo vasculitis after mRNA-1273 (Moderna) vaccination Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection Clinical utility of avidity assays Avidity assay to test functionality of anti-SARS-Cov-2 antibodies The challenge of avidity determination in SARS-CoV-2 serology Role of Toxoplasma gondii IgG Avidity Testing in Discriminating between Acute and Chronic Toxoplasmosis in Pregnancy Comparison of the LIAISON(R)XL and ARCHITECT IgG, IgM, and IgG avidity assays for the diagnosis of Toxoplasma, cytomegalovirus, and rubella virus infections Antibody Response to mRNA-1273 SARS-CoV-2 Vaccine in Hemodialysis Patients with and without Prior COVID-19 Neutralising antibodies after COVID-19 vaccination in UK haemodialysis patients Reactogenicity Following Receipt of mRNA-Based COVID-19 Vaccines Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of Alpha and Delta variant prevalence. medRxiv Neutralizing antibody responses to SARS-CoV-2 variants in vaccinated Ontario long-term care home residents and workers. medRxiv Humoral Response to SARS-CoV-2-Vaccination with BNT162b2 (Pfizer-BioNTech Longevity of SARS-CoV-2 immune responses in hemodialysis patients and protection against reinfection High immunogenicity of a messenger RNA based vaccine against SARS-CoV-2 in chronic dialysis patients Humoral response after 3 doses of the BNT162b2 mRNA COVID-19 vaccine in patients on hemodialysis