anti-S1 IgG Research Articles

Clinical sensitivity and specificity of a high-throughput microfluidic nano-immunoassay combined with capillary blood microsampling for the identification of anti-SARS-CoV-2 Spike IgG serostatus.

We evaluate the diagnostic performance of dried blood microsampling combined with a high-throughput microfluidic nano-immunoassay (NIA) for the identification of anti-SARS-CoV-2 Spike IgG seropositivity. We conducted a serological study among 192 individuals with documented prior SARS-CoV-2 infection and 44 SARS-CoV-2 negative individuals. Participants with prior SARS-CoV-2 infection had a long interval of 11 months since their qRT-PCR positive test. Serum was obtained after venipuncture and tested with an automated electrochemiluminescence anti-SARS-CoV-2 S total Ig reference assay, a commercial ELISA anti-S1 IgG assay, and the index test NIA. In addition, 109 participants from the positive cohort and 44 participants from the negative cohort participated in capillary blood collection using three microsampling devices: Mitra, repurposed glucose test strips, and HemaXis. Samples were dried, shipped by regular mail, extracted, and measured with NIA. Using serum samples, we achieve a clinical sensitivity of 98·33% and specificity of 97·62% on NIA, affirming the high performance of NIA in participants 11 months post infection. Combining microsampling with NIA, we obtain a clinical sensitivity of 95·05% using Mitra, 61·11% using glucose test strips, 83·16% using HemaXis, and 91·49% for HemaXis after automated extraction, without any drop in specificity. High sensitivity and specificity was demonstrated when testing micro-volume capillary dried blood samples using NIA, which is expected to facilitate its use in large-scale studies using home-based sampling or samples collected in the field.

Low humoral and cellular immune responses early after breakthrough infection may contribute to severe COVID-19.

Little is known about the immune determinants for severe coronavirus disease 2019 (COVID-19) in individuals vaccinated against severe acute respiratory syndrome coronavirus 2. We therefore attempted to identify differences in humoral and cellular immune responses between patients with non-severe and severe breakthrough COVID-19. We prospectively enrolled hospitalized patients with breakthrough COVID-19 (severe and non-severe groups) and uninfected individuals who were vaccinated at a similar time (control group). Severe cases were defined as those who required oxygen therapy while hospitalized. Enzyme-linked immunosorbent assays and flow cytometry were used to evaluate humoral and cellular immune responses, respectively. Anti-S1 IgG titers were significantly lower in the severe group than in the non-severe group within 1 week of symptom onset and higher in the non-severe group than in the control group. Compared with the control group, the cellular immune response tended to be diminished in breakthrough cases, particularly in the severe group. In multivariate analysis, advanced age and low anti-S1 IgG titer were associated with severe breakthrough COVID-19. Severe breakthrough COVID-19 might be attributed by low humoral and cellular immune responses early after infection. In the vaccinated population, delayed humoral and cellular immune responses may contribute to severe breakthrough COVID-19.

SARS-CoV-2 IgG seroprevalence surveys in blood donors before the vaccination campaign, France 2020-2021

We conducted a cross-sectional study for SARS-CoV-2 anti-S1 IgG prevalence in French blood donors (n= 32605), from March-2020 to January-2021. A mathematical model combined seroprevalence with a daily number of hospital admissions to estimate the probability of hospitalization upon infection and determine the number of infections while correcting for antibody decay. There was an overall seroprevalence increase over the study period and we estimate that ∼15% of the French population had been infected by SARS-CoV-2 by January-2021. The infection/hospitalization ratio increased with age, from 0.31% (18-30yo) to 4.5% (61-70yo). Half of the IgG-S1 positive individuals had no detectable antibodies 4 to 5months after infection. The seroprevalence in group O donors (7.43%) was lower (p= 0.003) than in A, B, and AB donors (8.90%). We conclude, based on seroprevalence data and mathematical modeling, that a large proportion of the French population was unprotected against severe disease prior to the vaccination campaign.

Comparable efficacy and safety of COVID-19 vaccines for patients receiving tegafur-uracil as postoperative adjuvant chemotherapy.

Many effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed, but a weaker response in individuals undergoing anticancer treatment has been reported. This study evaluates the immunogenic status and safety of SARS-CoV-2 vaccines for patients with non-small-cell lung cancer (NSCLC), receiving tegafur-uracil (UFT) as postoperative adjuvant chemotherapy. The subjects of this prospective study were 40 patients who underwent surgery for NSCLC and received SARS-CoV-2 vaccines postoperatively. We compared the antibody titers of SARS-CoV-2 vaccines and the adverse events between patients who received adjuvant UFT and patients who did not. The mean anti-S1 IgG titers were not significantly different between the UFT and without-UFT groups (mean optimal density, 0.194 vs. 0.205; P = 0.76). Multivariate analysis identified the period after the second vaccination as an independent predictor of anti-S1 IgG titer (P = 0.049), but not the UFT status (with or without-UFT treatment; P = 0.47). The prevalence of adverse events did not differ significantly between the groups, and no severe adverse events occurred. The efficacy and safety of the SARS-CoV-2 vaccines for NSCLC patients who received postoperative adjuvant UFT chemotherapy were comparable to those for NSCLC patients who did not receive postoperative adjuvant UFT chemotherapy. This study was registered with the University Hospital Medical Information Network (UMIN) in Japan (UMIN000047380).

Primary ChAdOx1 vaccination does not reactivate pre-existing, cross-reactive immunity.

Currently available COVID-19 vaccines include inactivated virus, live attenuated virus, mRNA-based, viral vectored and adjuvanted protein-subunit-based vaccines. All of them contain the spike glycoprotein as the main immunogen and result in reduced disease severity upon SARS-CoV-2 infection. While we and others have shown that mRNA-based vaccination reactivates pre-existing, cross-reactive immunity, the effect of vector vaccines in this regard is unknown. Here, we studied cellular and humoral responses in heterologous adenovirus-vector-based ChAdOx1 nCOV-19 (AZ; Vaxzeria, AstraZeneca) and mRNA-based BNT162b2 (BNT; Comirnaty, BioNTech/Pfizer) vaccination and compared it to a homologous BNT vaccination regimen. AZ primary vaccination did not lead to measurable reactivation of cross-reactive cellular and humoral immunity compared to BNT primary vaccination. Moreover, humoral immunity induced by primary vaccination with AZ displayed differences in linear spike peptide epitope coverage and a lack of anti-S2 IgG antibodies. Contrary to primary AZ vaccination, secondary vaccination with BNT reactivated pre-existing, cross-reactive immunity, comparable to homologous primary and secondary mRNA vaccination. While induced anti-S1 IgG antibody titers were higher after heterologous vaccination, induced CD4+ T cell responses were highest in homologous vaccinated. However, the overall TCR repertoire breadth was comparable between heterologous AZ-BNT-vaccinated and homologous BNT-BNT-vaccinated individuals, matching TCR repertoire breadths after SARS-CoV-2 infection, too. The reasons why AZ and BNT primary vaccination elicits different immune response patterns to essentially the same antigen, and the associated benefits and risks, need further investigation to inform vaccine and vaccination schedule development.

Humoral Immune Response to CoronaVac in Turkish Adults.

While most approved vaccines are based on the viral spike protein or its immunogenic regions, inactivated whole-virion vaccines (e.g., CoronaVac) contain additional antigens that may enhance protection. This study analyzes short-term humoral responses against the SARS-CoV-2 spike (S1) and nucleocapsid (NCP) protein in 50 Turkish adults without previous SARS-CoV-2 infection after CoronaVac immunization. Samples were collected before vaccination (t0), 28-29 days after the first vaccine dose and prior to the second dose (t1), as well as 14-15 days after the second dose (t2). Anti-S1 IgG and IgA as well as anti-NCP IgG were quantified using ELISA. At t1, seroconversion rates for anti-S1 IgG, anti-S1 IgA and anti-NCP IgG were 30.0%, 28.0% and 4.0%, respectively, increasing significantly to 98.0%, 78.0% and 40.0% at t2. The anti-NCP IgG median (t2) was below the positivity cut-off, while anti-S1 IgG and IgA medians were positive. Anti-S1 IgG levels strongly correlated with anti-S1 IgA (rs = 0.767, p < 0.001) and anti-NCP IgG (rs = 0.683, p < 0.001). In conclusion, two CoronaVac doses induced significant increases in antibodies against S1 and NCP. Despite strong correlations between the antibody concentrations, the median levels and seroconversion rates of S1-specific responses exceed those of NCP-specific responses as early as two weeks after the second vaccine dose.

312. Performance and validation of an adaptable multiplex assay for detection of serologic response to SARS-CoV-2 infection or vaccination.

Abstract Background A wide array of assays to detect the serologic response to SARS-CoV-2 have been developed since the emergence of the pandemic. The majority of these are either qualitative or semi-quantitative, detect antibodies against one antigenic target, and are not adaptable to new antigens. Methods We developed a new, multiplex immunoassay to detect antibodies against the receptor binding domain, S1 and S2 spike subunits and nucleocapsid (N) antigens of SARS-CoV-2 (the CEPHR SARS-CoV-2 Serology Assay). This assay uses electrochemiluminescence technology which allows for a broad dynamic range, and a linker format which allows for the addition of new antigenic targets. We tested this assay on a series of biobanked samples and validated its performance against the Abbott SARS-CoV-2 IgG and Abbott SARS-CoV-2 IgG II assays, and the MesoScale Diagnostics V-PLEX SARS-CoV-2 Panel 2 Kit. Results Participant demographics are shown in Table 1. The mean (standard deviation (SD)) intra-assay (within plate) coefficient of variation (CV) of 80 plasma samples run on the same plate was 3.9% (2.9) for N, 3.8% (6.2) for RBD, 3.8% (5.9) for S1 and 3.9% (5.3) for S2. The mean (SD) inter-assay CV derived from 5 samples run across 3 days by two different operators was 11% (6.5) for N, 13% (5.7) for RBD, 14% (8.9) for S1 and 13% (5.1) for S2. In the convalescent group (n=193), overall sensitivity for each assay was; RBD 82% (95% CI 76-87), S1 86% (81-91%), S2 88% (83 – 92%) and N 72% (64 – 78%). Sensitivity improved when analysis included only individuals who were sampled more than 14 days from onset of symptoms (n=166), RBD 87% (81 – 95%), S1 91% (85 – 95%), S2 91% (85 – 95%) but not for the N-target (73% (66-80%)). In vaccinated individuals (n = 58), 100% (94-100%) had both detectable RBD and S1 antibodies. Overall specificity was 96% (87-99%) for RBD, 90% (78-97%) for S1, 94% (84-99%) for S2 and 90% (78-97%) for N. There was excellent correlation between the Abbott IgG II and both CEPHR anti-RBD IgG (rho 0.91) and CEPHR anti-S1 IgG (rho 0.9, both p &amp;lt; 0.001, Figure 1.) and the V-PLEX full spike and both CEPHR RBD IgG (rho 0.83) and S1 IgG (rho 0.82, both p &amp;lt; 0.001, Figure 4). Table 1Participant demographics Correlation between CEPHR RBD, Abbott SARS-CoV-2 IgG II anti spike assay and V-PLEX Spike assay. Vertical dashed line represents CEPHR RBD positivity threshold, horizontal dashed line indicates Abbott positivity threshold. B: Correlation between CEPHR RBD and MSD V-PLEX Spike IgG. Vertical dashed line represents CEPHR RBD positivity threshold, no positivity threshold provided by MSD. Conclusion The CEPHR SARS-CoV-2 Serology Assay is a robust, customisable, multiplex serologic assay for the detection of several different IgG specific to SARS-CoV-2. Disclosures All Authors: No reported disclosures.

The third inactivated vaccine booster dramatically enhanced SARS-CoV-2 antibody responses and did not influence the profile of prothrombotic antibody.

The purpose of this study is to investigate the production of both severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2)-specific antibodies and autoantibodies in serum following the third booster vaccination of the inactivated COVID-19 vaccine, and to study the effect of B cell subsets with CD27 and CD38 phenotypes in peripheral blood on antibody production.Routine blood indexes, SARS-CoV-2 antibodies, platelet factor 4 and seven antiphospholipid antibodies were detected both before and 2 months after vaccination in the medical staff of the Zhongnan Hospital of Wuhan University. Peripheral blood B cell subtypes were detected before vaccination.Following immunization, the positive rate of anti-N-S1 immunoglobulin (IgG) had increased from 24.8% to 91.3% and the average antibody concentration had increased by 11 times. The positive rate of neutralizing antibodyhad increased from 24.8% to 91.3%, the average antibody concentration had increased by 12 times, and the primary increased anti-S1 IgG subtype was that of IgG1. Peripheral blood CD27 + CD38+B cells were positively correlated with antibody levels after vaccination and were a predictor of the antibody response. In addition, although some indicators showed slight absolute changes, the blood parameters and antiphospholipid antibodies of most volunteers were normal both before and after COVID-19 inactivated vaccine inoculation, and there was no statistical difference in abnormal rates either before or after inoculation.Antibodies in vivo were increased after vaccination with the inactivated vaccine, and IgG1 was the main subtype involved in response to the vaccine. Vaccination with the inactivated COVID-19 vaccine did not appear to affect thrombus-related autoantibodies.

Humoral response and safety of the BNT162b2 and mRNA-1273 COVID-19 vaccines in allogeneic hematopoietic stem cell transplant recipients: An observational study

BackgroundThe effectiveness of mRNA COVID-19 vaccines and the optimal timing of vaccine administration in allogeneic hematopoietic stem cell transplantation (Allo-HSCT) recipients remains inadequately investigated. We examine the effectiveness and safety of mRNA COVID-19 vaccines in allo-HSCT recipients. MethodThis prospective observational study included 44 allo-HSCT recipients and 38 healthy volunteers. The proportion of subjects acquiring anti-S1 IgG antibodies were considered as the primary endpoint. The occurrence of adverse events after vaccination and objective deterioration of chronic graft-versus-host disease (GVHD) were defined as secondary endpoints. In addition, we compared the geometric mean titers (GMT) of anti-S1 antibody titers in subgroups based on time interval between transplantation and vaccination. ResultsA humoral response to the vaccine was evident in 40 (91%) patients and all 38 healthy controls. The GMT of anti-S1 titers in patients and healthy controls were 277 (95% confidence interval [CI]: 120–643) BAU/mL and 532 (95% CI 400–708) BAU/mL, respectively. (p = 0.603). A short time interval between transplantation and vaccination (≤6 months) was associated with low anti-S1 IgG antibody titers. No serious adverse events and deterioration of chronic GVHD were observed. Only one case of new development of mild chronic GVHD was recorded. ConclusionMessenger RNA COVID-19 vaccines induce humoral responses in allo-HSCT recipients and can be administered safely.

Booster Dose of mRNA-Based COVID-19 Vaccine Induces a Humoral and Cellular Response in Patients Recently Treated with Anti-CD20 Monoclonal Antibodies

Patients with hematological diseases receiving an anti-CD20 monoclonal antibody, such as rituximab or obinutuzumab (R/Obi), show a low seroconversion rate after two doses of mRNA COVID-19 vaccines, especially if received within 12 months of their last R/Obi dose. The Centers for Disease Control and Prevention recommend booster vaccination at least three months after completing the primary series for immunocompromised patients. Although previous reports have shown that some non-responders achieved a humoral response after the third dose, the seroconversion rate was approximately 20%. In these studies, the interval between booster vaccination and the last R/Obi dose was shorter than six months, suggesting that the unsatisfactory seroconversion rate may be due to a lack of B cell recovery. In Japan, a third dose was offered seven months after the second vaccination, regardless of the immunosuppressive status, in early 2022. Booster vaccination at longer intervals may induce a higher humoral response rate in patients recently treated with R/Obi. However, only a few studies have examined this issue. In addition, the data on T cell responses after booster vaccination in these patients are limited. Therefore, this study aimed to investigate the humoral and cellular reactions of R/Obi receivers to mRNA COVID-19 vaccines, which were administered at an interval longer than that in Western countries. This study included 68 patients with hematological diseases who had received the primary vaccine series within 12 months of their last R/Obi dose and 30 healthy volunteers. Blood samples were collected before and 14-90 days after the booster vaccination. We set the primary endpoint as the proportion of subjects acquiring IgG antibodies to the S1 subunit of the spike protein of SARS-CoV-2 (anti-S1 IgG antibody; Abbott, Sligo, Ireland) with a range of 7.1-5,680 binding antibody units per mL (BAU/mL). Seropositivity was defined as anti-S1 IgG antibodies >7.1 BAU/mL. As secondary endpoints, we also evaluated the T cell response to SARS-CoV-2 in patients using an enzyme-linked immunospot assay (T-SPOT. COVID, Oxford Immunotec), with positivity defined as more than 20 spots/well. Fifty-two patients (median age 73 years) ｗhose data were available for analysis after data collection and 30 volunteers (median age 32 years) were included in the analysis. Twenty-one (40%) patients were diagnosed with diffuse large B-cell lymphoma, 16 (31%) with follicular lymphoma, 14 (27%) with other B-cell neoplasms, and one with benign hematological disease. Forty-four (85%) patients were in complete remission (CR), two were not in CR, and six (12%) were on R/Obi maintenance therapy. The median time from the second to the third vaccination was 223 days. The seropositivity rate before the booster vaccination was 12% and 100% in patients and volunteers, respectively, with median anti-S1 IgG titers of 0 (interquartile, IQR 0-0) and 82 (IQR 47-143) BAU/mL, respectively. (Fig.1A) After booster vaccination, the seropositivity rates were 42% and 100% in patients and volunteers, respectively, with median titers of 0 (IQR 0-89) and 2,504 (IQR 1,376-3,121) BAU/mL, respectively. (Fig.1A) The T cell response before booster vaccination was observed in 13 (25%) patients, all of whom were seronegative. (Fig.1B) After booster vaccination, it was detected in 22 (42%) patients, including 13 seronegative patients. (Fig.1B) All six patients on maintenance therapy remained seronegative; however, two patients showed T cell response before and four after a third dose, respectively. In total, either humoral or cellular response before booster vaccination was identified in 37% of patients, which increased to 67% after booster vaccination. Booster vaccination within a seven-month interval induced a humoral response in 42% of patients recently receiving R/Obi, and the T-cell response was identified and enhanced in some seronegative patients. Around 70% of patients showed humoral, cellular, or both response after booster vaccination. These results provide insights into the rational vaccination strategy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Post-COVID-19 vaccine SARS-CoV-2 antibody investigation in healthcare professionals

Objectives: Main purpose of this study was evaluating inactive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine subsequent anti-S1 IgG feedback and the aspects involved in such reactions for professionals in healthcare (HCP) as the dominant risk group.Methods: Thirty-six HCPs with previous COVID-19 infection and 164 with no priors, 200 in total, who was working in the Ankara Public Health Molecular Diagnosis Laboratory were included. Main tool of identifying humoral immune response quantifably in serum samples which were obtained 28 days after administering each of two doses of vaccine was Roche Elecsys SARS-CoV-2 kit. Results: Average antibody levels of 164 negative HCPs were 15.82 ± 8.59 IU/mL and 26.042 ± 10.73 IU/mL while 36 positive HCPs demonstrated antibody responses as 66.083 ± 33.927 IU/mL and 90 ± 27.012 IU/mL 28 days after each of two doses of vaccine for both individual groups respectively. A statistically meaningful difference was found in antibody levels after two vaccine doses in both groups (p &amp;lt; 0.0001). The authors observed statistically higher average antibody levels after initial vaccine dosage in HCPs with infection than the antibody levels of naive individuals after second dose (p &amp;lt; 0.0001). Age, gender and vaccination feedback did not have a statistically meaningful disparity (p &amp;gt; 0.05). Conclusions: It was concluded that the average antibody level achieved after inital dose n HCPs with COVID-19 infection was surpassing the average antibody level obtained after the second dose in naive HCPs. The authors recommend further clinical researches on antibody levels and the extent of protection to prohibit COVID-19

Humoral and Cellular Immune Responses against SARS-CoV-2 after Third Dose BNT162b2 following Double-Dose Vaccination with BNT162b2 versus ChAdOx1 in Patients with Cancer.

Patients with cancer display reduced humoral responses after double-dose COVID-19 vaccination, whereas their cellular response is more comparable with that in healthy individuals. Recent studies demonstrated that a third vaccination dose boosts these immune responses, both in healthy people and patients with cancer. Because of the availability of many different COVID-19 vaccines, many people have been boosted with a different vaccine from the one used for double-dose vaccination. Data on such alternative vaccination schedules are scarce. This prospective study compares a third dose of BNT162b2 after double-dose BNT162b2 (homologous) versus ChAdOx1 (heterologous) vaccination in patients with cancer. A total of 442 subjects (315 patients and 127 healthy) received a third dose of BNT162b2 (230 homologous vs. 212 heterologous). Vaccine-induced adverse events (AE) were captured up to 7 days after vaccination. Humoral immunity was assessed by SARS-CoV-2 anti-S1 IgG antibody levels and SARS-CoV-2 50% neutralization titers (NT50) against Wuhan and BA.1 Omicron strains. Cellular immunity was examined by analyzing CD4+ and CD8+ T-cell responses against SARS-CoV-2-specific S1 and S2 peptides. Local AEs were more common after heterologous boosting. SARS-CoV-2 anti-S1 IgG antibody levels did not differ significantly between homologous and heterologous boosted subjects [GMT 1,755.90 BAU/mL (95% CI, 1,276.95-2,414.48) vs. 1,495.82 BAU/mL (95% CI, 1,131.48-1,977.46)]. However, homologous-boosted subjects show significantly higher NT50 values against BA.1 Omicron. Subjects receiving heterologous boosting demonstrated increased spike-specific CD8+ T cells, including higher IFNγ and TNFα levels. In patients with cancer who received double-dose ChAdOx1, a third heterologous dose of BNT162b2 was able to close the gap in antibody response.

Antibody and T-Cell Subsets Analysis Unveils an Immune Profile Heterogeneity Mediating Long-term Responses in Individuals Vaccinated Against SARS-CoV-2.

Based on the fact that coronavirus disease 2019 (COVID-19) is still spreading despite worldwide vaccine administration, there is an imperative need to understand the underlying mechanisms of vaccine-induced interindividual immune response variations. We compared humoral and cellular immune responses in 127 individuals vaccinated with either BNT162b2, mRNA-1273, or ChAdOx1-nCoV-19 vaccine. Both mRNA vaccines induced faster and stronger humoral responses as assessed by high spike- and RBD-specific antibody titers and neutralizing efficacy in comparison to ChAdOx1-nCoV-19 vaccine. At 7 months postvaccination, a decreasing trend in humoral responses was observed, irrespective of the vaccine administered. Correlation analysis between anti-S1 IgG and interferon- (IFN-) production unveiled a heterogeneous immune profile among BNT162b2-vaccinated individuals. Specifically, vaccination in the high-responder group induced sizable populations of polyfunctional memory CD4 helper T cells (TH1), follicular helper T cells (TFH), and T cells with features of stemness (TSCM), along with high neutralizing antibody production that persisted up to 7 months. In contrast, low responders were characterized by significantly lower antibody titers and memory T cells and a considerably lower capacity for interleukin-2 and IFN- production. We identified that long-term humoral responses correlate with the individuals ability to produce antigen-specific persistent memory T-cell populations.

210.13: Humoral Response to SARS-COV-2 Vaccination in Kidney Transplant Recipients

Introduction: We sought to evaluate the humoral response to SARS-CoV-2 vaccination in a cohort of kidney transplant (KT) recipients and to identify factors associated with poor humoral immune response. Method: Serum samples collected from COVID-19 vaccinated kidney transplant (KT) recipients from 3/1/21-4/26/21 were tested for COVID-19 antibodies using a novel multi-antigen detection Luminex platform (BioRad). We measured the specific anti-SARS-CoV-2 IgG antibodies against the individual components of the trimeric spike protein, namely spike 1 (S1), spike 2 (S2) and receptor-binding domains (RBDs). In addition, documentation of previous infection was assessed by measuring anti-nucleocapsid antibodies. Results: The study cohort enrolled 104 KT recipients that underwent assessment of serological responses at a median 3 weeks (IQR: 1.6-4.9) after vaccination. The majority of patients received either the BNT162b2 (50%) or mRNA-1273 (47.1%), with only 2.9% of patients receiving the Ad26.COV2.S vaccine. Overall, 32.7% of patients became seropositive with a median anti-S1 IgG and anti-RBD IgG levels of 403 BAU/ml (IQR:82-800) and 206 BAU/ml (IQR:41-800). In terms of predictive factors for vaccine response, we identified that those on an immunosuppressive regimen containing MMF were less likely to develop a seroconversion (relative risk [RR], 0.54 [95% CI, 0.31-0.94]; p=0.03). By contrast, patients with evidence of previous infection as documented by anti-nucleocapsid positivity were significantly more likely to became seropositive (RR, 2.73; 95%CI, 1.7-4.39; p<0.001). Regarding the temporal evolution of humoral response, there is a clear tendency for a weaning of antibody response over time. In patients with a vaccine response, the median titer of anti-RBD antibodies decreased from 800 BAU/ml (IQR:257-800), in patients with serum samples within 2 weeks after vaccination, to 168 BAU/ml (IQR:74-641), in patients with samples taken after more than 4 weeks post-vaccination (p=0.15). Similarly, the anti-S1 IgG antibody titers were higher in patients with serum samples taken early after vaccination [636 BAU/ml (IQR:276-800), for 0-2 weeks; 579 BAU/ml (IQR:39-800), for 2-4 weeks and 97 BAU/ml (IQR:37-251) for > 4 weeks; p=0.05]. In multivariate logistic regression analysis, we identified the presence of anti-nucleocapsid IgG antibodies as being independently associated with approximately 8-fold higher chance for a seroconversion (HR, 7.96; 95%CI, 1.26-50.1), while use of MMF-containing immunosuppressive regimens decreased the chance of humoral response by approximately 66% (HR, 0.34; 95%CI, 0.1-1.11). Conclusion: Kidney transplant recipients have a poor humoral immune response to a two-dose regimen of SARS-CoV-2 vaccine. Previous natural infection increase the likelihood for development a seroconversion, while MMF-containing regimens decreased vaccine responsiveness.

Assessment of humoral immune response to two mRNA SARS-CoV-2 vaccines (Moderna and Pfizer) in healthcare workers fully vaccinated with and without a history of previous infection.

AimsPresence of anti‐S1 region of SARS‐CoV‐2 spike protein was analysed, at two and eight months, in 477 immunocompetent healthcare workers in Zaragoza, Spain, vaccinated with mRNA‐1273 (Moderna) or BNT162b2 (Pfizer).Methods and resultsAntibody analysis was performed with Alinity i System (Abbott). At 2 months, 100% of vaccinated had anti‐S1 IgG (mean = 13,285 AU ml−1). This value was significantly higher with Moderna (18,192 AU ml−1) than with Pfizer (10,441 AU ml−1). The mean value of anti‐S1 IgG after vaccination was significantly higher in patients with than without previous infection (18,539 vs. 7919 AU ml−1); in both groups was significantly higher with Moderna than with Pfizer (21,881 vs. 15,733 AU ml−1 and 11,949 vs. 6387 AU ml−1), respectively. At 8 months, 100% of patients were IgG positive, with higher levels with Moderna than with Pfizer. Nevertheless, in ensemble of cases, a mean decrease of antibody levels of 11,025 AU ml−1 was observed.ConclusionAt 2 and 8 months after vaccination, IgG response persists with both vaccines but with important decrease which suggests the need for revaccination.Significance and impact of studyThe study contributes to know the immune status after vaccination with two of more used anti‐SARS‐CoV‐2 vaccines. This knowledge is important for establishing the best vaccination strategy

1666P Lower virus neutralizing titers against SARS-CoV-2 Omicron strain after third dose BNT162b2 following primo-vaccination with ChAdOx1 versus BNT162b2 in cancer patients

Cancer patients display reduced humoral responses after initial COVID-19 vaccination. Although vaccination protects against severe COVID-19, T cell immunity is impaired in cancer patients. In recent studies, booster vaccines provide additional protection against SARS-CoV-2. However, more data is needed on different vaccination schedules. This prospective study compares BNT162b2 booster-vaccination after primo-vaccination with BNT162b2 (homologous) versus ChAdOx1 (heterologous) in cancer patients. 441 subjects (314 cancer patients and 127 healthy individuals) received a 3rd dose BNT162b2 (229 homologous vs 212 heterologous) 6-9 months after priming. Vaccine induced adverse events (AE) were captured up to 7 days after vaccination. Humoral immunity was assessed by SARS-CoV-2 anti-S1 IgG antibody levels and SARS-CoV-2 50% neutralization titers (NT50) for Wuhan and Omicron strains. Cellular immunity was examined by analyzing CD4 and CD8 T cell responses against SARS-CoV-2 specific S1 and S2 peptides. All assays were performed on blood samples collected 28 days after 3rd dose. Local AEs were more common after heterologous boosting, while no significant differences were seen for systemic AEs. SARS-CoV-2 anti-S1 IgG antibody levels did not differ significantly between homologous and heterologous boosted subjects (GMT 1755.90 BAU/ml [95% C) 1276.95-2414.48] vs 1495.82 BAU/ml (95% CI 1131.48-1977.46)). However, homologously boosted subjects show significantly higher NT50 values against Omicron. T cell responses were assessed by CD154 (CD40L) and CD137 expression on CD4 and CD8 T cells as general markers of antigen-specific stimulation. Here, no significant differences in T cell responses and cytokine levels of IFNγ, IL-2 and TNFα were observed between both boosting regimens. Homologous and heterologous boosted patients elicit similar SARS-CoV-2 anti-S1 IgG antibody levels. Yet, heterologous boosted subjects report more local AEs and homologous boosted subjects show significantly higher NT50 values against Omicron. No difference between T cell responses in heterologous and homologous boosted cohorts was observed.

Low quantity and quality of anti-spike humoral response is linked to CD4 T-cell apoptosis in COVID-19 patients

In addition to an inflammatory reaction, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-infected patients present lymphopenia, which we recently reported as being related to abnormal programmed cell death. As an efficient humoral response requires CD4 T-cell help, we hypothesized that the propensity of CD4 T cells to die may impact the quantity and quality of the humoral response in acutely infected individuals. In addition to specific immunoglobulins (Ig)A, IgM, and IgG against SARS-CoV-2 nucleocapsid (N), membrane (M), and spike (S1) proteins, we assessed the quality of IgG response by measuring the avidity index. Because the S protein represents the main target for neutralization and antibody-dependent cellular cytotoxicity responses, we also analyzed anti-S-specific IgG using S-transfected cells (S-Flow). Our results demonstrated that most COVID-19 patients have a predominant IgA anti-N humoral response during the early phase of infection. This specific humoral response preceded the anti-S1 in time and magnitude. The avidity index of anti-S1 IgG was low in acutely infected individuals compared to convalescent patients. We showed that the percentage of apoptotic CD4 T cells is inversely correlated with the levels of specific IgG antibodies. These lower levels were also correlated positively with plasma levels of CXCL10, a marker of disease severity, and soluble Fas ligand that contributes to T-cell death. Finally, we found lower S-Flow responses in patients with higher CD4 T-cell apoptosis. Altogether, these results demonstrate that individuals with high levels of CD4 T-cell apoptosis and CXCL10 have a poor ability to build an efficient anti-S response. Consequently, preventing CD4 T-cell death might be a strategy for improving humoral response during the acute phase, thereby reducing COVID-19 pathogenicity.

Indoxyl Sulfate Alters the Humoral Response of the ChAdOx1 COVID-19 Vaccine in Hemodialysis Patients.

Background and aims: Vaccination for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is strongly recommended. The efficacy of SARS-CoV-2 vaccine for patients with end-stage renal disease is low. Indoxyl sulfate (IS) is a representative protein bound uremic toxin arousing immune dysfunction in CKD patients. It is unknown whether IS impairs the efficacy of vaccines for SARS-CoV-2. Materials and Methods: From 1 June 2021, to 31 December 2021, hemodialysis patients (n = 358) and a control group (n = 59) were eligible to receive the first dose of the ChAdOx1 COVID-19 vaccine. Titer measurements indicative of the humoral response (anti-S1 IgG and surrogate virus neutralization test (sVNT) results) and indoxyl sulfate concentration measurement were performed 4 weeks after ChAdOx1 vaccine injection. Results: The serum concentrations of anti-S1 IgG were 272 ± 1726 AU/mL and 2111 ± 4424 AU/mL in hemodialysis patients and control group (p < 0.05), respectively. The sVNT values were 26.8 ± 21.1% and 54.0 ± 20.2% in the hemodialysis and control groups (p < 0.05), respectively. There was a decreasing trend for the anti-S1 IgG titer from the lowest to highest quartile of IS (p < 0.001). The patients with higher concentrations of IS had lower sVNT (p for trend < 0.001). Conclusion: Hemodialysis patients had weaker humoral immunity after the first dose of the ChAdOx1 vaccine. Higher concentration of IS altered the development of anti-S1 antibodies and sVNT-measured neutralization.

SARS-CoV-2 mRNA vaccinations fail to elicit humoral and cellular immune responses in patients with multiple sclerosis receiving fingolimod

BackgroundSARS-CoV-2 mRNA vaccination of healthy individuals is highly immunogenic and protective against severe COVID-19. However, there are limited data on how disease-modifying therapies (DMTs) alter SARS-CoV-2 mRNA vaccine immunogenicity in...

Variant Allele of ALDH2, rs671, Associates with Attenuated Post-Vaccination Response in Anti-SARS-CoV-2 Spike Protein IgG: A Prospective Study in the Japanese General Population.

Uncovering the predictors of vaccine immunogenicity is essential for infection control. We have reported that the most prevalent polymorphism of the aldehyde dehydrogenase 2 gene (ALDH2), rs671, may be associated with an attenuated immune system. To test the inverse relationship between rs671 and antibody production after COVID-19 vaccination, the levels of anti-SARS-CoV-2 Spike protein S1 subunit (S1) IgG were repeatedly measured for four months before and after vaccination with BNT162b2 or mRNA-1273, in 88 Japanese workers and students (including 45 females, aged 21–56 years, with an rs671 variant allele frequency of 0.3). The mixed model including fixed effects of the vaccine type, weeks post vaccination (categorical variable), sex, age, height, smoking status, ethanol intake, exercise habit, perceived stress, steroid use, allergic diseases, and dyslipidemia, indicated an inverse association between log-transformed anti-S1 IgG levels and the number of rs671 variant alleles (partial regression coefficient = −0.15, p = 0.002). Our study indicated for the first time that the variant allele of ALDH2, rs671, is associated with the attenuated immunogenicity of COVID-19 mRNA vaccines. Our finding may provide a basis for personalized disease prevention based on a genetic polymorphism that is prevalent among East Asians.