Median Antibody Titer Research Articles

Decline of Humoral Responses 6 Months after Vaccination with BNT162b2 (Pfizer-BioNTech) in Patients on Hemodialysis.

This study analyzed binding and neutralizing antibody titers up to 6 months after standard vaccination with BNT162b2 (two doses of 30 µg each) in SARS-CoV-2 naïve patients (n = 59) on hemodialysis. Humoral vaccine responses were measured before and 6, 12, and 24 weeks after the first vaccination. A chemiluminescent immunoassay (CLIA) was used to quantify SARS-CoV-2 IgG against the spike glycoprotein. SARS-CoV-2 neutralizing activity was tested against the wild-type virus. A multivariable binary regression model was used to identify risk factors for the absence of humoral immune responses at 6 months. At week 6, vaccine-specific seroconversion was detected in 96.6% of all patients with median anti-SARS-CoV-2 IgGs of 918 BAU/mL. At weeks 12 and 24, seroconversion rates decreased to 91.5% and 79.7%, and corresponding median binding antibody titers declined to 298 BAU/mL and 89 BAU/mL, respectively. Neutralizing antibodies showed a decay from 79.6% at week 6 to 32.8% at week 24. The risk factor with the strongest association for vanishing immune responses was low serum albumin (p = 0.018). Regarding vaccine-specific humoral responses 6 months after the standard BNT162b2 vaccination schedule, SARS-CoV-2 naïve patients receiving hemodialysis must be considered at risk of becoming infected with SARS-CoV-2 and being infectious.

Seroepidemiology of SARS-CoV-2 in pediatric population during a 16-month period prior to vaccination.

Limited prospective serosurveillance data in children regarding severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection have been reported. We prospectively investigated SARS‐CoV‐2 seropositivity in children during a 16‐month period of the coronavirus disease 2019 (COVID‐19) pandemic, including the four waves of the pandemic, before SARS‐CoV‐2 adolescents' vaccination. Serum samples from children admitted to the major tertiary Greek pediatric hospital for any cause, except for COVID‐19 infection, were randomly collected from 05/2020 to 08/2021. The study period was divided into four 4‐month periods representing relevant epidemic waves. Total SARS‐CoV‐2 antibodies for nucleocapsid protein were determined using the Elecsys® Anti‐SARS‐CoV‐2 reagent. A total of 3099 children (0–16 years) were included in the study. A total of 344 (11.1%) seropositive children were detected (males: 205 [59.5%]; median age [interquartile range [IQR]]: 3 years [0.6–10]). Seropositivity rates (%) increased during the four 4‐month periods: 1.4%, 8.6%, 17.2%, and 17.6%, respectively. A correlation of seropositivity rates in children with new diagnosed SARS‐CoV‐2 cases in the community was detected. No significant differences were detected between males and females. Seropositivity was significantly higher in hospitalized than in nonhospitalized children and in non‐Greek compared to Greek children (p < 0.001). The lowest seropositivity rate before school opening (9/2021) was detected in the age groups 6–12 years (14.4%) and 12–16 years (16.1%). However, compared with the other age groups, the lowest median antibody titers were observed in children 0–1 year (median [IQR]: 13.9 cut‐off index: [4.5–53.9] [p < 0.001]). Although the seropositivity of children was related to the community epidemic waves, the exposure was limited. Low seropositivity rates in school‐age children support the need for SARS‐CoV‐2 immunization.

Does smoking have an impact on the immunological response to COVID-19 vaccines? Evidence from the VASCO study and need for further studies

ObjectivesThe aim of this study was to investigate the possible impact of smoking on the humoral response to the BNT162b2 mRNA COVID-19 vaccine (also known as the BioNTech-Pfizer COVID-19 vaccine). Study designA longitudinal sero-epidemiological study was conducted in sample of Italian healthcare workers (HCWs). MethodsHCWs who were administered two doses of the BNT162b2 mRNA vaccine, 21 days apart, between December 2020 and January 2021, were invited to undergo multiple serology tests to identify SARS-CoV-2 S-RBD-specific immunoglobulin G (IgG) antibodies. Participants also responded to questions about their smoking status (i.e. current smokers vs non-smokers) in a survey. ResultsSixty days after the completion of the vaccination cycle, serological analyses showed a difference in vaccine-induced IgG titre between current smokers and non-smokers, with median antibody titres of 211.80 AU/mL (interquartile range [IQR] 149.80–465.50) and 487.50 AU/mL (IQR 308.45–791.65) [P-value = 0.002], respectively. This significant difference in vaccine-induced IgG titres between current smokers and non-smokers remained after adjusting for age, sex, and previous infection with SARS-CoV-2. ConclusionsThis study observed that vaccine-induced antibody titres decrease faster among current smokers than non-smokers. Further research to investigate the impact of smoking on the immunological response to COVID-19 and non-COVID-19 vaccines is required.

DOP27 Humoral immune response after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases treated with immunosuppressive therapy - a Target to B! study

BackgroundThe aim of this study was to investigate the effect of various immunosuppressants on the humoral immune responses after vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs).MethodsThe Target to B! SARS-CoV-2 study is a multicentre study, taking place in 7 Dutch academic hospitals. Patients with the following IMIDs were recruited: Crohn’s disease (CD), ulcerative colitis (UC), auto-immune hepatitis, rheumatic (e.g. rheumatoid arthritis), neurological (e.g. multiple sclerosis) and dermatological IMIDs (e.g. atopic dermatitis). Patients were recruited based on immunosuppressants (table 1) and previous SARS-CoV-2 infection. The control group consisted of healthy subjects and IMID patients without immunosuppressants. SARS-CoV-2 receptor binding domain (RBD) antibodies were measured 28 days after completed SARS-CoV-2 vaccination. Seroconversion was defined as anti-RBD IgG >4 AU/mL. In this abstract, we focus on therapies relevant for inflammatory bowel diseases (IBD) and present results for these treatments from patients with IBD, but also other IMIDs.Results Numbers of recruited patients with each immunosuppressant are shown in table 1. Amongst these patients, 312 patients had CD and 176 UC, the rest was diagnosed with another IMID. Seroconversion was reduced in patients receiving sphingosine 1-phosphate (S1P) modulators (all multiple sclerosis patients) while seroconversion was similar to controls in the other treatment groups. However, use of Anti-tumour necrosis factor (TNF), methotrexate, janus kinase (JAK) inhibitor monotherapy and all combination therapies (except for corticosteroids combined with other immunosuppressants) were associated with reduced Sars-CoV-2 antibody titres. Patients with a previous SARS-CoV-2 infection had higher median antibody titres after second vaccination than those without a previous SARS-CoV-2 infection. The type of IMID did not affect seroconversion rates.ConclusionNo immunosuppressant, registered for IBD, reduced the rates of seroconversion after vaccination against SARS-CoV-2. Some immunosuppressants were associated with lower antibody titres. However, the clinical relevance of lower antibody titres remains unknown. S1P modulators, had a clear negative impact on the humoral response against SARS-CoV-2 after vaccination. This might be relevant in the future as this therapy is currently being approved for UC. Disease aetiology did not impair immunity against SARS-CoV-2 immunity after vaccination. Disclaimer: Absolute numbers of antibody titres and rates of seroconversion will be reported at the conference and are not reported in this abstract as this might negatively impact the current submission process.

SEROLOGICAL RESPONSES TO SARS-COV-2 VACCINATION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A PROSPECTIVE COHORT STUDY

The immune response of SARS-CoV-2 vaccines is uncertain in those with Inflammatory Bowel Disease (IBD) due to a diverse array of immune-modifying therapies that vary in the mechanism of immunosuppression. We aimed to quantify the serological response to SARS-CoV-2 vaccines in those with IBD and determine antibody levels across varying therapeutic options. Individuals with IBD who received first and/or second dose of a COVID-19 vaccine (Pfizer-BioNTech, Moderna, and/or AstraZeneca) were assessed for serological response (2–4 weeks after first dose; 2–8 weeks after second dose and 8–18 weeks after second dose) using the SARS-CoV-2 IgG II Quant assay to the spike protein of SARS-CoV-2. The cohort was stratified based on age, sex, vaccine received, IBD type, IBD therapeutic, and prior confirmed diagnosis of COVID-19. The primary outcome was seroconversion defined as IgG levels of ≥50 AU/mL. Secondarily, we evaluated the geometric mean titer (GMT) with 95% confidence intervals (CI). Table 1 describes the characteristics of individuals with IBD (n=464) with serological data following the first dose (n=266) and/or second dose (n=303) of a COVID-19 vaccine. After the first dose of the vaccine, 81.6% seroconverted, with the lowest first-dose conversion rates in patients taking anti-TNF monotherapy (79.7%), anti-TNF combination therapy (52.9%), and corticosteroids (50.0%) (Table 1). Overall, 98.4% of the cohort seroconverted within 2–8 weeks of the second dose, with 94.6% seropositive within 8–18 weeks of the second dose. Seroconversion after second dose was consistently high across all medication classes (range: 94.6%–100.0%), except for oral corticosteroids (62.5%). GMT levels significantly increased (p<0.0001) from first dose (1679 AU/mL) to second dose at 2–8 week (7943 AU/mL) but fell significantly (<0.0001) to 3565 AU/mL 8–18 weeks from second dose (Table 1, Figure 1). GMT levels 2–8 weeks after second dose were higher in those with prior COVID-19 (12,729 AU/mL), but lower in those receiving anti-TNF combination therapy (4231 AU/mL) and oral corticosteroids (5996 AU/mL) (Table 1). Seroconversion rates following full-regimen vaccination are high in patients with inflammatory bowel disease across all medication classes except for anti-TNF combination therapy and oral corticosteroids. Antibody titres and seroconversion rates tend to decrease after 8 weeks post-full vaccination, which is consistent across medication classes.Figure 1Log-transformed anti-SARS-CoV-2 spike antibody concentration per vaccine category. The wide black bar represents the median log antibody titre per vaccine category, while narrow black bars represent bounds of the interquartile range associated with each vaccine category. The solid blue line represents threshold for positive seroconversion [log10(50 AU/mL)].View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Impaired antibody response to COVID-19 vaccination in advanced HIV infection.

Coronavirus disease 2019 (COVID-19) vaccination is reportedly efficient in people with HIV (PWH) but vaccine trials included participants with normal CD4+ T-cell counts. We analyzed seroconversion rates and antibody titers following two-dose vaccination in PWH with impaired CD4+ T-cell counts. We collected retrospective postvaccination SARS-COV-2 serology results available in a university hospital for PWH vaccinated between March and September, 2021 who were tested for antispike antibodies from 8 to 150 days following dose 2. Antibody titers were compared in PWH with CD4+ T-cell count less than 200 cells/μl, 200 < CD4+ T-cell counts < 500 cells/μl and CD4+ T-cell count greater than 500 cells/μl at vaccination. One hundred and five PWH were included: n = 54 in the CD4+ T-cell count less than 500 cells/μl group (n = 18 with CD4+ <200 cells/μl, n = 36 with 200 < CD4+ < 500 cells/μl) and 51 in the CD4+ T-cell count greater than 500 cells/μl group. They received two doses of BNT162b2 (75%), mRNA-1273 (8.5%), or ChAdOx1 nCoV-19 (16.5%). The median time from vaccine dose 2 to serology was consistent across all groups (73 days, interquartile range [29-97], P = 0.14). Seroconversion rates were 100% in the CD4+ T-cell count greater than 500 cells/μl group but 89% in participants with CD4+ T-cell counts less than 500 cells/μl (22 and 5.5% seronegative in the CD4+ T-cell counts <200 cells/μl and 200 < CD4+ < 500 cells/μl groups, respectively). Median antibody titers were 623.8 BAU/ml [262.2-2288] in the CD4+ greater than 500 cells/μl group versus 334.3 BAU/ml [69.9-933.9] in the CD4+ less than 500 cells/μl group (P = 0.003). They were lowest in the CD4+ less than 200 cells/μl group: 247.9 BAU/ml [5.88-434.9] (P = 0.0017) with only 44% achieving antibody titers above the putative protection threshold of 260 BAU/ml. PWH with CD4+ T-cell counts less than 500 cells/μl and notably less than 200 cells/μl had significantly lower seroconversion rates and antispike antibody titers compared with PWH with CD4+ T-cell counts greater than 500 cells/μl, warranting the consideration of targeted vaccine strategies in this fragile population.

Immunogenicity and safety of SARS-CoV-2 vaccine with immunosuppressive agents.

BackgroundWe conducted a prospective study of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) messenger RNA (mRNA) vaccination of children and adolescents who were taking immunosuppressive agents.MethodsTwo doses of SARS‐CoV‐2 mRNA vaccine were administered to patients taking immunosuppressive agents. Titers of SARS‐CoV‐2 spike protein receptor‐binding domain antibodies were measured before and after vaccination. Vaccine failure was defined as a postvaccination antibody titer of <0.8 U/mL. Seroconversion rates, factors associated with antibody titers after vaccination, clinical effectiveness against breakthrough infection, and adverse events were evaluated.ResultsA total of 42 patients (median age, 18.1 years) were enrolled. Immunogenicity was measured in 34. The median SARS‐CoV‐2 spike antibody titer was 329 U/mL (interquartile range [IQR] 50–812 U/mL). Seroconversion (≥0.8 U/mL) was achieved in 29 patients (85%), whereas vaccine failure was diagnosed in 5 (15%). All patients with vaccine failure were recipients of solid organ transplants (SOTs) and were taking two immunosuppressants. The median antibody titer in SOT recipients (57 U/mL) was significantly lower than that in nonrecipients (653 U/mL, p = 0.0002), and that of patients taking two immunosuppressive agents (93 U/mL) was lower than that of patients taking one (506 U/mL, p = 0.003). Breakthrough infection occurred in three patients (7%). Adverse events were nonspecific, and no flares of primary disease or acute rejection in SOT recipients occurred.ConclusionsSARS‐CoV‐2 mRNA vaccine was immunogenic in children and adolescents taking immunosuppressive agents, although SOT recipients and patients taking two immunosuppressive agents tended to show lower postvaccination antibody titers.

Seroconversion and side effects after COVID vaccination among persons with type 2 diabetes in urban, rural, and tribal areas in Kerala, India.

Persons with type 2 diabetes mellitus (T2DM) are at high-risk for COVID-19 infection and are a priority group for vaccination. The objective of this study is to estimate the seroconversion and determine the side effects after COVID-19 vaccination among persons with T2DM in urban, rural, and tribal areas in Kerala. A cross-sectional study was conducted in urban, rural, and tribal field practice areas of a medical college in Central Kerala, among 396 persons with T2DM. The participants were selected by simple random sampling from the 200-250 diabetic patients visiting each health center. Qualitative and quantitative estimation of antibodies were done by WANTAI Ab enzyme-linked immunosorbent assay kit and Abbott SARS COV-2 IgG Quantitative assay, respectively. The mean age of the respondents was 59.40 ± 12.25 years. A majority (65.5%) had received both doses of vaccine. About half (51.5%) experienced side effects after vaccination. Antibodies (IgG or IgM) were detected in 93.2% (95% confidence interval [CI] 90.2, 95.5) of participants. Those with a duration of diabetes ≥5 years, with a single dose of vaccine, were five times (adjusted odds ratio [aOR] - 5.23,95% CI 1.86, 14.66) and four times (aOR - 4.11, 95% CI 1.66, 10.13) more likely, respectively, to be seronegative. Those who took medication for diabetes were protected against a no antibody (aOR - 0.05, 95% CI 0.02, 0.148) response. The median antibody titer in a subset (150) of participants was 365.2 (90-1587) AU/ml. Past COVID infection was an independent determinant of high IgG titers (aOR - 4.95, 95% CI 1.50, 16.36). Reinforcing the importance of vaccination particularly among those with longer duration of diabetes is imperative.

Generation of neutralizing antibodies against Omicron, Gamma and Delta SARS-CoV-2 variants following CoronaVac vaccination.

ABSTRACTVaccination is a fundamental tool to prevent SARS-CoV-2 infection and to limit the COVID-19 pandemic. The emergence of SARS-CoV-2 variants with multiple mutations has raised serious concerns about the ability of neutralizing antibody responses elicited by prior vaccination to effectively combat these variants. The neutralizing capacity against the Gamma, Delta and Omicron variants of sera from individuals immunized with the CoronaVac vaccine remains incompletely determined. The present study evaluated 41 health care workers at the Faculdade de Medicina of the Universidade de Sao Paulo, in Sao Paulo, Brazil, naive to previous SARS- CoV-2 infection, who were vaccinated with two doses of the CoronaVac SARS-CoV-2 vaccine 28 days apart. Neutralizing antibody levels against the Gamma, Delta, and Omicron variants were measured at 32 and 186 days after the second vaccination. We also measured neutralizing antibodies against Omicron in 34 of these individuals following a subsequent booster immunization with the Pfizer vaccine. Quantification of neutralizing antibodies was performed using the Cytopathic Effect-based Virus Neutralization test. Neutralization antibody activity against the Gamma, Delta and Omicron variants was observed in 78.0%, 65.9% and 58.5% of serum samples, respectively, obtained at a mean of 32 days after the second immunization. This decreased to 17.1%, 24.4% and 2.4% of sera having activity against Delta, Gamma and Omicron, respectively, at 186 days post-vaccination. The median neutralizing antibody titers at 32 days were 1:40, 1:20 and 1:20 against Gamma, Delta and Omicron, respectively, and decreased to an undetectable median level against all variants at the later time. A booster immunization with the Pfizer vaccine elicited neutralizing antibodies against Omicron in 85% of subjects tested 60 days after vaccination. We conclude that two doses of the CoronaVac vaccine results in limited protection of short duration against the Gamma, Delta and Omicron SARS-CoV-2 variants. A booster dose with the Pfizer vaccine induced antibody neutralizing activity against Omicron in most patients which was measurable 60 days after the booster.

SARS-CoV-2 seroepidemiology in paediatric population during Delta and Omicron predominance.

Limited prospective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) data in children regarding the impact of Omicron variant in seropositivity have been reported. We investigated SARS-CoV-2 seropositivity in children between 1 September 2021 and 30 April 2022, representing Delta and Omicron predominance periods. Serum samples from children admitted to the major tertiary Greek paediatric hospital for any cause, except for COVID-19, were randomly collected and tested for SARS-CoV-2 natural infection antibodies against nucleocapsid antigen (Elecsys® Anti-SARS-CoV-2 reagent). A total of 506/1312 (38.6%) seropositive children (0-16 years) were detected (males: 261/506(51.6%); median age (IQR): 95.2 months(24-144)). Seropositivity rates (%) increased from Delta to Omicron period from 29.7% to 48.5% (P-value<0.0001). Seropositivity increased for all age groups, except for the age group of 0-1 year (P-value:0.914). The highest seropositivity rate was detected in April 2022 (52.6%) and reached 73.9% specifically for the age group 12-16 years. No significant differences were detected in seropositivity with respect to gender, origin, or hospitalisation status. Median (IQR) antibody titres were higher in the Omicron vs. Delta period in all age groups, especially in 12-16 years [32.2 COI (7-77.1) vs. 11.4 COI(2.8-50.2), P-value:0.009). During Omicron variant period increased SARS-CoV-2 seropositivity was detected in paediatric population, especially in adolescents, implicating either increased transmissibility or reinfection rates.

Humoral response among patients with interstitial lung disease vaccinated with the BNT162b2 SARS-Cov-2 vaccine: a prospective cohort study

BackgroundPatients with interstitial lung disease (ILD) are at high risk of severe COVID-19 infection. Additionally, their anti-inflammatory and antifibrotic treatment may cause immunosuppression. Nevertheless, their ability to mount an adequate immune response to messenger RNA SARS-CoV-2 vaccines was not evaluated. Therefore, we aimed to evaluate the humoral response after the BNT162b2 vaccine among idiopathic pulmonary fibrosis (IPF) patients treated with antifibrotic therapy and among non-IPF ILD patients treated with anti-inflammatory therapy.MethodsWe conducted an observational prospective cohort study to evaluate the level of anti-spike (S-IgG) antibodies after two doses of the BNT162b2 vaccine in patients with ILD. The cohort included 40 patients with idiopathic pulmonary fibrosis (IPF) treated with anti-fibrotic therapy and 29 patients with non-IPF ILD treated with anti-inflammatory therapy. For S-IgG titer measurement, one serology test was drawn from all patients 4–6 months after the second vaccine dose. In addition a control group matched for age and sex was created from a healthy control cohort of 107 patients. The study was conducted in Rabin Medical Center (Israel) between June and August 2021.ResultsAll patients in the anti-fibrotic arm were seropositive (40/40), corresponding to the matched control group (P = 1.0). The anti-fibrotic arm had a significantly lower median antibody titer in comparison to the matched control group (361.10 [IQR, 207–811] AU/ml vs. 820.75 [IQR, 459–1313] AU/ml; P < 0.001). Only 48.3% (14/29) of patients in the anti-inflammatory arm were seropositive in comparison to 100% (29/29) in the healthy control group (P < 0.001). The anti-inflammatory arm had a significantly lower median antibody titer in comparison to the healthy control group (39.6 [IQR, 4.25–165] AU/ml vs. 970.1 [IQR, 505–1926] AU/ml; P < 0.001).ConclusionIPF patients treated with antifibrotic therapy mount an adequate immune response after 2 doses of the BNT162b2 vaccine, and maintain a 100% seropositivity rate 4–6 months after vaccination. However, their antibody titer was reduced in comparison to a healthy control group. Among patients with non-IPF ILD treated with anti-inflammatory therapy, 48% were seronegative 4–6 months after the second vaccine dose. Moreover, treatment with rituximab caused significant immunosuppression, even in comparison to other anti-inflammatory treatments.

Occurrence of Severe SARS-CoV-2 Infection in Fully Vaccinated Solid Organ Transplant Recipients

The present study presents the clinical outcome of SARS-CoV-2 disease in relation to the humoral response in fully vaccinated solid organ transplant (SOT) recipients. Our patient cohort consists of 455 SOT recipients, vaccinated with one of the 2 approved mRNA vaccines. The antibody response was measured 1 month after the second dose, and previously infected patients have been excluded. Of the 449 remaining patients, 15 (3.34%) tested positive, using SARS-CoV-2 polymerase chain reaction. Their mean age was 43.7 ±14.4 years, and median time from transplantation was 7.8 years (1.2-30.2). Eleven patients (73.3%) had been vaccinated with BNT162b2 and 4 (26.7%) with the mRNA1273 vaccine. At the time of infection 9 (60%) patients had a negative (<50 AU/mL) antibody titer, and 6 (40%) had a positive one (>50 AU/mL). Median antibody titer, 27.4± 14.0 days after the second dose, measured at 13 AU/mL (0-7480 AU/mL). Renal function did not appear to be affected by the disease. Τhe mean estimated glomerular filtration rate at diagnosis was 48 ± 15 mL/min, and when in a 29-day (1-101) median follow-up was 53.9± 20.9 mL/min. Of the 15 patients, 7 had mild symptoms and were not hospitalized, and of the remaining 8 (53.3%) who needed hospitalization 7 had severe disease and 2 of them expired. The study confirms the variable and often severe course of coronavirus 2019 infection in SOT recipients, even after their full vaccination, highlighting the need to vaccinate their close relatives and to accelerate the implementation of the booster dose of vaccine.

Seven-Month Analysis of Five SARS-CoV-2 Antibody Assay Results after ChAdOx1 nCoV-19 Vaccination: Significant Decrease in SARS-CoV-2 Antibody Titer.

We investigated the longevity rates of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after a complete ChAdOx1 nCoV-19 vaccination, which are rare and important to estimate their efficacy and establish a vaccination strategy. We assessed the positivity rates and changes of titers before (T0) and at one month (T1), four months (T2), and seven months (T3) after a ChAdOx1 nCoV-19 vaccination using five SARS-CoV-2 antibody assays. A total of 874 serum samples were obtained from 228 (T0 and T1), 218 (T2), and 200 (T3) healthcare workers. The positive rates for all five assays were 0.0–0.9% at T0, 66.2–92.5% at T1, 98.2–100.0% at T2, and 66.0–100.0% at T3. The positive rates at T3 were decreased compared to those at T2. The median antibody titers of all the assays at T3 were significantly decreased compared to those at T2 (860.5 to 232.0 U/mL for Roche total, 1041.5 to 325.5 AU/mL for Abbott IgG, 10.9 to 2.3 index for Siemens IgG, 99.5% to 94.7% for SD Biosensor V1, and 88.5% to 38.2% for GenScript). A third-dose scheme can be considered based on our data generated from five representative assays. Our findings contribute insights into SARS-CoV-2 antibody assays and appropriate vaccination strategies.

Kinetics of SARS-CoV-2-Neutralising Antibodies of Residents of Long-Term Care Facilities.

IntroductionElderly residents of nursing homes (NHs) and long-term care units (LTCUs) have been shown to have a high risk of mortality and morbidity in cases of SARS-CoV-2 infection. The objective of this study was to examine the kinetics of neutralizing antibodies (NAbs) directed against the SARS-CoV-2 virus in residents of the NH and LTCU units of our University Hospital who were identified with positive serology after the first epidemic outbreak.Materials and MethodsThe participants included were sampled every three months for qualitative serological testing, as well as quantitative testing by neutralization tests using retroviral particles containing the S glycoprotein of SARS-CoV-2. Vaccination using the Comirnaty (Pfizer BNT162b2) vaccine begun before the last serological follow-up.ResultsThe median NAb titer in June 2020 was 80 [40; 60] versus 40 [40; 160] three months later, showing a statistically significant decline (p < 0.007), but remained stable between the three- and six-month timepoints (p = 0.867). By nine months after vaccination, we observed a significant difference between vaccinated residents known to have positive serology before vaccination (SERO+, Vacc+) and those vaccinated without having previously shown COVID-19 seroconversion (SERO−, Vacc+), the latter group showing similar titers to the SERO+, Vacc- participants (p=0.166). The median antibody titer in SERO+, Vacc+ patients increased 15-fold following vaccination.DiscussionHumoral immunity against SARS-CoV-2 appears to be persistent in elderly institutionalized patients, with a good post-vaccination response by residents who had already shown seroconversion but a notably diminished response by those who were seronegative before vaccination. To evaluate immunity in its entirety and elaborate a sound vaccination strategy, the cellular immune response via T cells specific to SARS-CoV-2 merits analysis, as this response is susceptible to being affected by immunosenescence.

Attenuation of Antibody Titers from 3 to 6 Months after the Second Dose of the BNT162b2 Vaccine Depends on Sex, with Age and Smoking Risk Factors for Lower Antibody Titers at 6 Months.

Objective: We aimed to determine antibody titers at six months and their percentage change from three to six months after the second dose of the BNT162b2 coronavirus disease 2019 (COVID-19) mRNA vaccine (Pfizer/BioNTech) and to explore clinical variables associated with titers in Japan. Methods: We enrolled 365 healthcare workers (250 women, 115 men) whose three-month antibody titers were analyzed in our previous study and whose blood samples were collected 183 ± 15 days after the second dose. Participant characteristics, collected previously, were used. The relationships of these factors with antibody titers at six months and percentage changes in antibody titers from three to six months were analyzed. Results: Median age was 44 years. Median antibody titer at six months was 539 U/mL. Older participants had significantly lower antibody titers (20s, 752 U/mL; 60s–70s, 365 U/mL). In age-adjusted analysis, smoking was the only factor associated with lower antibody titers. Median percentage change in antibody titers from three to six months was −29.4%. The only factor significantly associated with the percentage change in Ab titers was not age or smoking, but sex (women, −31.6%; men, −25.1%). Conclusion: The most important factors associated with lower antibody titers at six months were age and smoking, as at three months, probably reflecting their effect on peak antibody titers. However, the only factor significantly associated with the attenuation in Ab titers from three to six months was sex, which reduced the sex difference seen during the first three months. Antibody titers may be affected by different factors at different time points.

Immunogenicity after 6 months of BNT162b2 vaccination in frail or disabled nursing home residents: The COVID-A Study.

There is incomplete information regarding evolution of antibody titers against SARS-CoV-2 after a two-dose strategy vaccination with BNT162b2 in older adults in long-term care facilities (LTCFs) with frailty, disability, or cognitive impairment. We aimed to determine IgG antibody titer loss in older adults in LTCFs. This is a multicenter longitudinal cohort study including 127 residents (90 females and 37 males) with a mean age of 82.7 years (range 65-99) with different frailty and disability profiles in two LTCFs in Albacete, Spain. Residents received two doses of BNT162b2 as per label, and antibody levels were determined 1 and 6months after the second dose. Age, sex, previous history of coronavirus disease 2019 (COVID-19), comorbidity (Charlson Index), performance in activities of daily living (Barthel Index), frailty (FRAIL instrument), and cognitive status were assessed. The mean antibody titers 1 and 6months after the second vaccine dose were 32,145 AU/ml (SD 41,206) and 6182 AU/ml (SD 13,316), respectively. Across all participants, the median antibody titer loss measured 77.6% (interquartile range [IQR] 23.8%). Notably, the decline of titers in individuals with pre-vaccination COVID-19 infection was significantly lower than in those without a history of SARS-CoV-2 infection (72.2% vs. 85.3%; p < 0.001). The median titer decrease per follow-up day was 0.47% (IQR 0.14%) and only pre-vaccination COVID-19 was associated with lower rate of antibody decline at 6months (hazard ratio 0.17; 95% confidence interval 0.07-0.41; p < 0.001). Frailty, disability, older age, cognitive impairment, or comorbidity were not associated with the extent of antibody loss. Older adults in LTCFs experience a rapid loss of antibodies over the first 6 months after the second dose of BNT162b2 vaccine. Only pre-vaccination COVID-19 is associated with a slower rate of antibody decrease. Our data support immunization with a third dose in this vulnerable, high-risk population.

462. Differences in the Humoral Response to SARS-CoV-2 Infection in Children vs. Adult

BackgroundOne of the most striking observations of the COVID-19 pandemic has been the difference in infection among children vs. adults. Overall, children with SARS-CoV-2 infection generally had milder disease compared to adults, though the cause is not clear. The objective of this study was to compare the humoral response to infection in children vs. adults of a same family.MethodsWe performed a prospective cohort study at Sainte-Justine University Health Center in Montreal, Canada from July 2020 to March 2021. Children with a positive SARS-CoV-2 PCR were recruited from the COVID-19 clinic (index case), enrollment was offered to all household members. Serum IgG against SARS-CoV-2 native S1/S2 spike proteins was measured using the Diasorin (Liaison XL) assay, 4-6 months following a positive PCR. A mean antibody threshold of 15 Arbitrary unit per ml (AU/ml) was considered seropositive, with 94.4% positive agreement to plaque reduction neutralization tests (PRNT90) at a 1:40 ratio. Antibody titer was compared between children and adults.Results111 participants (52 adults and 59 children) were recruited from 50 separate families. Characteristic of participants and their clinical symptoms are described in Table 1. Among all participants, 76.3% children were SARS-CoV-2 seropositive vs. 51.9% of adults (p=0.007). Median antibody titer was significantly higher in children vs. adults (82.8 AU, [IQR: 18.4-130], vs 17.0 AU, [IQR: 6.8-77.8], p=0.006); findings were similar among SARS-CoV-2 PCR positive participants only. Overall, 13 participants were PCR positive but seronegative, 7 were PCR negative and seropositive, while 61 were both PCR positive and seropositive. Older participants and those with any comorbidity. Among the PCR positive group, the seropositive participants were younger (median age 31±17 vs 19±17 years, p=0.003) and more likely to have comorbidity (69% vs 29%, p=0.007). ConclusionThese results suggest that children have a stronger antibody response to SARS-CoV-2 infection than adults, and that older age and presence of comorbidity are associated with a less robust humoral response. Further work on the differences in response between children and adults may help elucidate mechanisms underlying the severity of diseaseDisclosures Olivier Drouin, MDCM MsC MPH, Covis Pharma (Research Grant or Support)

Achieving High Immunogenicity Against Poliovirus With Fractional Doses of Inactivated Poliovirus Vaccine in Ecuador

Background: In January 2018, Ecuador changed its routine immunization schedule by replacing one full dose of inactivated poliovirus vaccine (IPV) administered intramuscularly at 2 months of age with two doses of fractional IPV (1/5th of full dose, fIPV) administered intradermally at 2 and 4 months of age; bivalent oral poliovirus vaccine (serotypes 1 and 3, bOPV) continues to be used. We compared seroprevalence and titers of polio antibodies achieved by the past and the current immunization schedules. Methods: This was a cross-sectional serological survey in children in Ecuador who received bOPV and either one IPV dose in 2017 or two fIPV doses in 2018. One blood sample was collected between October 2020 and March 2021 and analysed for presence of poliovirus neutralizing antibodies at CDC, Atlanta by microneutralization assay. Findings: We obtained 321 analyzable samples from 329 (97·6%) enrolled children (160 received IPV and 161 fIPV). For serotype 2, seroprevalence was 50.0% (CI95%= 44·2-55·8%) for IPV and 83·2% (CI95%=78·5-87·1%) for fIPV recipients (p<0·001). Median antibody titers for serotype 2 were significantly lower for IPV than for fIPV recipients (3·0, CI95%= 3 – 3·5 vs. 4·8, CI95%= 4·5 – 5·2, p<0·001). Seroprevalence for serotypes 1 and 3 was above 90% and was not significantly different between IPV and fIPV recipients. Interpretation: Ecuador achieved significantly better poliovirus serotype 2 immunogenicity with two fIPV doses than with one IPV dose, while preserving vaccine supply and reducing costs. Our data provide further evidence that fIPV is a beneficial and cost-effective option in polio immunization. Funding Information: The World Health Organization to the University of San Francisco. Declaration of Interests: All authors – no conflict of interest declared. Ethics Approval Statement: The protocol was reviewed and approved by the Human Research Ethics Committee - CEISH-USFQ and by the Ethics Review Committee at the WHO in Geneva. After obtaining informed consent the children were enrolled.

Response to BNT162b2 Sars-Cov-2 Vaccine in Recipients of Allogeneic Hematopoietic Stem Cell Transplant

Recipients of allogeneic hematopoietic stem cell transplant (HSCT) have been excluded from clinical trials of SARS-CoV-2 messenger RNA (mRNA) vaccines; however, since these patients are at higher risk of severe complications following infection, they have been given high priority in vaccination campaigns worldwide. In this prospective observational study, we evaluated the immunogenicity of two BNT162b2 (Pfizer-BioNTech) vaccine doses in allogeneic HSCT recipients compared to healthy controls. IgG antibodies to the receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2 were analyzed by SARS-CoV-2 IgG II Quant (Abbott, Ireland). The cutoff value of the test used in this study is 7.1 BAU/mL (Binding Antibody Unit/mL) and the results greater than 7.1 indicate that seroconversion has occurred, as recommended by the manufacturer. Peripheral blood samples were collected for immunological analysis at three timepoints: pre-vaccine baseline (w0, before the first BNT162b2 dose), week 3 (w3, before the second vaccine dose) and week 5 (w5, 2 weeks following the second dose). Patients older than 18 years who received BNT162b2 vaccine following an HSCT at seven Italian centers were included in the study. Enrolled patients received two successive doses (at 3-week interval) at a median of 15 months (range 2-141) after HSCT. Twenty-nine age-matched health care workers who were vaccinated with BNT162b2 were recruited as the control group. Among the 34 patients evaluable for serological response, three patients were excluded from the analysis as the baseline serology demonstrated previous natural SARS-CoV-2 infection. On w3, after the first vaccine dose 7/31 (23%) patients developed anti-S IgG antibodies as compared to 28/29 (97%) controls (p<0.01). HSCT recipients showed lower antibody titers (median 1.8 BAU, range 0-481) as compared to healthy controls (median 118 BAU, range 6-1172, p<0.01). In univariate analysis, transplant-to-vaccination interval (>12 months, p<0.01), baseline CD4+ T cell count (>200/mm3, p=0.01), and CD4+CD45RA+ T naive cell count (>100/ mm3, p<0.01) were significantly associated with antibody response after the first vaccine dose. On w5, after the second vaccine dose, 24/31 (77%) of the patients showed antibody response, as compared to 99% of healthy controls (p<0.01); in fact, 71% of non-responders to the first dose developed IgG antibodies after vaccine boost (Figure 1). Median antibody titer after second dose was 350 BAU/ml (0-21.731). In univariate analysis, no significant association was found between patient characteristics and immunogenicity after vaccine boost. Adverse events were rare and modest. Nine percent of the patients reported mild local reactions after vaccine administration, including pain at the injection site and less commonly local erythema, local lymphadenopathy, or swelling; 35% of patients reported systemic adverse events, and all were mild. The most frequently reported systemic reactions included weakness (15%), headache (9%), and diarrhea (3%). In conclusion, in recipients of HSCT, a single dose of the BNT162b2 SARS-CoV-2 vaccine yielded poor efficacy, while immunogenicity increased significantly after vaccine boost at day 21 after the first dose. Patients who received vaccines beyond one year after transplant were more likely to mount anti-S IgG antibodies, which could be due to a broader immune reconstitution, as we observed an enhanced response to single BNT162b2 vaccine dose in patients with higher CD4+ T cell and particularly CD4+CD45RA+ naïve T cell counts. [Display omitted] DisclosuresKordasti: Alexion: Honoraria; Celgene: Research Funding; Beckman Coulter: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Pane: AbbVie; Amgen; Novartis: Other: Travel, accommodation, expenses; AbbVie; Amgen; Novartis, GSK, Incyte: Speakers Bureau; Novartis Pharma SAS;: Research Funding; AbbVie; Amgen; Novartis, GSK , Incyte: Consultancy.

High Humoral Response after Anti-Sars-Cov-2 mRNA-Based Vaccines in Patients with Active Multiple Myeloma (MM) and Relationship with Disease Status/Line of Therapy

High Humoral Response after Anti-Sars-Cov-2 mRNA-Based Vaccines in Patients with Active Multiple Myeloma (MM) and Relationship with Disease Status/Line of Therapy