Antibody Decay Research Articles

Quantification of Severe Acute Respiratory Syndrome Coronavirus 2 Binding Antibody Levels To Assess Infection and Vaccine-Induced Immunity Using WHO Standards.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binding antibody (Ab) levels following vaccination or natural infection could be used as a surrogate for immune protection if results of serological assays were standardized to yield quantitative results using an international standard. Using a bead-based serological assay (Luminex xMAP), anti-receptor binding domain (anti-RBD) Ab levels were determined for 1,450 participants enrolled in the Los Angeles Pandemic Surveillance Cohort (LAPSC) study. For 123 participants, SARS-CoV-2 binding antibody unit (BAU) levels were also quantified using WHO standards and then compared to the semiquantitative results. Samples were chosen to represent the range of results and time from vaccination. Antibody levels and decay rates were then compared using unadjusted and adjusted linear regression models. The linear range of the assay used in this study was determined to be 300 to 5,000 mean fluorescence intensity units (MFI). Among the fully vaccinated groups (vaccinated only and vaccinated with past infection), 84.8% had anti-RBD MFI values above the linear range of >5,000 MFI, and 33.8% had values of >15,000 MFI. Among vaccinated participants with past infection (hybrid immunity), 97% had anti-RBD values of >5,000 MFI and 70% (120/171) had anti-RBD values of >15,000 MFI. In the subgroup quantified using the WHO control, BAU levels were significantly higher than the semiquantitative MFI results. In vaccinated participants, Ab decay levels were similar between infected and noninfected groups (P = 0.337). These results demonstrate that accurate quantitation is possible if standardized with an international standard. BAU can then be compared over time or between subjects and would be useful in clinical decision making. IMPORTANCE Accurate quantification of SARS-CoV-2-specific antibodies can be achieved using a universal standard with sample dilution within the linear range. With hybrid immunity being now common, it is critical to use protocols adapted to high Ab levels to standardize serological results. We validated this approach with the Los Angeles Pandemic Surveillance Cohort by comparing the antibody decay rates in vaccinated participants and vaccinated infected participants.

Effects of two supplements on rate of infectious bursal disease virus antibody decay and response to a very virulent strain of the virus in pullet chicks

This study evaluated the effects of two supplements on the rate of infectious bursal disease virus (IBDV) antibody decay and response to a very virulent strain of the virus (vvIBDV) in pullet chicks. Two hundred ISA Brown 1-day-old chicks were divided into four groups (AD), each containing 50 birds. Chicks in group A were given supplement A, and B supplement B, from 1-day-old to 42 days of age, while C (positive control) and D (negative control) were not given any supplement. Groups A, B and C were challenged with vvIBDV at 28-days-old. Blood was collected from each bird, serum was obtained and analysed for antibodies against IBDV. The rate of antibody decay and response to vvIBDV were determined. There was significantly higher (p<0.05) antibody titre in chicks of groups A and B than in C and D at days 28, 35 and 42. The rate of antibody decay was lower in chicks of groups A (-57.7%) and B (-65.4%) than in C (-72.1%) and D (-74.2%) at 28-days-old. The antibody response rate was higher in groups A (+76.4%) and B (+71.1%) at 35-days-old. There was lower antibody decline rate in groups A (-22.4%) and B (-29.0%) compared to C (-38.6%) and D (-51.4%) at 42-days-old. These supplements decreased IBD antibody decay, enhanced antibody response to vvIBDV infection and decreased antibody decline by vvIBDV. Therefore, the use of these supplements in IBD outbreaks to enhance immune responses is recommended.

Efficacy of different live infectious bursal disease vaccines on antibodies to infectious bursal disease virus and Newcastle disease vaccine La Sota in ISA brown chicks

Aim: In this study, the efficacy of five commercial live infectious bursal disease (IBD) vaccines on antibody (Ab) decay and response to a very virulent IBD virus (vvIBDV) and Newcastle disease (ND) vaccine La Sota in ISA Brown chicks were assessed. Methods: Seven groups of chickens (A, B, C, D, E, F, and G) comprising 50 chicks each were used for the study. Groups A, B, C, D, and E were vaccinated with Bur-706, MB-Strain, B87-Strain, Bursa-B2K, and HIPRA live IBD vaccines, respectively, at 14 and 28 days of age (doa), and challenged with a vvIBDV at 35 doa. Groups F and G served as positive and negative controls, respectively. At 42 doa, all groups were vaccinated with ND vaccine La Sota. Blood was collected at 1, 7, 14, 21, 28, 35, 42, and 49 doa, and serum was harvested. The serum was analyzed for IBD virus (IBDV) Ab titres using enzyme-linked immunosorbent assay (ELISA) and ND Ab titres using a haemagglutination inhibition (HI) test. Results: Results revealed significantly (p < 0.05) higher ELISA IBDV Ab titres in groups A to E than in F from 21 to 49 doa, with the highest in group D. At 49 doa, there was significantly (p < 0.05) higher HI Ab titre in groups A to E than in F with the highest in group D. In conclusion, the live IBDV vaccines were immunogenic following vaccination. The vaccines decreased the decay of IBDV Ab and mitigated the decreased response to ND vaccine La Sota in the chicks following the vvIBDV challenge, with more effects induced by Bursa-B2K. Conclusion: The live vaccines (Bur-706, MB-Strain, B87-Strain, Bursa-B2K, and HIPRA) were immunogenic following vaccination.

1163. Age, Poverty and Inequity are Key Determinants of Dengue Severity in Colombia

Abstract Background Age has been a major risk factor for death and complication due to dengue infection (DENV). Although antibody-dependent enhancement (ADE) has been proposed as an explanation, other variables could shape disease outcomes. We aimed to analyze the role of age as a risk factor for disease severity across departments (first administrative level), and epidemic years in Colombia considering poverty and inequity indexes. Methods We conducted a retrospective study analyzing DENV epidemiological data from Colombia between 2012 to 2017, and monetary poverty, extreme poverty, and GINI indexes. Total cases, incidence, incidence of severe DENV, mortality, case- fatality rates (CFR), and complication rates (CR) were calculated for each department and year. The effect of age, department, year of infection, monetary poverty, extreme poverty, and GINI on CR and CFR was evaluated by using a generalized additive model. Results After adjustment, age (p< 0.001), GINI (p< 0.001), monetary poverty (p< 0.001), and extreme poverty(p< 0.001) indexes were significantly associated with the CR, but age was the only variable significantly associated with CFR (p< 0.001). Our results revealed a first peak of CR in patients younger than 5 years old, the second peak in patients between 27 to 34 years old, and a third peak after 45 years old. Conclusion Our work has important implications for future designing of human cohorts analyzing the risk of complications in adults and provides evidence for improving clinical DENV risk assessment. Our findings are consistent with similar observations linking ADE with severe DENV in childhood and suggest protective antibody decay during adulthood. The interplay of biological and socioeconomic factors shaping clinical outcomes in DENV is complex and should be further analyzed Disclosures All Authors: No reported disclosures.

Anti-SARS-CoV-2 inactivated vaccine in patients with ANCA-associated vasculitis: Immunogenicity, safety, antibody decay and the booster dose

ObjectiveTo evaluate inactivated CoronaVac prime vaccination, antibody decay, booster dose, and safety in ANCA-Associated Vasculitis (AAV) patients. MethodsFifty-three AAV patients and 106 Controls (CG) received CoronaVac on days: D0 (first dose), D28(second dose), and D210 (booster dose, 32 AAV: 32 CG). The primary outcome was immunogenicity after the second vaccine dose (day 69) assessed by Seroconversion Rates (SC) of anti-SARS-CoV-2 S1/S2 IgG and Neutralizing Antibodies (NAb). Secondary outcomes were safety, immunogenicity (D28/D240), 6-months antibody decay (D210) and the booster dose response (D240). ResultsAt D69 SC (65.1% vs. 96.8%, p = 0.0001), GMT (21.3 UA/mL vs. 67.7 UA/mL, p < 0.001) and NAb- positivity (53.7% vs. 80.6%, p = 0.001) were moderate but lower in naïve-AAV patients than CG. Patients without SC used more often IS (93.3% vs. 53.3%, p = 0.015), mycophenolate mofetil (20% vs. 0%, p = 0.037) and prednisone (60.0% vs. 28.6%, p = 0.057) than seroconverted. NAb negativity in AAV patients was associated with prednisone treatment (57.9% vs. 18.2%, p = 0.015) and IS (84.2% vs. 55.0%, p = 0.046). Logistic regression analysis models showed that only prednisone was associated with lower seroconversion (OR = 0.2, 0,95% CI 0.05‒0.86, p = 0.030) and with lower NAb positivity (OR = 0.2, 0,95% CI 0.05‒0.88, p = 0.034). After six months (D69‒D210) a decrease in IgG positivity occurred in 32 AAV patients (15.7%, p = 0.074) and 32 CG (18.7%, p = 0.041). For the NAb positivity, the 6-month decrease was not significant (p = 0.114) whereas a major reduction occurred for CG (p < 0.001). A booster dose (D240) resulted in an increment in IgG-positivity (21.9%, p = 0.023) and NAb-positivity (34.4%, p = 0.006) in AAV patients. No moderate/severe adverse events attributable to the vaccine were observed. ConclusionThis study provides novel data on the excellent safety and moderate immunogenicity of CoronaVac in AAV patients. A six-month mild antibody waning was observed with a good response to the booster dose, although levels remained lower than CG (CoronavRheum-NCT04754698).

Nationally representative results on SARS-CoV-2 seroprevalence and testing in Germany at the end of 2020

Pre-vaccine SARS-CoV-2 seroprevalence data from Germany are scarce outside hotspots, and socioeconomic disparities remained largely unexplored. The nationwide representative RKI-SOEP study (15,122 participants, 18–99 years, 54% women) investigated seroprevalence and testing in a supplementary wave of the Socio-Economic-Panel conducted predominantly in October–November 2020. Self-collected oral-nasal swabs were PCR-positive in 0.4% and Euroimmun anti-SARS-CoV-2-S1-IgG ELISA from dry-capillary-blood antibody-positive in 1.3% (95% CI 0.9–1.7%, population-weighted, corrected for sensitivity = 0.811, specificity = 0.997). Seroprevalence was 1.7% (95% CI 1.2–2.3%) when additionally correcting for antibody decay. Overall infection prevalence including self-reports was 2.1%. We estimate 45% (95% CI 21–60%) undetected cases and lower detection in socioeconomically deprived districts. Prior SARS-CoV-2 testing was reported by 18% from the lower educational group vs. 25% and 26% from the medium and high educational group (p < 0.001, global test over three categories). Symptom-triggered test frequency was similar across educational groups. Routine testing was more common in low-educated adults, whereas travel-related testing and testing after contact with infected persons was more common in highly educated groups. This countrywide very low pre-vaccine seroprevalence in Germany at the end of 2020 can serve to evaluate the containment strategy. Our findings on social disparities indicate improvement potential in pandemic planning for people in socially disadvantaged circumstances.

Antibody response and intra-host viral evolution after plasma therapy in COVID-19 patients pre-exposed or not to B-cell-depleting agents.

SummaryAdministration of plasma therapy may contribute to viral control and survival of COVID‐19 patients receiving B‐cell‐depleting agents that impair humoral immunity. However, little is known on the impact of anti‐CD20 pre‐exposition on the kinetics of SARS‐CoV‐2‐specific antibodies. Here, we evaluated the relationship between anti‐spike immunoglobulin G (IgG) kinetics and the clinical status or intra‐host viral evolution after plasma therapy in 36 eligible hospitalized COVID‐19 patients, pre‐exposed or not to B‐cell‐depleting treatments. The majority of anti‐CD20 pre‐exposed patients (14/17) showed progressive declines of anti‐spike IgG titres following plasma therapy, contrasting with the 4/19 patients who had not received B‐cell‐depleting agents (p = 0.0006). Patients with antibody decay also depicted prolonged clinical symptoms according to the World Health Organization (WHO) severity classification (p = 0.0267) and SARS‐CoV‐2 viral loads (p = 0.0032) before complete virus clearance. Moreover, they had higher mutation rates than patients able to mount an endogenous humoral response (p = 0.015), including three patients with one to four spike mutations, potentially associated with immune escape. No relevant differences were observed between patients treated with plasma from convalescent and/or mRNA‐vaccinated donors. Our study emphasizes the need for an individualized clinical care and follow‐up in the management of COVID‐19 patients with B‐cell lymphopenia.

Induction, decay, and determinants of functional antibodies following vaccination with the RTS,S malaria vaccine in young children

BackgroundRTS,S is the first malaria vaccine recommended for implementation among young children at risk. However, vaccine efficacy is modest and short-lived. Antibodies play the major role in vaccine-induced immunity, but knowledge on the induction, decay, and determinants of antibody function is limited, especially among children. Antibodies that promote opsonic phagocytosis and other cellular functions appear to be important contributors to RTS,S immunity.MethodsWe studied a phase IIb trial of RTS,S/AS02 conducted in young children in malaria-endemic regions of Mozambique. We evaluated the induction of antibodies targeting the circumsporozoite protein (CSP, vaccine antigen) that interact with Fcγ-receptors (FcRγs) and promote phagocytosis (neutrophils, monocytes, THP-1 cells), antibody-dependent respiratory burst (ADRB) by neutrophils, and natural killer (NK) cell activity, as well as the temporal kinetics of responses over 5 years of follow-up (ClinicalTrials.gov registry number NCT00197041).ResultsRTS,S vaccination induced CSP-specific IgG with FcγRIIa and FcγRIII binding activity and promoted phagocytosis by neutrophils, THP-1 monocytes, and primary human monocytes, neutrophil ADRB activity, and NK cell activation. Responses were highly heterogenous among children, and the magnitude of neutrophil phagocytosis by antibodies was relatively modest, which may reflect modest vaccine efficacy. Induction of functional antibodies was lower among children with higher malaria exposure. Functional antibody magnitude and the functional activity of antibodies largely declined within a year post-vaccination, and decay were highest in the first 6 months, consistent with the decline in vaccine efficacy over that time. Decay rates varied for different antibody parameters and decay was slower for neutrophil phagocytosis. Biostatistical modelling suggested IgG1 and IgG3 contribute in promoting FcγR binding and phagocytosis, and IgG targeting the NANP-repeat and C-terminal regions CSP were similarly important for functional activities.ConclusionsResults provide new insights to understand the modest and time-limited efficacy of RTS,S in children and the induction of antibody functional activities. Improving the induction and maintenance of antibodies that promote phagocytosis and cellular functions, and combating the negative effect of malaria exposure on vaccine responses are potential strategies for improving RTS,S efficacy and longevity.

Two-year Decay of Zika Virus Neutralizing Antibodies in People Living in an Endemic Region in Brazil.

It is currently not clear whether humoral immunity to Zika virus (ZIKV) elicited upon natural ZIKV infection is long-lasting. In addition, cross-reactivity of anti-ZIKV antibodies with antigenically related dengue viruses (DENV) may have biological implications in nonnaive individuals who subsequently acquire a heterotypic infection. Cross-reactive humoral immunity between ZIKV and DENV also complicates the interpretation of serological tests to evaluate previous exposure to either virus. Here, we have measured the 2-year decay of ZIKV neutralizing antibodies in people living in a ZIKV/DENV endemic area in Brazil who were identified as having an acute infection (group 1) or past (but recent) infection (group 2) with ZIKV in 2015-16. The titers of neutralizing antibodies to ZIKV decreased 9.1 and 2.3 times in groups 1 and 2, respectively. We also show that the plaque reduction neutralization assay (PRNT) is a reliable method to measure past exposure to ZIKV in coendemic areas.

Field Investigation of Infectious Bursal Disease Maternal Antibody Transfer and Decay Rates in Selected Chicken Breeder Flocks and Progeny

Field Investigation of Infectious Bursal Disease Maternal Antibody Transfer and Decay Rates in Selected Chicken Breeder Flocks and Progeny

Estimating typhoid incidence from community-based serosurveys: a multicohort study

SummaryBackgroundThe incidence of enteric fever, an invasive bacterial infection caused by typhoidal Salmonellae (Salmonella enterica serovars Typhi and Paratyphi), is largely unknown in regions without blood culture surveillance. The aim of this study was to evaluate whether new diagnostic serological markers for typhoidal Salmonella can reliably estimate population-level incidence.MethodsWe collected longitudinal blood samples from patients with blood culture-confirmed enteric fever enrolled from surveillance studies in Bangladesh, Nepal, Pakistan, and Ghana between 2016 and 2021 and conducted cross-sectional serosurveys in the catchment areas of each surveillance site. We used ELISAs to measure quantitative IgA and IgG antibody responses to hemolysin E and S Typhi lipopolysaccharide. We used Bayesian hierarchical models to fit two-phase power-function decay models to the longitudinal antibody responses among enteric fever cases and used the joint distributions of the peak antibody titres and decay rate to estimate population-level incidence rates from cross-sectional serosurveys.FindingsThe longitudinal antibody kinetics for all antigen-isotypes were similar across countries and did not vary by clinical severity. The seroincidence of typhoidal Salmonella infection among children younger than 5 years ranged between 58·5 per 100 person-years (95% CI 42·1–81·4) in Dhaka, Bangladesh, to 6·6 per 100 person-years (4·3–9·9) in Kavrepalanchok, Nepal, and followed the same rank order as clinical incidence estimates.InterpretationThe approach described here has the potential to expand the geographical scope of typhoidal Salmonella surveillance and generate incidence estimates that are comparable across geographical regions and time.FundingBill & Melinda Gates Foundation.TranslationsFor the Nepali, Bengali and Urdu translations of the abstract see Supplementary Materials section.

Decay of anti-Bordetella pertussis antibodies in women of childbearing age following COVID-19 non-pharmaceutical measures

BackgroundImmunization against Bordetella pertussis during pregnancy reduces morbidity from severe pertussis in young infants via trans-placental transfer of anti-B. pertussis Immunoglobulin G (IgG). Studies have reported a near disappearance of respiratory pathogens including B. pertussis following implementation of mitigation strategies to control Coronavirus disease 2019 (COVID-19). We explored how immunity against B. pertussis changed in women of childbearing-age through the COVID-19 pandemic. MethodsPaired blood samples from females of childbearing-age collected at the beginning (May-June 2020) and nearly one year into the COVID-19 pandemic (February-May 2021) in British Columbia (BC), Canada were tested for anti-B. pertussis IgG levels. To ascertain whether early-pandemic IgG levels in 2020 reflected levels in pregnant women early in gestation, 1st trimester sera collected from age-matched healthy pregnant women in 2018 and 2019 were tested for anti-B. pertussis IgG. Levels were compared by t tests. P-value of 0.05 was assigned and statistical significance was set as p < 0.016 using Bonferroni correction. ResultsAnnual provincial B. pertussis incidences per 100,000 in BC in 2020 (3/100,000) and 2021 (<1/100,000) approximated the lowest levels since 1990. In 2021 vs. 2020, anti-pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) IgG levels declined in women of childbearing-age: 6.8 IU/ml (95 %CI, 4.2–10.9) vs. 8.4 IU/ml (5.1–13.9; p = 0.004); 18.8 IU/ml (10.9–32.2) vs. 23.6 IU/ml (13.2–42.1; p < 0.001); and 37.1 IU/ml (18.1–75.9) vs. 47.2 IU/ml (24.8–89.9; p = 0.092), respectively. Although all values were slightly higher, anti-PT, FHA and PRN IgG levels in women of childbearing age did not significantly differ in 2020 compared with early-gestation pregnant women in 2018–2019, 8.4 IU/ml (95% CI, 5.1–13.9) vs. 5.4 IU/ml (95% CI, 3.8–7.7; p = 0.166), 23.6 IU/ml (95% CI, 13.2–42.1) vs. 20.1 IU/ml (95% CI, 13.4–30.2; p = 0.656), and 47.2 IU/ml (24.8–89.9) vs. 17.3 IU/ml (95% CI, 10.5–28.7; p = 0.021), respectively. DiscussionB. pertussis infections should be closely monitored during the relaxing of mitigation measures for COVID-19.

B cell receptor repertoire dynamics and convergent evolution following SARS-CoV-2 vaccination

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel betacoronavirus causing Coronavirus disease 2019 (COVID-19). B cell receptors (BCRs) are expressed at the surface of the B cell and are secreted as soluble antibodies. These antibodies can block viral infection by neutralizing the virus, are critical for resolution of SARS-CoV-2 infection, and may be correlates of protection for COVID-19 vaccines. We have previously shown that SARS-CoV-2 immunization elicits a robust antibody response that is significantly higher in individuals who recovered from COVID-19. Moreover, recovered individuals had slower antibody decay in their levels seven months after vaccination. Here, we sequenced the BCR repertoire of individuals undergoing vaccination by SARS-CoV-2 mRNA vaccine (Pfizer, BNT162b2) with (seropositive) or without (seronegative) previous laboratory confirmed COVID-19 infection. We identified genetic differences in the BCR repertoire between groups including V gene usage, CD3R length, percentage of somatic hypermutation, and clonotype diversity. We then focused our analyses to vaccine-expanded clonotypes in both groups to further analyze the differences in BCR repertoire on candidate SARS-CoV-2-specific clonotypes. We determined the frequency of pre-existing clones present after infection that were engaged by the vaccine in the seropositive group. Moreover, in both groups we identified clonotypes that were shared among individuals that could be a result of convergent evolution. Defining the characteristics and evolution of the BCR repertoire during vaccination of individuals with different histories of viral infection will aid in understanding SARS-CoV-2 humoral response dynamics.

A Third Dose of an Inactivated Vaccine Dramatically Increased the Levels and Decay Times of Anti-SARS-CoV-2 Antibodies, but Disappointingly Declined Again: A Prospective, Longitudinal, Cohort Study at 18 Serial Time Points Over 368 Days

BackgroundDue to anti-SARS-CoV-2 antibody decay and SARS-CoV-2 variants, vaccine booster doses are a constant concern. It was focused on whether the third dose can quickly evoke and activate immunity and produce a sufficient and durable immune protection.ObjectivesTo evaluate the responses and durations of five subsets of anti-SARS-CoV-2 antibodies and their predictive values for protection after the administration of a three-dose inactivated SARS-CoV-2 vaccines regimens.MethodsA prospective cohort study of five subsets of anti-SARS-CoV-2 antibodies (neutralizing antibody, anti-RBD total antibody, anti-Spike IgG, anti-Spike IgM, and anti-Spike IgA) was carried out to evaluate the efficacies and immune characteristics of a three-dose inactivated SARS-CoV-2 vaccines regimen in 32 volunteers. The dynamic response and immune decay were longitudinally profiled at 18 serial time points over 368 days.ResultsThe neutralizing antibody, anti-RBD total antibody, anti-Spike IgG and anti-Spike IgA levels rapidly increased to 773.60 (380.90-1273.00) IU/mL, 639.30 (399.60-878.60) AU/mL, 34.48 (16.83-44.68) S/CO and 0.91 (0.35-1.14) S/CO, respectively, after the administration of the third dose. Compared to the peak value after the second dose, these values were increased by 4.22-fold, 3.71-fold, 1.01-fold and 0.92-fold. On the other hand, the half-lives of the neutralizing antibody, anti-RBD total antibody, and anti-Spike IgG were 56.26 (95% CI, 46.81 to 70.49) days, 66.37 (95% CI, 54.90 to 83.88) days, and 82.91 (95% CI, 63.65 to 118.89) days, respectively. Compared to the half-lives after the second dose, these values were increased by 1.71-fold, 2.00-fold, and 2.93-fold, respectively. Nevertheless, the positive conversion rate of anti-Spike IgM was decreased to 9.38% (3/32), which was much lower than that after the second dose (65.63% (21/32)).ConclusionsCompared to the second dose, the third dose dramatically increased the antibody levels and decay times. However, the half-life of neutralizing antibody remained unsatisfactory. Due to decay, a fourth dose, and even annual revaccination, might be considered in the SARS-CoV-2 vaccination management strategy.

Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine

We examined antibody and memory B cell responses longitudinally for ∼9–10 months after primary 2-dose SARS-CoV-2 mRNA vaccination and 3 months after a 3rd dose. Antibody decay stabilized between 6 and 9 months, and antibody quality continued to improve for at least 9 months after 2-dose vaccination. Spike- and RBD-specific memory B cells remained durable over time, and 40%–50% of RBD-specific memory B cells simultaneously bound the Alpha, Beta, Delta, and Omicron variants. Omicron-binding memory B cells were efficiently reactivated by a 3rd dose of wild-type vaccine and correlated with the corresponding increase in neutralizing antibody titers. In contrast, pre-3rd dose antibody titers inversely correlated with the fold-change of antibody boosting, suggesting that high levels of circulating antibodies may limit the added protection afforded by repeat short interval boosting. These data provide insight into the quantity and quality of mRNA-vaccine-induced immunity over time through 3 or more antigen exposures.

Biphasic Waning of Hemagglutination Inhibition Antibody Titers After Influenza Vaccination in Children.

We explored the potential for a biphasic pattern in waning of antibody titers after influenza vaccination. We collected blood samples in a randomized controlled trial of influenza vaccination in children and tested them with hemagglutination inhibition assays for influenza A(H3N2) and influenza B/Victoria lineage. Using piecewise log-linear mixed-effects models, we found evidence for a faster initial waning of antibody titers for the first 1-2 years after vaccination and then slower longer-term declines. Children with higher postvaccination titers had faster antibody decay.

Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab

Anti tumour necrosis factor (anti-TNF) drugs increase the risk of serious respiratory infection and impair protective immunity following pneumococcal and influenza vaccination. Here we report SARS-CoV-2 vaccine-induced immune responses and breakthrough infections in patients with inflammatory bowel disease, who are treated either with the anti-TNF antibody, infliximab, or with vedolizumab targeting a gut-specific anti-integrin that does not impair systemic immunity. Geometric mean [SD] anti-S RBD antibody concentrations are lower and half-lives shorter in patients treated with infliximab than vedolizumab, following two doses of BNT162b2 (566.7 U/mL [6.2] vs 4555.3 U/mL [5.4], p <0.0001; 26.8 days [95% CI 26.2 – 27.5] vs 47.6 days [45.5 – 49.8], p <0.0001); similar results are also observed with ChAdOx1 nCoV-19 vaccination (184.7 U/mL [5.0] vs 784.0 U/mL [3.5], p <0.0001; 35.9 days [34.9 – 36.8] vs 58.0 days [55.0 – 61.3], p value < 0.0001). One fifth of patients fail to mount a T cell response in both treatment groups. Breakthrough SARS-CoV-2 infections are more frequent (5.8% (201/3441) vs 3.9% (66/1682), p = 0.0039) in patients treated with infliximab than vedolizumab, and the risk of breakthrough SARS-CoV-2 infection is predicted by peak anti-S RBD antibody concentration after two vaccine doses. Irrespective of the treatments, higher, more sustained antibody levels are observed in patients with a history of SARS-CoV-2 infection prior to vaccination. Our results thus suggest that adapted vaccination schedules may be required to induce immunity in at-risk, anti-TNF-treated patients.

Associations Between Symptoms, Donor Characteristics and IgG Antibody Response in 2082 COVID-19 Convalescent Plasma Donors

Many studies already reported on the association between patient characteristics on the severity of COVID-19 disease outcome, but the relation with SARS-CoV-2 antibody levels is less clear. To investigate this in more detail, we performed a retrospective observational study in which we used the IgG antibody response from 11,118 longitudinal antibody measurements of 2,082 unique COVID convalescent plasma donors. COVID-19 symptoms and donor characteristics were obtained by a questionnaire. Antibody responses were modelled using a linear mixed-effects model. Our study confirms that the SARS-CoV-2 antibody response is associated with patient characteristics like body mass index and age. Antibody decay was faster in male than in female donors (average half-life of 62 versus 72 days). Most interestingly, we also found that three symptoms (headache, anosmia, nasal cold) were associated with lower peak IgG, while six other symptoms (dry cough, fatigue, diarrhoea, fever, dyspnoea, muscle weakness) were associated with higher IgG concentrations.

Persistence of SARS-CoV-2 total immunoglobulins in a series of convalescent plasma and blood donors.

BackgroundThe vast majority of COVID-19 cases both symptomatic and asymptomatic develop immunity after COVID-19 contagion. Whether lasting differences exist between infection and vaccination boosted immunity is yet to be known. The aim of this study was to determine how long total anti-SARS-CoV2 antibodies due to past infection persist in peripheral blood and whether sex, age or haematological features can influence their lasting.Material and methodsA series of 2421 donations either of SARS-CoV-2 convalescent plasma or whole blood from 1107 repeat donors from January 2020 to March 2021 was analysed. An automated chemiluminescence immunoassay for total antibodies recognizing the nucleocapsid protein of SARS-CoV-2 in human serum and plasma was performed. Sex, age, blood group, blood cell counts and percentages and immunoglobulin concentrations were extracted from electronic recordings. Blood donation is allowed after a minimum of one-month post symptom’s relapse. Donors were 69.7% males and their average age was 46. The 250 donors who had later donations after a positive one underwent further analysis. Both qualitative (positivity) and quantitative (rise or decline of optical density regarding consecutive donations) outcomes were evaluated.Results and discussionIn 97.6% of donors with follow-up, anti-SARS-CoV-2 protein N total antibodies remained positive at the end of a follow-up period of 12.4 weeks median time (1–46, SD = 9.65) after the first positive determination. The blood group was not related to antibody waning. Lower lymphocyte counts and higher neutrophils would help predict future waning or decay of antibodies. Most recovered donors maintain their total anti-SARS-CoV-2 N protein antibodies for at least 16 weeks (at least one month must have been awaited from infection resolution to blood donation). The 10 individuals that could be followed up longer than 40 weeks (approximately 44 weeks after symptom’s relapse) were all still positive.

Anti-SARS-CoV-2 antibody decay after vaccination and immunogenicity of the booster dose of the BNT162b2 mRNA vaccine in patients with psoriatic arthritis on TNF inhibitors.

Scanty data on the anti- SARS-CoV-2 IgG level decay after two-dose BNT162b2 vaccination have been published in patients with psoriatic arthritis (PsA) on TNF inhibitors (TNFi). Similarly, no reports on the immunogenicity of a booster dose in such patients have been provided yet.We aimed to investigate the IgG level decay after two-dose BNT162b2 vaccination and the immunogenicity and safety of the booster dose in PsA patients on TNFi. Forty patients with classified PsA on TNFi undergoing booster dose with the BNT162b2 mRNA SARS- CoV-2 vaccine (BioNTech/Pfizer) were enrolled. Fifteen days after the third shot, serum IgG levels against SARS-CoV-2 (Abbott®ARCHITECT i2000SR, positivity cut-off 50 AU/mL) were assayed in all patients. Clinimetrics and treatment data were gathered. TNFi treatment was not discontinued. Sera from healthcare professionals were considered as healthy controls for 1:1 propensity score-matching. Student's t-test and logistic regression were used for investigating differences in immunogenicity between groups and predictors of antibody response. Even though the decay of IgG levels showed similar magnitude between groups, PsA patients had a lower IgG level than matched controls at 4 months after two-dose vaccination (2009.22±4050.22 vs. 6206.59±4968.33 AU/mL, respectively p=0.0006). Booster dose restored IgG levels to a similar extent in both groups (15846.47±12876.48 vs. 20374.46±12797.08 AU/ml p=0.20, respectively). Clinical Disease Activity Index (CDAI) did not change before and after vaccination (6.68±4.38 vs. 4.95±4.20, p=0.19). A BNT162b2 booster dose should be recommended in PsA patients on TNFi as its administration restores anti-SARS-CoV-2 IgG levels similar to healthy individuals.