Longitudinal analysis of antibody responses to the Pfizer BNT162b2 vaccine in Patients Undergoing Maintenance Hemodialysis

Background and objectives: Patients undergoing hemodialysis are at higher risk of developing severe complications upon SARS-CoV-2 infection and were prioritized in the Portuguese vaccination campaign. Immunogenicity of COVID-19 vaccines in hemodialyzed patients was not addressed by the phase 3 clinical trials leading to their emergency approval. Design, setting, participants, and measurements: We performed a prospective, longitudinal, cohort analysis of 156 hemodialyzed patients and 143 age-matched controls scheduled for BTN162b2 vaccine. Excluded from analysis were five patients previously diagnosed with SARS-CoV-2, three sero-positive for anti-SARS-CoV-2 N, two dropouts and two deaths. ELISA was used to quantify anti-full-length Spike IgG, IgM and IgA levels in sera collected at day of the first vaccine dose (t0); 3 weeks later (day of the second dose, t1); and 3 weeks after the second inoculation (t2). Results: Seroconversion after the first vaccine dose (t1) was remarkably low in patients, with positivity for anti-spike IgG, IgM and IgA antibodies of 29.4%, 12% and 41%, respectively. The second vaccine dose raised seroconversion to 90.9% and 83.9% for IgG and IgA, respectively, while IgM positivity remained unchanged. At t1 the anti-Spike IgG level was significantly lower in patients with ages below 70 years when compared to age-matched controls, showing a profile similar to aged individuals (above 70 years). Immunosuppression was associated with lower antibody responses along the vaccine schedule (p=0.005 at t1; p=0.008 at t2). Noteworthy, previous unresponsiveness to hepatitis B vaccination (75/129, 58% of patients negative for anti-HBs antibodies) did not correlate with humoral unresponsiveness to BTN162b2. Other clinical and laboratory parameters had marginal correlations with response to vaccination. Conclusions: The large majority of hemodialyzed patients showed IgG seroconversion upon BNT162b2 mRNA vaccination but a sizable proportion of patients presented poor responses. These results support further investigation into the relationship between vaccination, serologic response and host protection.

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Longitudinal Analysis of Antibody Responses to the mRNA BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis: A 6-Month Follow-Up

Frontiers in Medicine ◽

10.3389/fmed.2021.796676 ◽

2021 ◽

Vol 8 ◽

Author(s):

André Weigert ◽

Marie-Louise Bergman ◽

Lígia A. Gonçalves ◽

Iolanda Godinho ◽

Nádia Duarte ◽

...

Keyword(s):

Vaccination Campaign ◽

Cohort Analysis ◽

Vaccine Dose ◽

Maintenance Hemodialysis ◽

Poor Responders ◽

Induction Phase ◽

Close Monitoring ◽

Sizeable Fraction ◽

To Receive

Background: Patients on hemodialysis (HD) are at higher risk for COVID-19, overall are poor responders to vaccines, and were prioritized in the Portuguese vaccination campaign.Objective: This work aimed at evaluating in HD patients the immunogenicity of BTN162b2 after the two doses induction phase, the persistence of specific antibodies along time, and factors predicting these outcomes.Methods: We performed a prospective, 6-month long longitudinal cohort analysis of 156 HD patients scheduled to receive BTN162b2. ELISA quantified anti-spike IgG, IgM, and IgA levels in sera were collected every 3 weeks during the induction phase (t0 before vaccine; t1, d21 post first dose; and t2 d21 post second dose), and every 3–4 months during the waning phase (t3, d140, and t4, d180 post first dose). The age-matched control cohort was similarly analyzed from t0 to t2.Results: Upon exclusion of participants identified as previously exposed to SARS-CoV-2, seroconversion at t1 was lower in patients than controls (29 and 50%, respectively, p = 0.0014), while the second vaccine dose served as a boost in both cohorts (91 and 95% positivity, respectively, at t2, p = 0.2463). Lower response in patients than controls at t1 was a singularity of the participants ≤ 70 years (p = 2.01 × 10−05), associated with immunosuppressive therapies (p = 0.013), but not with lack of responsiveness to hepatitis B. Anti-spike IgG, IgM, and IgA levels decreased at t3, with IgG levels further waning at t4 and resulting in >30% seronegativity. Anti-spike IgG levels at t1 and t4 were correlated (ρ = 0.65, p < 2.2 × 10−16).Conclusions: While most HD patients seroconvert upon 2 doses of BNT162b2 vaccination, anti-spike antibodies levels wane over the following 4 months, leading to early seroreversion in a sizeable fraction of the patients. These findings warrant close monitoring of COVID-19 infection in vaccinated HD patients, and advocate for further studies following reinforced vaccination schedules.

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Antibody response to SARS-CoV-2 vaccination is extremely vivacious in subjects with previous SARS-CoV-2 infection

10.1101/2021.03.09.21253203 ◽

2021 ◽

Author(s):

Annapaola Callegaro ◽

Daniela Borleri ◽

Claudio Farina ◽

Gavino Napolitano ◽

Daniela Valenti ◽

...

Keyword(s):

Pearson Correlation ◽

Vaccination Campaign ◽

Vaccine Dose ◽

Vaccination Schedule ◽

Asymptomatic Infection ◽

Vaccine Injection ◽

Vaccine Schedule ◽

Pearson Correlation Test ◽

Speed Up ◽

Vaccination Campaigns

AbstractBackgroundThe SARS-CoV-2 pandemic calls for rapid actions, now principally oriented to a world-wide vaccination campaign.In this study we verified if, in individuals with a previous SARS-CoV-2 infection, a single dose of mRNA vaccine would be immunologically equivalent to a full vaccine schedule in naïve individuals.MethodsHealth care workers (184) with a previous SARS-CoV-2 infection were sampled soon before the second dose of vaccine and between 7 and 10 days after the second dose, the last sampling time was applied to SARS-CoV-2 naïve individuals, too.Antibodies against SARS-CoV-2 were measured using Elecsys® Anti-SARS-CoV-2 S immunoassay.The study was powered for non-inferiority. We used non parametric tests and Pearson correlation test to perform inferential analysis.ResultsAfter a single vaccine injection, the median titer of specific antibodies in individuals with previous COVID-19 was 30,527 U/ml (IQR 19,992-39,288) and in subjects with previous SARS-CoV-2 asymptomatic infection was 19,367.5 U/ml (IQR 14,688-31,353) (P=0.032). Both results were far above the median titer in naïve individuals after a full vaccination schedule: 1,974.5 U/ml (IQR 895-3,455) (P<0.0001). Adverse events after vaccine injection were more frequent after the second dose of vaccine (mean 0.95, 95%CI from 0.75 to 1.14 versus mean 1.91, 95%CI from 1.63 to 2.19)(P<0.0001) and in exposed compared to naïve (mean 1.63; 95%CI from 1.28 to 1.98 versus mean 2.35; 95%CI from 1.87 to 2.82)(P=0.015).ConclusionIn SARS-CoV-2 naturally infected individuals a single mRNA vaccine dose seems sufficient to reach immunity. Modifying current dosing schedules would speed-up vaccination campaigns.

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Resources, Production Scales and Time Required for Producing RNA Vaccines for the Global Pandemic Demand

Vaccines ◽

10.3390/vaccines9010003 ◽

2020 ◽

Vol 9 (1) ◽

pp. 3

Author(s):

Zoltán Kis ◽

Cleo Kontoravdi ◽

Robin Shattock ◽

Nilay Shah

Keyword(s):

Production Process ◽

Messenger Rna ◽

Vaccination Campaign ◽

Vaccine Dose ◽

Economic Feasibility ◽

Small Scale ◽

Production Scale ◽

Working Volume ◽

Global Demand ◽

The Impact

To overcome pandemics, such as COVID-19, vaccines are urgently needed at very high volumes. Here we assess the techno-economic feasibility of producing RNA vaccines for the demand associated with a global vaccination campaign. Production process performance is assessed for three messenger RNA (mRNA) and one self-amplifying RNA (saRNA) vaccines, all currently under clinical development, as well as for a hypothetical next-generation saRNA vaccine. The impact of key process design and operation uncertainties on the performance of the production process was assessed. The RNA vaccine drug substance (DS) production rates, volumes and costs are mostly impacted by the RNA amount per vaccine dose and to a lesser extent by the scale and titre in the production process. The resources, production scale and speed required to meet global demand vary substantially in function of the RNA amount per dose. For lower dose saRNA vaccines, global demand can be met using a production process at a scale of below 10 L bioreactor working volume. Consequently, these small-scale processes require a low amount of resources to set up and operate. RNA DS production can be faster than fill-to-finish into multidose vials; hence the latter may constitute a bottleneck.

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Self-reported and physiological reactions to the third BNT162b2 mRNA COVID-19 (booster) vaccine dose

10.1101/2021.09.15.21263633 ◽

2021 ◽

Author(s):

Merav Mofaz ◽

Matan Yechezkel ◽

Grace Guan ◽

Margaret L. Brandeau ◽

Tal Patalon ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Booster Dose ◽

Vaccination Campaign ◽

Vaccine Dose ◽

P Value ◽

Booster Vaccine ◽

The Third ◽

Systemic Reactions ◽

Physiological Reactions

AbstractBackgroundThe rapid rise in hospitalizations associated with the Delta-driven COVID-19 resurgence, and the imminent risk of hospital overcrowding, led the Israeli government to initialize a national third (booster) COVID-19 vaccination campaign in early August 2021, offering the BNT162b2 mRNA vaccine to individuals who received their second dose over five months ago. However, the safety of the third (booster) dose has not been fully established yet.ObjectiveEvaluate the short-term, self-reported and physiological reactions to the third BNT162b2 mRNA COVID-19 (booster) vaccine dose.DesignA prospective observational study, in which participants are equipped with a smartwatch and fill in a daily questionnaire via a dedicated mobile application for a period of 21 days, starting seven days before the vaccination.SettingAn Israel-wide third (booster) vaccination campaign.ParticipantsA group of 1,609 (18+ years of age) recipients of at least one dose of the BNT162b2 vaccine between December 20, 2020, and September 15, 2021, out of a larger cohort of 2,912 prospective study participants. 1,344 of the participants were recipients of the third vaccine dose.MeasurementsDaily self-reported questionnaires regarding local and systemic reactions, mood level, stress level, sport duration, and sleep quality. Heart rate, heart rate variability and blood oxygen saturation level were continuously measured by Garmin Vivosmart 4 smartwatches.ResultsThe extent of systemic reactions reported following the third (booster) dose administration is similar to that reported following the second dose (p-value=0.305) and considerably greater than that reported following the first dose (p-value<0.001). Our analyses of self-reported well-being indicators as well as the objective heart rate and heart rate variability measures recorded by the smartwatches further support this finding. Focusing on the third dose, reactions were more apparent in younger participants (p-value<0.01), in women (p-value<0.001), and in participants with no underlying medical conditions (p-value<0.001). Nevertheless, reported reactions and changes in physiological measures returned to their baseline levels within three days from inoculation with the third dose.LimitationsParticipants may not adequately represent the vaccinated population in Israel and elsewhere.ConclusionOur work further supports the safety of a third COVID-19 BNT162b2 mRNA (booster) vaccine dose from both a subjective and an objective perspective, particularly in individuals 65+ years of age and those with underlying medical conditions.Primary funding sourceEuropean Research Council (ERC) project #949850

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Antibody response to BTN162b2 mRNA vaccination in naïve versus SARS-CoV-2 infected subjects with and without waning immunity

10.21203/rs.3.rs-440410/v1 ◽

2021 ◽

Author(s):

Donato Zipeto ◽

Luca Dalle Carbonare ◽

Maria Teresa Valenti ◽

Zeno Bisoffi ◽

Chiara Piubelli ◽

...

Keyword(s):

Antibody Response ◽

Vaccine Dose ◽

Antibody Responses ◽

Serum Neutralization ◽

Iga Response ◽

Waning Immunity ◽

Specific Igg

Abstract We profiled antibody responses in a cohort of recipients of the BTN162b2 mRNA vaccine who were either immunologically naïve (n=50) or had been previously infected with SARS-CoV-2 (n=51). Of the previously infected, 25 and 26 were infected during the first and second pandemic waves in Italy, respectively; the majority of those from the first wave had corresponding waning immunity with low to undetectable levels of anti-S antibodies and low anti-N antibodies. We observed in recipients who had been previously infected that spike-specific IgG and pseudovirus neutralization titers were rapidly recalled by a single vaccine dose to higher levels than those in naïve recipients after the second vaccine dose, irrespective of waning immunity. In all recipients, a single vaccine dose was sufficient to induce a potent IgA response that was not associated with serum neutralization titers.

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Quantitative serological evaluation as a valuable tool in the COVID-19 vaccination campaign

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2021-0364 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Davide Ferrari ◽

Alessandra Mangia ◽

Maria Sestina Spanò ◽

Lucia Zaffarano ◽

Marco Viganò ◽

...

Keyword(s):

Immune Response ◽

General Population ◽

Serological Test ◽

Vaccination Campaign ◽

Age Groups ◽

Vaccine Dose ◽

Serum Samples ◽

Serological Tests ◽

Antibody Persistence ◽

Definition Of

Abstract Objectives After exceptional research efforts, several vaccines were developed against SARS-CoV-2 which sustains the pandemic COVID-19. The Comirnaty vaccine showed high efficacy in clinical trials and was the first to be approved for its distribution to the general population. We evaluated the immune response induced by the first vaccine dose in different sex/age groups and subjects with or without naturally present anti-SARS-CoV-2 antibodies. Methods As part of an Italian multicenter project (Covidiagnostix), serum samples from 4,290 health-professionals were serologically tested the day of the first vaccination dose, and 21 days later, using two different instrumentations (Siemens-Healthineers and Roche). Results In total, 97% of samples showed the presence of specific antibodies 21 days after the vaccination dose; the percentage of non-responders increased with age in both genders. Remarkably, naturally seropositive individuals showed antibody persistence up to 11 months and an exceptionally higher vaccination response compared to subjects never infected by SARS-CoV-2. Conclusions This study highlighted the importance of the serological test i) to identify naturally SARS-CoV-2 seropositive individuals and ii) to evaluate the antibody level elicited by the first vaccination dose. Both tests, highlighted differences in the immune response, when subjects were stratified by sex and age, and between naturally seropositive and seronegative subjects. The data obtained show how serological tests could play a crucial role in the triage of the population subjected to the vaccination campaign for COVID-19. The definition of suitable instrumentation-specific thresholds is needed to correctly follow eventually acquired post-vaccination immunity in the general population.

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Long-term persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein-specific and neutralizing antibodies in recovered COVID-19 patients

10.21203/rs.3.rs-1073046/v1 ◽

2021 ◽

Author(s):

Jira Chansaenroj ◽

Ritthideach Yorsaeng ◽

Nasamon Wanlapakorn ◽

Chintana Chirathaworn ◽

Natthinee Sudhinaraset ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Symptom Onset ◽

Neutralizing Antibodies ◽

Serum Antibody ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Spike Protein ◽

Immunological Study ◽

Igg Antibody ◽

Vaccine Schedule

Abstract Understanding antibody responses after natural severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can guide the coronavirus disease 2019 (COVID-19) vaccine schedule. This study aimed to assess the dynamics of SARS-CoV-2 antibodies, including anti-spike protein 1 (S1) immunoglobulin (Ig)G, anti-receptor-binding domain (RBD) total Ig, anti-S1 IgA, and neutralizing antibody against wild-type SARS-CoV-2 in a cohort of patients who were previously infected with SARS-CoV-2. Between March and May 2020, 531 individuals with virologically confirmed cases of SARS-CoV-2 infection were enrolled in our immunological study. The neutralizing titers against SARS-CoV-2 were detected in 95.2%, 86.7%, 85.0%, and 85.4% of recovered COVID-19 patients at 3, 6, 9, and 12 months after symptom onset, respectively. The seropositivity rate of anti-S1 IgG, anti-RBD total Ig, anti-S1 IgA, and neutralizing titers remained at 68.6%, 89.6%, 77.1%, and 85.4%, respectively, at 12 months after symptom onset. The half-life of neutralizing titers was estimated at 100.7 days (95% confidence interval = 44.5 – 327.4 days, R2 = 0.106). These results support that the decline in serum antibody levels over time depends on the symptom severity, and the individuals with high IgG antibody titers experienced a significantly longer persistence of SARS-CoV-2-specific antibody responses than those with lower titers.

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Can we predict antibody responses in SARS-CoV-2? A cohort analysis

10.1101/2021.03.15.21253267 ◽

2021 ◽

Author(s):

Mary Gaeddert ◽

Philip Kitchen ◽

Tobias Broger ◽

Stefan Weber ◽

Ralf Bartenschlager ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Severe Disease ◽

Cohort Analysis ◽

Antibody Responses ◽

High Antibody ◽

Igg Antibodies ◽

Rt Pcr ◽

Median Increase ◽

Antibody Titers

AbstractBackgroundAfter infection with severe acute respiratory syndrome coronavirus (SARS-CoV-2), Immunoglobulin G (IgG) antibodies and virus-specific neutralizing antibodies (nAbs) develop. This study describes antibody responses in a cohort of recovered COVID-19 patients to identify predictors.MethodsWe recruited patients with confirmed SARS-CoV-2 infection from Heidelberg, Germany. Blood samples were collected three weeks after COVID-19 symptoms ended. Participants with high antibody titers were invited for follow-up visits. IgG titers were measured by the Euroimmun Assay, and nAbs titers in a SARS-CoV-2 infection-based assay.Results281 participants were enrolled between April and August 2020 with IgG testing, 145 (51.6%) had nAbs, and 35 (12.5%) had follow-up. The median IgG optical density (OD) ratio was 3.1 (Interquartile range (IQR) 1.6-5.1), and 24.1% (35/145) had a nAb titer>1:80. Higher IgG titers were associated with increased age and more severe disease, and higher nAbs were associated with male gender and CT-value of 25-30 on RT-PCR at diagnosis. The median IgG OD ratio on follow-up was 3.7 (IQR 2.9-5.9), a median increase of 0.5 (IQR −0.3-1.7). Six participants with follow-up nAbs all had titers ≤ 1:80.ConclusionsWhile age and disease severity were correlated with IgG responses, predictive factors for nAbs in convalescent patients remain unclear.

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