The Slower Antibody Response in Myelofibrosis Patients after Two Doses of mRNA SARS-CoV-2 Vaccine Calls for a Third Dose

Immunization with mRNA SARS-CoV-2 vaccines has been highly recommended and prioritized in fragile subjects, including patients with myelofibrosis (MF). Available data on the vaccine immune response developed by MF patients and the impact of ruxolitinib treatment are still too fragmented to support an informed decision on a third dose for this category of subjects. Here, we show that 76% of MF patients develop spike-specific IgG after the second mRNA SARS-CoV-2 vaccine dose, but the response has a slower kinetics compared to healthy subjects, suggesting a reduced capability of their immune system to promptly react to vaccination. A reduced ACE2/RBD binding inhibition activity of spike-specific antibodies was also observed, especially in ruxolitinib-treated patients. Our results, showing slow kinetics of antibody responses in MF patients following vaccination with mRNA SARS-CoV-2 vaccines, support the need for a third vaccine dose.

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The slower antibody response in myelofibrosis patients after two doses of mRNA SARS-CoV-2 vaccine calls for a third dose

10.1101/2021.09.21.21263627 ◽

2021 ◽

Author(s):

Fabio Fiorino ◽

Anna Sicuranza ◽

Annalisa Ciabattini ◽

Adele Santoni ◽

Gabiria Pastore ◽

...

Keyword(s):

Healthy Subjects ◽

Vaccine Dose ◽

Binding Activity ◽

Antibody Responses ◽

Specific Antibodies ◽

Risk Of Mortality ◽

Specific Igg ◽

Open Question ◽

The Impact ◽

Slow Kinetic

Immunization with mRNA SARS-CoV-2 vaccines has been highly recommended and prioritized in fragile categories with higher risk of mortality after COVID-19 disease compared to healthy people, including patients with myelofibrosis (MF). Available data on the vaccine immune re-sponse developed by MF patients, and the impact of the treatment with the inhibitor of JAK-STAT signaling ruxolitimib, are still fragmented to support an informed decision for a third dose for this category of subjects. Here, we show that 76% of MF patients develop spike-specific IgG after the second vaccine dose, but the response has a slower kinetic compared to healthy subjects, suggesting a reduced capability of their immune system to promptly react to vaccina-tion. A reduced ACE2/RBD inhibition binding activity of spike-specific antibodies was also ob-served, especially in ruxolitimib treated patients. Our results contribute to answer the open question on the induction of the antibody responses in MF patients following vaccination with COVID-19 mRNA vaccines, showing a slow kinetic that support the need for a third dose of SARS-CoV-2 mRNA vaccines.

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Prospective Cohort Study of the Kinetics of Specific Antibodies to SARS-CoV-2 Infection and to Four SARS-CoV-2 Vaccines Available in Serbia, and Vaccine Effectiveness: A 3-Month Interim Report

Vaccines ◽

10.3390/vaccines9091031 ◽

2021 ◽

Vol 9 (9) ◽

pp. 1031

Author(s):

Olivera Lijeskić ◽

Ivana Klun ◽

Marija Stamenov Djaković ◽

Nenad Gligorić ◽

Tijana Štajner ◽

...

Keyword(s):

Real Life ◽

Vaccine Dose ◽

Igg Antibodies ◽

Post Vaccination ◽

Specific Antibodies ◽

Real Life Data ◽

Specific Igg ◽

Antibody Levels ◽

Kinetics Of ◽

Specific Igg Antibodies

Real-life data on the performance of vaccines against SARS-CoV-2 are still limited. We here present the rates of detection and levels of antibodies specific for the SARS-CoV-2 spike protein RBD (receptor binding domain) elicited by four vaccines available in Serbia, including BNT-162b2 (BioNTech/Pfizer), BBIBP-CorV (Sinopharm), Gam-COVID-Vac (Gamaleya Research Institute) and ChAdOx1-S (AstraZeneca), compared with those after documented COVID-19, at 6 weeks and 3 months post first vaccine dose or post-infection. Six weeks post first vaccine dose, specific IgG antibodies were detected in 100% of individuals fully vaccinated with BNT-162b2 (n = 100) and Gam-COVID-Vac (n = 12) and in 81.7% of BBIBP-CorV recipients (n = 148), while one dose of ChAdOx1-S (n = 24) induced specific antibodies in 75%. Antibody levels elicited by BNT-162b2 were higher, while those elicited by BBIBP-CorV were lower, than after SARS-CoV-2 infection. By 3 months post-vaccination, antibody levels decreased but remained ≥20-fold above the cut-off in BNT-162b2 but not in BBIBP-CorV recipients, when an additional 30% were seronegative. For all vaccines, antibody levels were higher in individuals with past COVID-19 than in naïve individuals. A total of twelve new infections occurred within the first 3 months post-vaccination, eight after the first dose of BNT-162b2 and ChAdOx1-S (one each) and BBIBP-CorV (six), and four after full vaccination with BBIBP-CorV, but none required hospitalization.

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Antibody responses to the BNT162b2 mRNA vaccine in individuals previously infected with SARS-CoV-2

Nature Medicine ◽

10.1038/s41591-021-01325-6 ◽

2021 ◽

Author(s):

Joseph E. Ebinger ◽

Justyna Fert-Bober ◽

Ignat Printsev ◽

Min Wu ◽

Nancy Sun ◽

...

Keyword(s):

Vaccine Dose ◽

Antibody Binding ◽

Antibody Responses ◽

Igg Antibody ◽

Binding Inhibition ◽

Specific Igg ◽

Antibody Levels ◽

Prior Infection

AbstractIn a cohort of BNT162b2 (Pfizer–BioNTech) mRNA vaccine recipients (n = 1,090), we observed that spike-specific IgG antibody levels and ACE2 antibody binding inhibition responses elicited by a single vaccine dose in individuals with prior SARS-CoV-2 infection (n = 35) were similar to those seen after two doses of vaccine in individuals without prior infection (n = 228). Post-vaccine symptoms were more prominent for those with prior infection after the first dose, but symptomology was similar between groups after the second dose.

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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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SARS-CoV-2-specific antibody detection for sero-epidemiology: a multiplex analysis approach accounting for accurate seroprevalence

10.1101/2020.06.18.20133660 ◽

2020 ◽

Cited By ~ 1

Author(s):

Gerco den Hartog ◽

Rutger M. Schepp ◽

Marjan Kuijer ◽

Corine GeurtsvanKessel ◽

Josine van Beek ◽

...

Keyword(s):

Multiplex Assay ◽

Spike Protein ◽

Antibody Detection ◽

Test Results ◽

Detailed Understanding ◽

Protein Subunits ◽

Specific Antibodies ◽

Single Antigen ◽

Specific Igg ◽

Kinetics Of

ABSTRACTBackgroundThe COVID-19 pandemic demands detailed understanding of the kinetics of antibody production induced by infection with SARS-CoV-2. We aimed to develop a high throughput multiplex assay to detect antibodies to SARS-CoV-2 to assess immunity to the virus in the general population.MethodsSpike protein subunits S1 and RBD, and Nucleoprotein were coupled to distinct microspheres. Sera collected before the emergence of SARS-CoV-2 (N=224), and of non-SARS-CoV-2 influenza-like illness (N=184), and laboratory-confirmed cases of SARS-CoV-2 infection (N=115) with various severity of COVID-19 were tested for SARS-CoV-2-specific concentrations of IgG.ResultsOur assay discriminated SARS-CoV-2-induced antibodies and those induced by other viruses. The assay obtained a specificity between 95.1 and 99.0% with a sensitivity ranging from 83.6-95.7%. By merging the test results for all 3 antigens a specificity of 100% was achieved with a sensitivity of at least 90%. Hospitalized COVID-19 patients developed higher IgG concentrations and the rate of IgG production increased faster compared to non-hospitalized cases.ConclusionsThe bead-based serological assay for quantitation of SARS-CoV-2-specific antibodies proved to be robust and can be conducted in many laboratories. Finally, we demonstrated that testing of antibodies against different antigens increases sensitivity and specificity compared to single antigen-specific IgG determination.

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Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients

Viruses ◽

10.3390/v12121390 ◽

2020 ◽

Vol 12 (12) ◽

pp. 1390

Author(s):

Anwar M. Hashem ◽

Abdullah Algaissi ◽

Sarah A. Almahboub ◽

Mohamed A. Alfaleh ◽

Turki S. Abujamel ◽

...

Keyword(s):

Disease Severity ◽

Neutralizing Antibodies ◽

Humoral Response ◽

Mortality Rates ◽

Antibody Responses ◽

High Morbidity ◽

Clinical Presentations ◽

Specific Igg ◽

Almost All ◽

Kinetics Of

The Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2, continues to spread globally with significantly high morbidity and mortality rates. Antigen-specific responses are of unquestionable value for clinical management of COVID-19 patients. Here, we investigated the kinetics of IgM, IgG against the spike (S) and nucleoproteins (N) proteins and their neutralizing capabilities in hospitalized COVID-19 patients with different disease presentations (i.e., mild, moderate or severe), need for intensive care units (ICU) admission or outcomes (i.e., survival vs death). We show that SARS-CoV-2 specific IgG, IgM and neutralizing antibodies (nAbs) were readily detectable in almost all COVID-19 patients with various clinical presentations. Interestingly, significantly higher levels of nAbs as well as anti-S1 and -N IgG and IgM antibodies were found in patients with more severe symptoms, patients requiring admission to ICU or those with fatal outcomes. More importantly, early after symptoms onset, we found that the levels of anti-N antibodies correlated strongly with disease severity. Collectively, these findings provide new insights into the kinetics of antibody responses in COVID-19 patients with different disease severity.

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Rapid response flow cytometric assay for the detection of antibody responses to SARS-CoV-2

10.1101/2020.05.09.20091447 ◽

2020 ◽

Cited By ~ 1

Author(s):

Dennis Lapuente ◽

Clara Maier ◽

Pascal Irrgang ◽

Julian Huebner ◽

Sophia Antonia Peter ◽

...

Keyword(s):

Antibody Responses ◽

Quantitative Detection ◽

Converting Enzyme ◽

Flow Cytometric Assay ◽

Angiotensin Converting Enzyme 2 ◽

Specific Antibodies ◽

Diagnostic Assays ◽

Flow Cytometric ◽

External Standard ◽

Specific Igg

SARS-CoV-2 has emerged as a previously unknown zoonotic coronavirus that spread worldwide causing a serious pandemic. While reliable nucleic acid-based diagnostic assays were rapidly available, there exists only a limited number of validated serological assays. Here, we evaluated a novel flow cytometric approach based on antigen-expressing HEK 293T cells to assess spike-specific IgG and IgM antibody responses. Analyses of 201 pre-COVID-19 sera proved a high assay specificity in comparison to commercially available CLIA and ELISA systems, while also revealing the highest sensitivity in specimens from PCR-confirmed SARS-CoV-2 infected patients. Additionally, a soluble Angiotensin-Converting-Enzyme 2 (ACE-2) variant was established as external standard to quantify spike-specific antibody responses on different assay platforms. In conclusion, our newly established flow cytometric assay allows sensitive and quantitative detection of SARS-CoV-2-specific antibodies, which can be easily adopted in different laboratories and does not rely on external supply of assay kits.

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Diminished antibody response against SARS-CoV-2 Omicron variant after third dose of mRNA vaccine in kidney transplant recipients

10.1101/2022.01.03.22268649 ◽

2022 ◽

Author(s):

Ayman Al Jurdi ◽

Rodrigo Benedetti Gassen ◽

Thiago De Jesus Borges ◽

Isadora Tadeval Lape ◽

Leela Morena ◽

...

Keyword(s):

Kidney Transplant ◽

Vaccine Dose ◽

Antibody Responses ◽

Transplant Recipients ◽

Wild Type ◽

Kidney Transplant Recipients ◽

Specific Antibodies ◽

Antiviral Responses ◽

The Third ◽

Donor Specific Antibodies

Abstract: Background: Available SARS-CoV-2 vaccines have reduced efficacy against the Omicron variant in immunocompetent individuals. Kidney transplant recipients (KTRs) have diminished antiviral responses to wild-type SARS-CoV-2 after vaccination, and data on antiviral responses to SARS-CoV-2 variants, including the Omicron variant, are limited. Methods: We conducted a prospective, multi-center cohort study of 51 adult KTRs who received three doses of BNT162b2 or mRNA-1273. Blood and urine samples were collected before and four weeks after the third vaccine dose. The primary outcome was anti-viral antibody responses against wild-type and variants of SARS-CoV-2. Secondary objectives included occurrence of breakthrough SARS-CoV-2 infection and non-invasive monitoring for rejection using serum creatinine, proteinuria, donor-derived cell-free DNA and donor-specific antibodies. Sera from pre-pandemic healthy controls and KTRs were used for comparison. Results: 67% of KTRs developed anti-wild-type spike antibodies after the third vaccine dose, similar to the Alpha (51%) and Beta (53%) variants, but higher than the Gamma (39%) and Delta (25%) variants. No KTRs had neutralizing responses to the Omicron variant before the third vaccine dose. After the third dose, fewer KTRs had neutralizing responses to the Omicron variant (12%) compared to wild-type (61%) and Delta (59%) variants. Three patients (6%) developed breakthrough SARS-CoV-2 infection at a median of 89 days. No KTRs developed allograft injury, de novo donor-specific antibodies or allograft rejection. Conclusion: In KTRs, a third dose of mRNA vaccines increases antibody responses against wild-type and variants of SARS-CoV-2, while neutralizing responses to the Omicron variant remain markedly reduced.

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Human IgG and IgA responses to COVID-19 mRNA vaccines

10.1101/2021.03.23.21254060 ◽

2021 ◽

Author(s):

Julian Campillo Luna ◽

Adam V Wisnewski ◽

Carrie A Redlich

Keyword(s):

Vaccine Dose ◽

Serum Levels ◽

Rapid Decline ◽

Natural Immunity ◽

Limited Information ◽

Viral Neutralization ◽

Time To Peak ◽

Specific Igg ◽

Kinetics Of

SARS-CoV-2 spike antigen-specific IgG and IgA elicited by infection mediate viral neutralization and are likely an important component of natural immunity, however, limited information exists on vaccine induced responses. We measured COVID-19 mRNA vaccine induced IgG and IgA in serum serially, up to 80 days post vaccination in 4 subjects. Spike antigen-specific IgG levels rose exponentially and plateaued 21 days after the initial vaccine dose. After the second vaccine dose IgG levels increased further, reaching a maximum approximately 7-10 days later, and remained elevated (average of 78% peak levels) during the additional 20-50 day follow up period. COVID-19 mRNA vaccination elicited spike antigen-specific IgA with similar kinetics of induction and time to peak levels, but more rapid decline in serum levels following both the 1st and 2nd vaccine doses (<23% peak levels within 80 days of the initial shot). The data demonstrate COVID-19 mRNA vaccines effectively induce spike antigen specific IgG and IgA and highlight marked differences in their persistence in serum.

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SARS-CoV-2–Specific Antibody Detection for Seroepidemiology: A Multiplex Analysis Approach Accounting for Accurate Seroprevalence

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa479 ◽

2020 ◽

Vol 222 (9) ◽

pp. 1452-1461 ◽

Cited By ~ 11

Author(s):

Gerco den Hartog ◽

Rutger M Schepp ◽

Marjan Kuijer ◽

Corine GeurtsvanKessel ◽

Josine van Beek ◽

...

Keyword(s):

Multiplex Assay ◽

Spike Protein ◽

Antibody Detection ◽

Receptor Binding Domain ◽

Test Results ◽

Protein Subunits ◽

Specific Antibodies ◽

Single Antigen ◽

Specific Igg ◽

Kinetics Of

Abstract Background The COVID-19 pandemic necessitates better understanding of the kinetics of antibody production induced by infection with SARS-CoV-2. We aimed to develop a high-throughput multiplex assay to detect antibodies to SARS-CoV-2 to assess immunity to the virus in the general population. Methods Spike protein subunits S1 and receptor binding domain, and nucleoprotein were coupled to microspheres. Sera collected before emergence of SARS-CoV-2 (n = 224) and of non-SARS-CoV-2 influenza-like illness (n = 184), and laboratory-confirmed cases of SARS-CoV-2 infection (n = 115) with various severities of COVID-19 were tested for SARS-CoV-2–specific IgG concentrations. Results Our assay discriminated SARS-CoV-2–induced antibodies and those induced by other viruses. The assay specificity was 95.1%–99.0% with sensitivity 83.6%–95.7%. By merging the test results for all 3 antigens a specificity of 100% was achieved with a sensitivity of at least 90%. Hospitalized COVID-19 patients developed higher IgG concentrations and the rate of IgG production increased faster compared to nonhospitalized cases. Conclusions The bead-based serological assay for quantitation of SARS-CoV-2–specific antibodies proved to be robust and can be conducted in many laboratories. We demonstrated that testing of antibodies against multiple antigens increases sensitivity and specificity compared to single-antigen–specific IgG determination.

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