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

Biomedicines ◽

10.3390/biomedicines9101480 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1480

Author(s):

Fabio Fiorino ◽

Anna Sicuranza ◽

Annalisa Ciabattini ◽

Adele Santoni ◽

Gabiria Pastore ◽

...

Keyword(s):

Healthy Subjects ◽

Vaccine Dose ◽

Antibody Responses ◽

Inhibition Activity ◽

Specific Antibodies ◽

Slow Kinetics ◽

Binding Inhibition ◽

Specific Igg ◽

The Impact ◽

Kinetics Of

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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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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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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Persistence of SARS-CoV-2-Specific Antibodies for 13 Months after Infection

Viruses ◽

10.3390/v13112313 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2313

Author(s):

Indrė Kučinskaitė-Kodzė ◽

Martynas Simanavičius ◽

Aistis Šimaitis ◽

Aurelija Žvirblienė

Keyword(s):

Serological Test ◽

Antibody Responses ◽

Serological Testing ◽

Rt Pcr ◽

Private Company ◽

Seropositivity Rate ◽

S Protein ◽

Specific Antibodies ◽

Specific Igg ◽

Second Wave

Background: Dynamics of antibody responses were investigated after a SARS-CoV-2 outbreak in a private company during the first wave of the pandemic. Methods: Workers of a sewing company (Lithuania) with known SARS-CoV-2 RT-PCR result during the outbreak (April 2020) were invited to participate in the study. Virus-specific IgG and IgM were monitored 2, 6 and 13 months after the outbreak via rapid IgG/IgM serological test and SARS-CoV-2 S protein-specific IgG ELISA. Results: Six months after the outbreak, 95% (CI 86–99%) of 59 previously infected individuals had virus-specific antibodies irrespective of the severity of infection. One-third of seropositive individuals had virus-specific IgM along with IgG indicating that IgM may persist for 6 months. Serological testing 13 months after the outbreak included 47 recovered individuals that remained non-vaccinated despite a wide accessibility of COVID-19 vaccines. The seropositivity rate was 83% (CI 69–91%) excluding one case of confirmed asymptomatic reinfection in this group. Between months 6 and 13, IgG levels either declined or remained stable in 31 individual and increased in 7 individuals possibly indicating an exposure to SARS-CoV-2 during the second wave of the pandemic. Conclusions: Detectable levels of SARS-CoV-2-specific antibodies persist up to 13 months after infection for the majority of the cases.

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A Single Dose of COVID-19 mRNA Vaccine Induces Airway Immunity in COVID-19 Convalescent Patients

10.1101/2021.12.16.21267932 ◽

2021 ◽

Author(s):

Charles Hugo MARQUETTE ◽

Emanuela MARTINUZZI ◽

Jonathan BENZAQUEN ◽

Olivier GUERIN ◽

Sylvie LEROY ◽

...

Keyword(s):

Single Dose ◽

Immune Responses ◽

Vaccine Dose ◽

Antibody Responses ◽

Igg Antibody ◽

Virus Shedding ◽

Booster Injection ◽

Specific Igg ◽

Mucosal Immune Responses ◽

Rna Vaccine

Background: Mucosal antibodies can prevent virus entry and replication in mucosal epithelial cells and hence virus shedding. Preclinical and clinical studies have shown that a parenteral booster injection of a vaccine against a mucosal pathogen promotes stronger mucosal immune responses following prior infection compared to two injections of a parenteral vaccine. We investigated whether this was also the case for a COVID-19 mRNA vaccine. Methods: Twenty-three COVID-19 convalescent patients and 20 SARS-CoV-2-naive subjects were vaccinated with respectively one and two doses of the Pfizer-BioNTech COVID-19 RNA vaccine. Nasal Epithelial Lining Fluid (NELF) and plasma were collected before and after vaccination and assessed for Immunoglobulin (Ig)G and IgA to Spike and for their ability to inhibit the binding of Spike to its ACE-2 receptor. Blood was analyzed one week after vaccination for the number of Spike-specific Antibody Secreting Cells (ASCs) with a mucosal tropism. Results: In COVID-19 convalescent patients, a single dose of vaccine amplified pre-existing Spike-specific IgG and IgA antibody responses in both NELF and blood against both vaccine homologous and variant strains, including delta. These responses were associated with Spike-specific IgG and IgA ASCs with a mucosal tropism in blood. Nasal IgA and IgG antibody responses were lower in magnitude in SARS-CoV-2-naive subjects after two vaccine doses Conclusion: This study showed that a parenteral booster injection of a COVID-19 RNA vaccine promoted stronger mucosal immune responses in COVID-19 convalescent patients compared to SARS-CoV-2 naive subjects who had received a first vaccine dose.

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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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Tear antibodies to SARS-CoV-2: implications for transmission

10.1101/2021.08.02.21261479 ◽

2021 ◽

Author(s):

Kevin John Selva ◽

Samantha K Davis ◽

Ebene R Haycroft ◽

Wen Shi Lee ◽

Ester Lopez ◽

...

Keyword(s):

Ocular Surface ◽

Post Infection ◽

Antibody Responses ◽

Healthy Controls ◽

Igg Antibodies ◽

Neutralising Antibodies ◽

Specific Antibodies ◽

Route Of Transmission ◽

Specific Igg ◽

Specific Igg Antibodies

Objectives SARS-CoV-2 can be transmitted by aerosols and the ocular surface may be an important route of transmission. Little is known about protective antibody responses to SARS-CoV-2 in tears after infection or vaccination. We analysed SARS-CoV-2 specific IgG and IgA responses in human tears after either COVID-19 infection or vaccination. Methods We recruited 16 subjects with COVID-19 infection an average of 7 months previously and 15 subjects before and 2 weeks after Comirnaty (Pfizer-BioNtech) vaccination. Plasma, saliva and basal tears were collected. Pre-pandemic plasma, saliva and basal tears from 11 individuals were included as healthy controls. Antibody responses to 5 SARS-CoV-2 antigens were measured via multiplex. Results IgG antibodies to Spike and Nucleoprotein were detected in tears, saliva and plasma from subjects with prior SARS-CoV-2 infection in comparison to uninfected controls. While RBD-specific antibodies were detected in plasma, minimal RBD-specific antibodies were detected in tears and saliva. In contrast, high levels of IgG antibodies to Spike and RBD, but not Nucleoprotein, were induced in tears, saliva and plasma of subjects receiving 2 doses of the Comirnaty vaccine. Increased levels of IgA1 and IgA2 antibodies to SARS-CoV-2 antigens were detected in plasma following infection or vaccination, but were unchanged in tears and saliva. Conclusion Both infection and vaccination induce SARS-CoV-2-specific IgG antibodies in tears. RBD-specific IgG antibodies in tears were induced by vaccination but were not present 7 months post-infection. This suggests neutralising antibodies may be low in the tears late following infection.

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An intranasal vaccine durably protects against SARS-CoV-2 variants in mice

10.1101/2021.05.08.443267 ◽

2021 ◽

Author(s):

Ahmed O Hassan ◽

Swathi Shrihari ◽

Matthew J Gorman ◽

Baoling Ying ◽

Dansu Yuan ◽

...

Keyword(s):

Plasma Cells ◽

Dose Range ◽

Vaccine Dose ◽

Antibody Responses ◽

Spike Protein ◽

Protective Activity ◽

Complete Protection ◽

Intranasal Vaccine ◽

Specific Igg ◽

Vectored Vaccine

SARS-CoV-2 variants that attenuate antibody neutralization could jeopardize vaccine efficacy and the end of the COVID-19 pandemic. We recently reported the protective activity of a single-dose intranasally-administered spike protein-based chimpanzee adenovirus-vectored vaccine (ChAd-SARS-CoV-2-S) in animals, which has advanced to human trials. Here, we assessed its durability, dose-response, and cross-protective activity in mice. A single intranasal dose of ChAd-SARS-CoV-2-S induced durably high neutralizing and Fc effector antibody responses in serum and S-specific IgG and IgA secreting long-lived plasma cells in the bone marrow. Protection against a historical SARS-CoV-2 strain was observed across a 100-fold vaccine dose range and over a 200-day period. At 6 weeks or 9 months after vaccination, serum antibodies neutralized SARS-CoV-2 strains with B.1.351 and B.1.1.28 spike proteins and conferred almost complete protection in the upper and lower respiratory tracts after challenge. Thus, in mice, intranasal immunization with ChAd-SARS-CoV-2-S provides durable protection against historical and emerging SARS-CoV-2 strains.

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Surface Engineering of Recombinant RNA Coliphage Qβ to Display gp41 MembraneProximal External-Region Epitopes from HIV-1

Journal of Clinical & Experimental Immunology ◽

10.33140/jcei.002.01.04 ◽

2017 ◽

Vol 2 (1) ◽

Keyword(s):

Immune System ◽

Coat Protein ◽

Antibody Responses ◽

Igg Antibody ◽

External Region ◽

Specific Antibodies ◽

Infected People ◽

Specific Igg ◽

Minor Coat Protein ◽

Hiv 1

Introduction: The membrane proximal external region (MPER) of HIV-1 envelope glycoprotein-41 (gp41) is targeted by several broadly neutralizing antibodies whose conserved linear epitopes are promising targets for vaccine design. However, a formidable challenge has remained the difficulty to design and deliver MPER based immunogens for the efficient induction of such broadly neutralizing HIV-1 specific antibodies (bnAb). This is mainly because the linear bnAb MPER epitopes are poorly accessible to the immune system. The overall objective of this study therefore was the development of a novel RNA Qβ phage display system not only for monitoring anti-MPER specific antibody responses but equally as potential immunogens in future HIV-1 vaccine designs. Method: To overcome the challenge of effective presentation of MPER to the immune system we have selectively engineered the surface of the RNA coliphage Qβ to expose all MPER bnAb epitopes. Briefly, DNA representing a 50 amino acids consensus region within the HIV-1 gp41 MPER was fused in frame with the minor coat protein A1of the Qβ phage. Three variant MPER expression cassettes were obtained with the MPER cDNA in frame with the minor coat protein A1 gene, including pQβMPER, pQβMPERHis and pQβMPERN. The expression cassettes were used for the production of QβMPER recombinant phages after transformation of E. coli HB101 strain. Antigencity of the phages was assessed with plasma from long standing anti-retroviral naïve HIV-1 infected people from the CIRCB AFRODEC cohort while immunogenicity studies were done in female Balb/c mice. Results: The initial titers of all recombinant phages including QβMPER, QβMPERHis and QβMPERN were 104 plaque forming units/ml (pfu/ml). This was significantly lower (P<0.001) relative to the 108 pfu/ml of wild type phage, but was scaled up to 1014pfu/ml. The fusion of MPER and Qβ genes was confirmed by RT-PCR followed by gel electrophoresis and sequencing. Specific recognition of some reported bnAb epitopes within MPER were confirmed in ELISA using the three recombinant QβMPER phages together with an MPER restrictive peptide as antigens and the bnAb 4E10, Z13e1, 2F5 and 10E8 as antibodies. Next the prevalence of MPER-specific antibodies was determined in plasma from long standing antiretroviral naïve HIV-1 infected participants of the CIRCB AFRODEC cohort. The greater majority (84%) of participants’ plasma showed MPER peptide specific reactivity with anti-MPER specific IgG antibody titers ranging from 200 to 409600 comparative to background IgG antibody titer with the Qβ phage alone as antigen or plasma from seronegative participants. In immunogenicity studies in Balb/c mice the recombinant phages QβMPERN and QβMPERHis induced significantly high Anti-MPER-specific IgG antibody responses (P<0.04) in at least 60 % of mice following three inoculations of each recombinant phage. Conclusion: Thus, these novel recombinantQβMPER phages can be used to monitor MPER-specific immune responses in HIV-1 exposed or infected people. In addition the recombinant QβMPER phages could be used as immunogens either alone as demonstrated here in mice or in combination with other strategies for the induction of MPER specific immunity against HIV-1.

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