scholarly journals Successful Anti-SARS-CoV-2 Spike Protein Antibody Response to Vaccination in MAGT1 Deficiency

2021 ◽  
Vol 12 ◽  
pp. 215265672110562
Author(s):  
Maaz Jalil ◽  
Marija Rowane ◽  
Jayanth Rajan ◽  
Robert Hostoffer
Keyword(s):  
Antibody Response ◽  
Messenger Rna ◽  
Neutralizing Antibodies ◽  
Office Visit ◽  
Spike Protein ◽  
Antibody Detection ◽  
Epstein Barr Virus Infection ◽  
Protein Antigens ◽  
Antibody Testing ◽  
Post Vaccination

Background Novel messenger RNA vaccines against severe acute respiratory syndrome coronavirus (SARS-CoV-2) have been vital in resolving the coronavirus disease-2019 (COVID-19) pandemic. Detection of neutralizing antibodies (NAbs) against the SARS-CoV-2 spike protein (S) confirms immunogenicity with high sensitivity and specificity. Few recent studies with primary and secondary immunodeficient cohorts present adequate or reduced antibody response. We describe the first reported successful response to anti-SARS-CoV-2 S antibody post-vaccination in magnesium transporter 1 (MAGT1) gene deficiency, more commonly recognized as x-linked immunodeficiency with magnesium defect, Epstein-Barr Virus infection, and neoplasia (XMEN). Case Presentation We present a 30-year-old male with selective anti-polysaccharide antibody deficiency, peripheral blood CD5  +  /CD19  +  B-cell predominance (97%), MAGT1 mutation, and reduced CD16  +  CD56  +  natural killer- and/or CD8  +  T-cell receptor, Group 2, Member D expression. His initial immunological evaluation revealed all seronegative post-vaccination antibody titers but clinically adequate response to protein antigens tetanus and diphtheria anti-toxoids. COVID-19 vaccination and associated serology antibody testing was recommended at this office visit. Anti-SARS-CoV-2 immunoglobulin (Ig)M and IgG antibodies before and after the first BNT162b2 mRNA COVID-19 vaccine doses, as well as nucleocapsid antibody, were negative. S protein total antibody was reactive after the second dose. Discussion Robust immunological sequelae post-COVID-19 vaccination in the general population are well-documented in the recent literature. Few studies have evaluated COVID-19 vaccination antibody response in immunodeficient patients. The majority positive anti-S antibody detection in most primary immunodeficient (PID) patients among the few studies in the literature, such as the present case, support the safety and efficacy of mRNA COVID-19 vaccination in immunodeficient patients, although larger scale studies are needed. Conclusion We demonstrate successful vaccination in the PID MAGT1 deficiency in this first reported case of reactive anti-S antibody post-COVID-19 vaccination.

scholarly journals Antibody repertoire induced by SARS-CoV-2 spike protein immunogens

2020 ◽  
Author(s):  
Supriya Ravichandran ◽  
Elizabeth M. Coyle ◽  
Laura Klenow ◽  
Juanjie Tang ◽  
Gabrielle Grubbs ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Neutralization Assay ◽  
Spike Protein ◽  
Antibody Repertoire ◽  
Limited Information ◽  
Protein Antigens ◽  
Phage Display Libraries ◽  
Rational Vaccine Design ◽  
And Function

ABSTRACTMultiple vaccine candidates against SARS-CoV-2 based on viral spike protein are under development. However, there is limited information on the quality of antibody response generated following vaccination by these vaccine modalities. To better understand antibody response induced by spike protein-based vaccines, we immunized rabbits with various SARS-CoV-2 spike protein antigens: S-ectodomain (S1+S2) (aa 16-1213), which lacks the cytoplasmic and transmembrane domains (CT-TM), the S1 domain (aa 16-685), the receptor-binding domain (RBD) (aa 319-541), and the S2 domain (aa 686-1213 as control). Antibody response was analyzed by ELISA, Surface Plasmon Resonance (SPR) against different Spike proteins in native conformation, and a pseudovirion neutralization assay to measure the quality and function of the antibodies elicited by the different Spike antigens. All three antigens (S1+S2 ectodomain, S1 domain, and RBD) generated strong neutralizing antibodies against SARS-CoV-2. Vaccination induced antibody repertoire was analyzed by SARS-CoV-2 spike Genome Fragment Phage Display Libraries (SARS-CoV-2 GFPDL), which identified immunodominant epitopes in the S1, S1-RBD and S2 domains. Furthermore, these analyses demonstrated that surprisingly the RBD immunogen elicited a higher antibody titer with 5-fold higher affinity antibodies to native spike antigens compared with other spike antigens. These findings may help guide rational vaccine design and facilitate development and evaluation of effective therapeutics and vaccines against COVID-19 disease.One Sentence SummarySARS-CoV-2 Spike induced immune response

scholarly journals Evaluation of Antibody Response to Heterologous Prime–Boost Vaccination with ChAdOx1 nCoV-19 and BNT162b2: An Observational Study

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1478
Author(s):  
Davide Firinu ◽  
Andrea Perra ◽  
Marcello Campagna ◽  
Roberto Littera ◽  
Federico Meloni ◽  
...  
Keyword(s):  
Observational Study ◽  
Antibody Response ◽  
Messenger Rna ◽  
Healthy Subjects ◽  
Booster Dose ◽  
Spike Protein ◽  
National Guidelines ◽  
Vector Vaccine ◽  
Boost Vaccination ◽  
Serum Igg

In several countries, thrombotic events after vaccination with ChAdOx1 nCoV-19 have led to heterologous messenger RNA (mRNA) boosting. We tested the antibody response to SARS-CoV-2 spike protein four weeks after heterologous priming with the ChAdOx1 (ChAd) vector vaccine followed by boosting with BNT162b2(ChAd/BNT), comparing data of homologous regimen (BNT/BNT, ChAd/ChAd) subjects positive for SARS-CoV-2 after the first dose of BNT162b2 (BNT1dose/CoV2) and convalescent COVID-19. Methods: healthy subjects naïve for SARS-CoV-2 infection were assessed for serum IgG anti-S-RBD response 21 days after priming (T1), 4 (TFULL) and 15 (T15W) weeks after booster dose. Results: The median IgG anti-S-RBD levels at TFULL of Chad/BNT group were significantly higher than the BNT/BNT group and ChAd/ChAd. Those of BNT/BNT group were significantly higher than ChAd/ChAd. IgG anti-S-RBD of BNT1dose/CoV2 group were similar to BNT/BNT, ChAd/BNT and ChAd/Chad group. The levels among COVID-19 convalescents were significantly lower than ChAd/BNT, BNT/BNT, ChAd/Chad and BNT1dose/CoV2. The proportion of subjects reaching an anti-S-RBD titer >75 AU/mL, correlated with high neutralizing titer, was 94% in ChAd/BNT and BNT/BNT, 60% in BNT1dose/CoV2, 25% in ChAd/ChAd and 4.2% in convalescents. At T15W the titer of ChAd/BNT was still significantly higher than other vaccine schedules, while the anti-S-RBD decline was reduced for ChAd/ChAd and similar for other combinations. Conclusion: Our data highlight the magnitude of IgG anti-S-RBD response in ChAd/BNT dosing, supporting the current national guidelines for heterologous boosting

scholarly journals Robust SARS-CoV-2 Antibody Responses in Asian COVID-Naïve Subjects 180 Days after Two Doses of BNT162b2 mRNA COVID-19 Vaccine

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1241
Author(s):  
Chin-Shern Lau ◽  
Soon Kieng Phua ◽  
Ya-Li Liang ◽  
Helen May-Lin Oh ◽  
Tar-Choon Aw
Keyword(s):  
Regression Analysis ◽  
Linear Regression ◽  
Antibody Response ◽  
Southeast Asia ◽  
Neutralizing Antibodies ◽  
Linear Regression Analysis ◽  
Antibody Responses ◽  
Post Vaccination ◽  
Non Linear ◽  
Antibody Panel

Background: Subjects with previous COVID-19 have augmented post-vaccination responses. However, the antibody response in COVID-naïve subjects from Southeast Asia is not well known. Methods: 77 COVID-naïve vaccinees were tested with a full antibody panel [spike antibodies (total (T-Ab), IgG, IgM) and neutralizing antibodies (N-Ab)] pre-vaccination, 10 days after dose 1, and 20/40/60/90/120/150/180 days after dose 2. Results: 10 days after dose 1, 67.6% (48/71)/69.0% (49/71) were T-Ab/IgG positive; only 15.5% (11/71)/14.1% (10/71) were N-Ab/IgM positive. While all (100%) subjects had brisk T-Ab, IgG and N-Ab antibody responses 20 days after complete vaccination, only 79.1% (53/67) were IgM positive. At 180 days (n = 8), T-Ab/IgG/N-Ab were still reactive (lowest T-Ab 186 U/mL, IgG 617 AU/mL, N-Ab 0.39 µg/mL), but IgM was negative in all samples. Spike antibody thresholds of T-Ab 74.1 U/mL (r = 0.95) and IgG 916 AU/mL (r = 0.95) corresponded to N-Ab reactivity (>0.3 µg/mL). Non-linear regression analysis showed that N-Ab would decrease to 0.3 µg/mL by 241 days, whereas T-Ab/IgG would need 470/163 days to reach titers of T-Ab/IgG associated with a N-Ab 0.3 µg/mL (76.4 U/mL and 916 AU/mL respectively). Conclusions: The antibody responses of T-Ab, IgG and N-Ab remain high and durable even at 180 days. N-Ab titers are expected to remain reactive up to 241 days post-vaccination.

scholarly journals Effect Monitoring and Insights from Vaccination program of Healthcare Workforce from a tertiary level hospital in India against SARS-CoV-2

2021 ◽  
Author(s):  
Rajat Ujjainia ◽  
Akansha Tyagi ◽  
Viren Sardana ◽  
Salwa Naushin ◽  
Nitin Bhatheja ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Healthcare Workers ◽  
Protein S ◽  
Maximum Increase ◽  
Post Vaccination ◽  
Neutralizing Activity ◽  
Effect Monitoring ◽  
Antibody Levels ◽  
Level Hospital

AbstractThe Oxford-Astra Zeneca COVID 19 vaccine (AZD1222 or ChAdOx1) is locally manufactured as Covishield by Serum Institute, Pune, India. In a group of 307 healthcare workers administered Covishield, we report measured antibody response to SARS-CoV-2 directed against the spike protein (S-antigen) at days 0, 7, 14, 28 and 45, with second dose on day 28 for all except 20 subjects who did not receive a second dose. In 129 subjects (42%) who had already developed antibodies to SARS-CoV-2 at day 0 (before immunization), it was observed that antibody response was significantly higher at each time point, with the maximum increase seen between days 0 and 7. The antibody levels and neutralizing activity in these subjects had peaked by day 28 and the second dose did not lead to further increase. Data from 9 subjects who were seropositive at baseline and received only one dose was similar to those who received both doses. In contrast the baseline sero-negative group (n=178) started developing antibody response only after 14 days or later. Administration of the second dose was associated with further increase in antibody levels at day 45 compared to day 28, with marked increase in neutralizing activity. In baseline seronegative subjects, who did not take the vaccine at day 28 (n=11), the antibody levels increased by about 2.5 folds between days 28 and 45, with minimal change in the neutralizing antibodies. In general, vaccination was well tolerated, and there were no group specific differences in post-vaccination symptomatology. Our data suggests that ChAdOx1 is highly immunogenic, particularly so where previous SARS CoV2 antibody-response is established. In such subjects, a single dose may be sufficient but in absence of such determination, both doses are required.

scholarly journals A Mycobacteriophage-Based Vaccine Platform: SARS-CoV-2 Antigen Expression and Display

2021 ◽  
Vol 9 (12) ◽  
pp. 2414
Author(s):  
Krista G. Freeman ◽  
Katherine S. Wetzel ◽  
Yu Zhang ◽  
Kira M. Zack ◽  
Deborah Jacobs-Sera ◽  
...  
Keyword(s):  
Single Particle ◽  
High Purity ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Antigen Expression ◽  
Spike Protein ◽  
Infectious Agents ◽  
Protein Antigens ◽  
Vaccine Platform ◽  
Excellent Safety Profile

The explosion of SARS-CoV-2 infections in 2020 prompted a flurry of activity in vaccine development and exploration of various vaccine platforms, some well-established and some new. Phage-based vaccines were described previously, and we explored the possibility of using mycobacteriophages as a platform for displaying antigens of SARS-CoV-2 or other infectious agents. The potential advantages of using mycobacteriophages are that a large and diverse variety of them have been described and genomically characterized, engineering tools are available, and there is the capacity to display up to 700 antigen copies on a single particle approximately 100 nm in size. The phage body may itself be a good adjuvant, and the phages can be propagated easily, cheaply, and to high purity. Furthermore, the recent use of these phages therapeutically, including by intravenous administration, suggests an excellent safety profile, although efficacy can be restricted by neutralizing antibodies. We describe here the potent immunogenicity of mycobacteriophage Bxb1, and Bxb1 recombinants displaying SARS-CoV-2 Spike protein antigens.

scholarly journals Potent anti-SARS-CoV-2 Antibody Responses are Associated with Better Prognosis in Hospital Inpatient COVID-19 Disease

2020 ◽  
Author(s):  
Patrick J Tighe ◽  
Richard A Urbanowicz ◽  
Lucy Fairclough ◽  
C Patrick McClure ◽  
Brian J Thomson ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Clinical Intervention ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Spike Protein ◽  
Effective Vaccine ◽  
Hospital Inpatient ◽  
Protein Variant ◽  
Immune Correlates

COVID-19 continues to cause a pandemic, having infected more than 20 million people globally. Successful elimination of the SARS-CoV-2 virus will require an effective vaccine. However, the immune correlates of infection are currently poorly understood. While neutralizing antibodies are believed to be essential for protection against infection, the contribution of the neutralizing antibody response to resolution of SARS-CoV-2 infection has not yet been defined. In this study the antibody responses to the SARS-CoV-2 spike protein and nucleocapsid proteins were investigated in a UK patient cohort, using optimised immunoassays and a retrovirus-based pseudotype entry assay. It was discovered that in severe COVID-19 infections an early antibody response to both antigens was associated with improved prognosis of infection. While not all SARS-CoV-2-reactive sera were found to possess neutralizing antibodies, neutralizing potency of sera was found to be greater in patients who went on to resolve infection, compared with those that died from COVID-19. Furthermore, viral genetic variation in spike protein was found to influence the production of neutralizing antibodies. Infection with the recently described spike protein variant 614G produced higher levels of neutralizing antibodies when compared to viruses possessing the 614D variant. These findings support the assertion that vaccines targeting generation of neutralizing antibodies may be useful at limiting SARS-CoV-2 infection. Assessment of the antibody responses to SARS-CoV-2 at time of diagnosis will be a useful addition to the diagnostic toolkit, enabling stratification of clinical intervention for severe COVID-19 disease.

scholarly journals Antibody signature induced by SARS-CoV-2 spike protein immunogens in rabbits

2020 ◽  
Vol 12 (550) ◽  
pp. eabc3539 ◽  
Author(s):  
Supriya Ravichandran ◽  
Elizabeth M. Coyle ◽  
Laura Klenow ◽  
Juanjie Tang ◽  
Gabrielle Grubbs ◽  
...  
Keyword(s):  
Amino Acids ◽  
Neutralizing Antibodies ◽  
Antibody Responses ◽  
Spike Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Limited Information ◽  
Protein Antigens ◽  
Phage Display Libraries ◽  
Rational Vaccine Design ◽  
And Function

Multiple vaccine candidates against SARS-CoV-2 based on viral spike protein are under development. However, there is limited information on the quality of antibody responses generated with these vaccine modalities. To better understand antibody responses induced by spike protein–based vaccines, we performed a qualitative study by immunizing rabbits with various SARS-CoV-2 spike protein antigens: S ectodomain (S1+S2; amino acids 16 to 1213), which lacks the cytoplasmic and transmembrane domains (CT-TM), the S1 domain (amino acids 16 to 685), the receptor binding domain (RBD) (amino acids 319 to 541), and the S2 domain (amino acids 686 to 1213, lacking the RBD, as control). Resulting antibody quality and function were analyzed by enzyme-linked immunosorbent assay (ELISA), RBD competition assay, surface plasmon resonance (SPR) against different spike proteins in native conformation, and neutralization assays. All three antigens (S1+S2 ectodomain, S1 domain, and RBD), but not S2, generated strong neutralizing antibodies against SARS-CoV-2. Vaccination-induced antibody repertoire was analyzed by SARS-CoV-2 spike genome fragment phage display libraries (SARS-CoV-2 GFPDL), which identified immunodominant epitopes in the S1, S1-RBD, and S2 domains. Furthermore, these analyses demonstrated that the RBD immunogen elicited a higher antibody titer with five-fold higher affinity antibodies to native spike antigens compared with other spike antigens, and antibody affinity correlated strongly with neutralization titers. These findings may help guide rational vaccine design and facilitate development and evaluation of effective therapeutics and vaccines against COVID-19 disease.

scholarly journals A Peptide-Based Assay Discriminates Individual Antibody Response to the COVID-19 Pfizer/BioNTech mRNA Vaccine

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 987
Author(s):  
Immacolata Polvere ◽  
Serena Voccola ◽  
Alfredina Parrella ◽  
Gaetano Cardinale ◽  
Lucrezia Zerillo ◽  
...  
Keyword(s):  
Antibody Response ◽  
Synthetic Peptides ◽  
Neutralizing Antibodies ◽  
Spike Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Published Data ◽  
Time Points ◽  
Good Production ◽  
Neutralizing Capacity ◽  
Temporal Persistence

The coronavirus disease 2019 (COVID-19) mRNA vaccine developed by Pfizer/BioNTech has been shown to be capable of developing an excellent antibody response against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, with good production of neutralizing antibodies. Herein, we analyzed differences in the antibody response elicited by inoculation of the Pfizer/BioNTech vaccine through a peptide-based enzyme-linked immunosorbent assay (ELISA) that utilizes synthetic peptides derived from the spike protein in the immuno-adsorbent phase. Immunoreactivity against synthetic peptides was measured at different time points from vaccination and was also correlated with the SARS-CoV-2 neutralizing capacity. Our results indicate that all vaccinated subjects except one show reactive antibodies to at least one peptide at both 30 and 60 days after injection of the first dose. Only one of the 19 analyzed subjects showed no antibody response toward any of the selected peptides, consistently with a lower neutralizing capacity. More importantly, our data showed that the antibody response elicited by inoculation of the two doses of the Pfizer vaccine appears to be qualitatively individual, both in the type of recognized peptides and in the temporal persistence of the antibody response. Together with previous published data, our findings suggest that for effective pandemic control, it is important to constantly monitor the antibody protection in the population, and the assay described here could be a valid tool for this purpose.

scholarly journals Seasonal Betacoronavirus Antibodies’ Expansion Post-BNT161b2 Vaccination Associates with Reduced SARS-CoV-2 VoC Neutralization

2022 ◽  
Author(s):  
Stefania Dispinseri ◽  
Ilaria Marzinotto ◽  
Cristina Brigatti ◽  
Maria Franca Pirillo ◽  
Monica Tolazzi ◽  
...  
Keyword(s):  
Health Care ◽  
Health Care Workers ◽  
Neutralizing Antibodies ◽  
Spike Protein ◽  
Post Vaccination ◽  
Care Workers ◽  
Sequential Samples ◽  
Alpha Beta ◽  
Antibody Levels ◽  
Neutralization Ability

AbstractSARS-CoV-2 vaccination is known to induce antibodies that recognize also variants of concerns (VoCs) of the virus. However, epidemiological and laboratory evidences indicate that these antibodies have a reduced neutralization ability against VoCs. We studied binding and neutralizing antibodies against the Spike protein domains and subunits of the Wuhan-Hu-1 virus and its alpha, beta, delta VoCs and of seasonal betacoronaviruses (HKU1 and OC43) in a cohort of 31 health care workers prospectively followed post-vaccination with BNT162b2-Comirnaty. The study of sequential samples collected up to 64 days post-vaccination showed that serological assays measuring IgG against Wuhan-Hu-1 antigens were a poor proxy for VoC neutralization. In addition, in subjects who had asymptomatic or mild COVID-19 prior to vaccination, the loss of nAbs following disease could be rapid and accompanied by post-vaccination antibody levels similar to those of naïve vaccinees. Interestingly, in health care workers naïve for SARS-CoV-2 infection, vaccination induced a rapid and transient reactivation of pre-existing seasonal coronaviruses IgG responses that was associated with a subsequent reduced ability to neutralize alpha and beta VoCs.

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