Anti-SARS-CoV-2 S-RBD IgG Antibody Responses after COVID-19 mRNA Vaccine in the Chronic Disorder of Consciousness: A Pilot Study

Objective: In the last year, a large amount of research has investigated the anti-spike protein receptor-binding domain (S-RBD) antibody responses in patients at high risk of developing severe acute respiratory syndrome because of COVID-19 infection. However, no data are available on the chronic disorder of consciousness (DOC). Methods: Here, we evaluated anti-S-RBD IgG levels after vaccination in chronic DOC patients compared with demographically matched healthy controls (HC) by indirect chemiluminescence immunoassay. All individuals completed a two-dose-cycle vaccination with Pfizer mRNA vaccine (BNT162b2), and antibody responses were evaluated at 30 and 180 days after the administration of the second dose of vaccination. Results: We compared 32 DOC patients with 34 demographically matched healthy controls. Both DOC and HC groups showed a similar antibody response at 30 days, whereas at follow-up (180 days) DOC patients were characterized by lower S-RBD IgG levels with respect to controls. Additional multiple regression analyses including demographical and clinical comorbidities as predictors revealed that age was the only factor associated with the decrease in S-RBD IgG levels at follow-up (180 days). Elderly individuals of both groups were characterized by a reduction in the antibody responses with respect to younger individuals. Conclusions: Our results show an efficacy seroconversion in DOC patients in the first period after vaccination, which significantly declines over time with respect to healthy controls.

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Progression to type 2 diabetes in women with a known history of gestational diabetes: systematic review and meta-analysis

BMJ ◽

10.1136/bmj.m1361 ◽

2020 ◽

pp. m1361 ◽

Cited By ~ 16

Author(s):

Elpida Vounzoulaki ◽

Kamlesh Khunti ◽

Sophia C Abner ◽

Bee K Tan ◽

Melanie J Davies ◽

...

Keyword(s):

Diabetes Mellitus ◽

Systematic Review ◽

Meta Analysis ◽

Healthy Controls ◽

Regression Analyses ◽

White Population ◽

History Of ◽

Meta Regression

AbstractObjectiveTo estimate and compare progression rates to type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) and healthy controls.DesignSystematic review and meta-analysis.Data sourcesMedline and Embase between January 2000 and December 2019, studies published in English and conducted on humans.Eligibility criteria for selecting studiesObservational studies investigating progression to T2DM. Inclusion criteria were postpartum follow-up for at least 12 months, incident physician based diagnosis of diabetes, T2DM reported as a separate outcome rather than combined with impaired fasting glucose or impaired glucose tolerance, and studies with both a group of patients with GDM and a control group.ResultsThis meta-analysis of 20 studies assessed a total of 1 332 373 individuals (67 956 women with GDM and 1 264 417 controls). Data were pooled by random effects meta-analysis models, and heterogeneity was assessed by use of the I2 statistic. The pooled relative risk for the incidence of T2DM between participants with GDM and controls was estimated. Reasons for heterogeneity between studies were investigated by prespecified subgroup and meta-regression analyses. Publication bias was assessed by funnel plots and, overall, studies were deemed to have a low risk of bias (P=0.58 and P=0.90). The overall relative risk for T2DM was almost 10 times higher in women with previous GDM than in healthy controls (9.51, 95% confidence interval 7.14 to 12.67, P<0.001). In populations of women with previous GDM, the cumulative incidence of T2DM was 16.46% (95% confidence interval 16.16% to 16.77%) in women of mixed ethnicity, 15.58% (13.30% to 17.86%) in a predominantly non-white population, and 9.91% (9.39% to 10.42%) in a white population. These differences were not statistically significant between subgroups (white v mixed populations, P=0.26; white v non-white populations, P=0.54). Meta-regression analyses showed that the study effect size was not significantly associated with mean study age, body mass index, publication year, and length of follow-up.ConclusionsWomen with a history of GDM appear to have a nearly 10-fold higher risk of developing T2DM than those with a normoglycaemic pregnancy. The magnitude of this risk highlights the importance of intervening to prevent the onset of T2DM, particularly in the early years after pregnancy.Systematic review registrationPROSPERO CRD42019123079.

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A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses

10.1101/2020.08.31.275701 ◽

2020 ◽

Author(s):

Tiong Kit Tan ◽

Pramila Rijal ◽

Rolle Rahikainen ◽

Anthony H. Keeble ◽

Lisa Schimanski ◽

...

Keyword(s):

Antibody Response ◽

Receptor Binding ◽

Polyclonal Antibody ◽

Vaccine Candidate ◽

Binding Domain ◽

Antibody Responses ◽

Cold Chain ◽

Receptor Binding Domain ◽

Cell Infection ◽

Protein Receptor

ABSTRACTThere is dire need for an effective and affordable vaccine against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a modular virus-like particle vaccine candidate displaying the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) using SpyTag/SpyCatcher technology (RBD-SpyVLP). Low doses of RBD-SpyVLP in a prime-boost regimen induced a strong neutralising antibody response in mice and pigs that was superior to convalescent human sera. We evaluated antibody quality using ACE2 blocking and neutralisation of cell infection by pseudovirus or wild-type SARS-CoV-2. Using competition assays with a monoclonal antibody panel, we showed that RBD-SpyVLP induced a polyclonal antibody response that recognised all key epitopes on the RBD, reducing the likelihood of selecting neutralisation-escape mutants. The induction of potent and polyclonal antibody responses by RBD-SpyVLP provides strong potential to address clinical and logistic challenges of the COVID-19 pandemic. Moreover, RBD-SpyVLP is highly resilient, thermostable and can be lyophilised without losing immunogenicity, to facilitate global distribution and reduce cold-chain dependence.

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Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19

Nature Communications ◽

10.1038/s41467-020-19545-8 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Shidan Tosif ◽

Melanie R. Neeland ◽

Philip Sutton ◽

Paul V. Licciardi ◽

Sohinee Sarkar ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Family Members ◽

Antibody Responses ◽

Healthy Controls ◽

Serological Testing ◽

Igg Antibody ◽

Cytokine Responses ◽

Asymptomatic Infections ◽

Cellular Immune

Abstract Compared to adults, children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have predominantly mild or asymptomatic infections, but the underlying immunological differences remain unclear. Here, we describe clinical features, virology, longitudinal cellular, and cytokine immune profile, SARS-CoV-2-specific serology and salivary antibody responses in a family of two parents with PCR-confirmed symptomatic SARS-CoV-2 infection and their three children, who tested repeatedly SARS-CoV-2 PCR negative. Cellular immune profiles and cytokine responses of all children are similar to their parents at all timepoints. All family members have salivary anti-SARS-CoV-2 antibodies detected, predominantly IgA, that coincide with symptom resolution in 3 of 4 symptomatic members. Plasma from both parents and one child have IgG antibody against the S1 protein and virus-neutralizing activity detected. Using a systems serology approach, we demonstrate higher levels of SARS-CoV-2-specific antibody features of these family members compared to healthy controls. These data indicate that children can mount an immune response to SARS-CoV-2 without virological confirmation of infection, raising the possibility that immunity in children can prevent the establishment of SARS-CoV-2 infection. Relying on routine virological and serological testing may not identify exposed children, with implications for epidemiological and clinical studies across the life-span.

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Early Diagnosis and Treatment of Patients with Symptomatic Acute Q Fever Do Not Prohibit IgG Antibody Responses to Coxiella burnetii

Clinical and Vaccine Immunology ◽

10.1128/cvi.00322-12 ◽

2012 ◽

Vol 19 (10) ◽

pp. 1661-1666 ◽

Cited By ~ 8

Author(s):

C. C. H. Wielders ◽

L. M. Kampschreur ◽

P. M. Schneeberger ◽

M. M. Jager ◽

A. I. M. Hoepelman ◽

...

Keyword(s):

Early Diagnosis ◽

Phase I ◽

Phase Ii ◽

Coxiella Burnetii ◽

Q Fever ◽

Antibody Responses ◽

Igg Antibody ◽

Antibody Titers ◽

Acute Q Fever

ABSTRACTLittle is known about the effect of timing of antibiotic treatment on development of IgG antibodies following acute Q fever. We studied IgG antibody responses in symptomatic patients diagnosed either before or during development of the serologic response toCoxiella burnetii. Between 15 and 31 May 2009, 186 patients presented with acute Q fever, of which 181 were included in this retrospective study: 91 early-diagnosed (ED) acute Q fever patients, defined as negative IgM phase II enzyme-linked immunosorbent assay (ELISA) and positive PCR, and 90 late-diagnosed (LD) acute Q fever patients, defined as positive/dubious IgM phase II ELISA and positive immunofluorescence assay (IFA). Follow-up serology at 3, 6, and 12 months was performed using IFA (IgG phase I and II). High IgG antibody titers were defined as IgG phase II titers of ≥1:1,024 together with IgG phase I titers of ≥1:256. At 12 months, 28.6% of ED patients and 19.5% of LD patients had high IgG antibody titers (P= 0.17). No statistically significant differences were found in frequencies of IgG phase I and IgG phase II antibody titers at all follow-up appointments for adequately and inadequately treated patients overall, as well as for ED and LD patients analyzed separately. Additionally, no significant difference was found in frequencies of high antibody titers and between early (treatment started within 7 days after seeking medical attention) and late timing of treatment. This study indicates that early diagnosis and antibiotic treatment of acute Q fever do not prohibit development of the IgG antibody response.

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Titers, Prevalence, and Duration of SARS-CoV-2 Antibodies in a Local COVID-19 Outbreak and Following Vaccination

Vaccines ◽

10.3390/vaccines9060587 ◽

2021 ◽

Vol 9 (6) ◽

pp. 587

Author(s):

Jodi F. Hedges ◽

Macy A. Thompson ◽

Deann T. Snyder ◽

Amanda Robison ◽

Matthew P. Taylor ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Natural Infection ◽

Herd Immunity ◽

Antibody Responses ◽

Receptor Binding Domain ◽

Specific Antibodies ◽

Neutralization Capacity ◽

Protein Receptor ◽

Asymptomatic Infections ◽

Antibody Levels

Information concerning the development of neutralizing antibodies and their duration will be critical to establishing herd immunity for COVID-19. We sought to evaluate SARS-CoV-2 spike protein receptor-binding domain (RBD)-specific antibodies, their duration, and capacity for SARS-CoV-2 neutralization in volunteers while the pandemic spread within our community starting in March 2020. Those participants with the highest starting titers had the longest-lasting response, up to 12 months post-diagnosis. SARS-CoV-2 neutralization capacity was correlated with anti-RBD antibody levels. The majority of our participants with confirmed COVID-19 diagnosis had very mild or asymptomatic infections. We also detected low and largely non-neutralizing anti-RBD IgG titers in a few participants with no known COVID-19 diagnosis. Finally, we found that antibody responses induced by vaccination were significantly higher than those induced by natural infection. Thus, our study suggests that vaccination is still critical even for those naturally infected or diagnosed with COVID-19.

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Differences in IgG antibody responses following BNT162b2 and mRNA-1273 Vaccines

10.1101/2021.06.18.449086 ◽

2021 ◽

Author(s):

Jose Gilberto Montoya ◽

Amy E Adams ◽

Valerie Bonetti ◽

Sien Deng ◽

Nan A Link ◽

...

Keyword(s):

Protein Delivery ◽

Immunosuppressive Drugs ◽

Regression Modeling ◽

Antibody Responses ◽

Igg Antibody ◽

Mixed Effect ◽

S Protein ◽

For Profit ◽

Protein Receptor ◽

And Gender

Studies examining antibody responses by vaccine brand are lacking and may be informative for optimizing vaccine selection, dosage, and regimens. The purpose of this study is to assess IgG antibody responses following immunization with BNT162b2 (30 μg S protein) and mRNA-1273 (100 μg S protein) vaccines. A cohort of clinicians at a non-for-profit organization is being assessed clinically and serologically following immunization with BNT162b2 or mRNA-1273. IgG responses were measured at the Remington Laboratory by an IgG against the SARS-CoV-2 spike protein-receptor binding domain. Mixed-effect linear (MEL) regression modeling was used to examine whether the SARS-CoV-2 IgG level differed by vaccine brand, dosage, or days since vaccination. Among 532 SARS-CoV-2 seronegative participants, 530 (99.6%) seroconverted with either vaccine. After adjustments for age and gender MEL regression modeling revealed that the average IgG increased after the second dose compared to the first dose (p<0.001). Overall, titers peaked at week six for both vaccines. Titers were significantly higher for mRNA-1273 vaccine on days 14-20 (p < 0.05), 42-48 (p < 0.01), 70-76 (p < 0.05), 77-83 (p < 0.05), and higher for BNT162b2 vaccine on days 28-34 (p < 0.001). In two participants taking immunosuppressive drugs SARS-CoV-2 IgG remained negative. The mRNA-1273 vaccine elicited both earlier antibody responses than BNT162b2 and higher antibody levels, possibly due to the higher S-protein delivery. Prospective clinical and serological follow-up of defined cohorts such as this may prove useful in determining antibody protection and whether differences in antibody kinetics between the vaccines have clinical significance.

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A novel bivalent DNA vaccine encoding both spike protein receptor-binding domain and nucleocapsid protein of SARS-CoV-2 to elicit T cell and neutralising antibody responses that cross react with variants

10.1101/2021.06.18.448932 ◽

2021 ◽

Author(s):

Victoria A Brentville ◽

Mireille Vankemmelbeke ◽

Rachael L Methingham ◽

Peter Symonds ◽

Katherine W Cook ◽

...

Keyword(s):

T Cell ◽

Dna Vaccine ◽

Receptor Binding ◽

Binding Domain ◽

Antibody Responses ◽

Receptor Binding Domain ◽

Vaccine Platform ◽

Live Virus ◽

Cell Immunity ◽

Protein Receptor

The efficacy of vaccines targeting SARS-CoV-2 is becoming apparent now that the mRNA and adenovirus vector vaccines that have been approved for emergency use are showing promise. However, the longevity of the protective immune response and its efficacy against emerging variants remains to be determined. To improve longevity and future protection against variants, we have designed a DNA vaccine encoding both the SARS-CoV-2 spike (S) protein receptor-binding domain (RBD) and its nucleocapsid (N) protein, the latter of which is highly conserved amongst beta coronaviruses. The vaccine elicits strong pro-inflammatory CD4 Th1 and CD8 T-cell responses to both proteins, with these responses being significantly enhanced by fusing the nucleocapsid sequence to a modified Fc domain. We have shown that the vaccine also stimulates high titre antibody responses to RBD which efficiently neutralise in both a pseudotype and live virus neutralisation assay and show cross reactivity with S proteins from the emerging variants Alpha (B.1.1.7) and Beta (B.1.351). This DNA platform can be easily adapted to target variant RBD and N proteins and we show that a vaccine variant encoding the B.1.351 RBD sequence stimulates cross-reactive humoral and T-cell immunity. These data support the translation of this DNA vaccine platform into the clinic, thereby offering a particular advantage for targeting emerging SARS-CoV-2 variants.

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Immune responses to SARS-CoV-2 in children of parents with symptomatic COVID-19

10.21203/rs.3.rs-47021/v1 ◽

2020 ◽

Author(s):

Shidan Tosif ◽

Melanie Neeland ◽

Philip Sutton ◽

Paul Licciardi ◽

Sohinee Sarkar ◽

...

Keyword(s):

Immune Responses ◽

Chronic Exposure ◽

Family Members ◽

Asymptomatic Infection ◽

Antibody Responses ◽

Healthy Controls ◽

Serological Testing ◽

Igg Antibody ◽

Cytokine Responses ◽

Cellular Immune

Abstract Compared to adults, children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have mild or asymptomatic infection, but the underlying immunological differences remain unclear. We describe clinical features, virology, longitudinal cellular and cytokine immune profile, SARS-CoV-2-specific serology and salivary antibody responses in a family of two parents with PCR-confirmed symptomatic SARS-CoV-2 infection and their three children, who were repeatedly SARS-CoV-2 PCR negative. Cellular immune profiles and cytokine responses of all children were similar to their parents at all timepoints. All family members had salivary anti-SARS-CoV-2 antibodies detected, predominantly IgA, that coincided with symptom resolution in 3 of 4 symptomatic members. Plasma from both parents and one child had IgG antibody detected against the S1 protein and virus neutralising activity ranging from just detectable to robust titers. Using a systems serology approach, we show that all family members demonstrated higher levels of SARS-CoV-2-specific antibody features than healthy controls. These data indicate that children can mount an immune response to SARS-CoV-2 without virological evidence of infection. This raises the possibility that despite chronic exposure, immunity in children prevents establishment of SARS-CoV-2 infection. Relying on routine virological and serological testing may therefore not identify exposed children, with implications for epidemiological and clinical studies across the life-span.

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SARS-CoV-2 in pregnancy and possible transfer of immunity: assessment of peripartal maternal and neonatal antibody levels and a longitudinal follow-up

Journal of Perinatal Medicine ◽

10.1515/jpm-2021-0166 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Katharina Rathberger ◽

Sebastian Häusler ◽

Sven Wellmann ◽

Marco Weigl ◽

Florian Langhammer ◽

...

Keyword(s):

Antibody Response ◽

Respiratory Distress ◽

Receptor Binding Domain ◽

Specific Antibodies ◽

Protein Receptor ◽

Antibody Titers ◽

Antibody Levels ◽

Important Evidence ◽

In Pregnancy

Abstract Objectives In the current Severe Acute Respiratory Distress Coronavirus 2 (SARS-CoV-2) pandemic there is still great uncertainty about the effects of an infection in pregnancy especially regarding a possible fetal transmission of antibodies to SARS-CoV-2 and the longevity of this immunity. Methods Sixteen women who were infected with SARS-CoV-2 during pregnancy and their offspring were included. The antibody response to SARS-CoV-2 was measured in mother and umbilical cord blood peripartum and in a follow-up examination 6–11 weeks after birth. Medical history, symptoms regarding SARS-CoV-2, obstetric and neonatal information were queried following recommendations by the WHO. Results A total of 73% of the women and one third of the infants developed antibodies to SARS-CoV-2 spike (S) protein receptor binding domain (RBD), with a long interval between infection and birth proving favorable for a transplacentar transfer of antibodies to the neonates. All infants showed declining or vanishing antibody-titers in the follow-up examination, while the titers of their mothers were stable or even increased. Conclusions Our results demonstrate that transplacental transfer of SARS-CoV-2-specific antibodies is possible, but also indicate that the immunity that may be gained as a result might decrease in newborns postpartum. This provides important evidence that could be useful for further studies covering vaccination during pregnancy.

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