scholarly journals Serum anti-Spike antibody titers before and after heterologous booster with mRNA-1273 SARS-CoV-2 vaccine following two doses of inactivated whole-virus CoronaVac vaccine

Author(s):  
Robert Sinto ◽  
Dwi Utomo ◽  
Suwarti Suwarti ◽  
Erni J Nelwan ◽  
Henry Surendra ◽  
...  

Background: The inactivated whole-virus vaccine CoronaVac (SinoVac) is the COVID-19 vaccine most administered worldwide. However, data on its immunogenicity and reactogenicity to heterologous boosting with mRNA vaccines are lacking. Methods: In a cohort of hospital staff in Jakarta, Indonesia, who received two-dose CoronaVac six months prior (median 190 days, IQR165-232), we measured anti-Spike IgG titers on paired serum samples taken before and 28 days after a 100μg mRNA-1273 (Moderna) booster. We performed correlations and multivariable ordinal regressions. Findings: Among 304 participants, the median age was 31 years (range 21-59), 235 (77.3%) were women, 197 (64.8%) had one or more previous SARS-CoV-2 infections (including 155 [51.0%] who had a post-CoronaVac breakthrough infection. Pre-boost IgG titers correlated negatively with the time since the latest documented virus exposure (either by the second CoronaVac or SARS-CoV-2-infection whichever most recent). Previous SARS-CoV-2 infection and a longer time interval between second vaccine and mRNA-1273 boost were associated with a higher pre-boost IgG titer. Post-booster, the median IgG titer increased 9.3-fold, from 250 (IQR32-1389) to 2313 (IQR1226-4324) binding antibody units (BAU/mL) (p<0.001). All participants, including seven whose pre-boost IgG was below assay detection limits, became seropositive and all reached a substantial post-boost titer (≥364 BAU/mL). Post-boost IgG was not associated with pre-boost titer or previous SARS-CoV-2 infection. Booster reactogenicity was acceptable, with 7.9% of participants experiencing short-lived impairment of activities of daily living (ADL). Interpretation: A heterologous, high-dose mRNA-1273 booster after two-dose CoronaVac was highly immunogenic and safe, including in those most in need of improved immunity. Funding: Wellcome Trust, UK Keywords SARS-CoV-2; COVID-19; inactivated vaccine; CoronaVac; mRNA-1273; antibodies

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Kathryn McGuckin Wuertz ◽  
Erica K. Barkei ◽  
Wei-Hung Chen ◽  
Elizabeth J. Martinez ◽  
Ines Lakhal-Naouar ◽  
...  

AbstractThe emergence of SARS-CoV-2 variants of concern (VOC) requires adequate coverage of vaccine protection. We evaluated whether a SARS-CoV-2 spike ferritin nanoparticle vaccine (SpFN), adjuvanted with the Army Liposomal Formulation QS21 (ALFQ), conferred protection against the Alpha (B.1.1.7), and Beta (B.1.351) VOCs in Syrian golden hamsters. SpFN-ALFQ was administered as either single or double-vaccination (0 and 4 week) regimens, using a high (10 μg) or low (0.2 μg) dose. Animals were intranasally challenged at week 11. Binding antibody responses were comparable between high- and low-dose groups. Neutralizing antibody titers were equivalent against WA1, B.1.1.7, and B.1.351 variants following two high dose vaccinations. Dose-dependent SpFN-ALFQ vaccination protected against SARS-CoV-2-induced disease and viral replication following intranasal B.1.1.7 or B.1.351 challenge, as evidenced by reduced weight loss, lung pathology, and lung and nasal turbinate viral burden. These data support the development of SpFN-ALFQ as a broadly protective, next-generation SARS-CoV-2 vaccine.


2007 ◽  
Vol 53 (2) ◽  
pp. 241-250 ◽  
Author(s):  
William CS Cho ◽  
Timothy TC Yip ◽  
Roger KC Ngan ◽  
Tai-Tung Yip ◽  
Vladimir N Podust ◽  
...  

Abstract Background: We previously used ProteinChip array profiling analysis to discover a serum biomarker associated with nasopharyngeal carcinoma (NPC). In this study, we used the same method to examine other biomarkers associated with NPC and response to chemotherapy (CT) in NPC patients. Methods: We performed ProteinChip array analysis in 209 serum samples from 66 relapsed patients before and after salvage CT with gemcitabine and cisplatin or etoposide and cisplatin combinations, 11 patients in remission, and 35 healthy individuals. Intensities of the biomarker peaks were correlated with CT response of the patients and other clinical parameters. Results: We discovered 13 candidate biomarkers associated with different clinical parameters. Two biomarkers (2803 and 3953 Da) were significantly increased in patients compared with controls at all stages of disease. Analysis of pre- and post-CT paired serum samples revealed 7 biomarkers correlated with impact of CT. Of these 7 biomarkers, 2 (2509 and 2756 Da) were significantly increased and 5 (7588, 7659, 7765, 7843, and 8372 Da) were significantly decreased post-CT in either 1 or both CT cohorts. Four biomarkers from pre-CT sera were correlated with CT response, with 3 (2950, 13 510, and 14 855 Da) being significantly decreased and 1 (6701 Da) significantly increased in patients who did not respond to CT. Tandem mass spectrometric sequencing and/or immunoaffinity capture assay identified the 3953 Da biomarker as a fragment of interα-trypsin inhibitor precursor and 7765 Da biomarker as platelet factor-4. Conclusions: Treatment-associated serum biomarkers found might serve to triage NPC patients for appropriate CT treatment.


2013 ◽  
Vol 59 (4) ◽  
pp. 658-666 ◽  
Author(s):  
Yang Luo ◽  
Cheng Wang ◽  
Xi Chen ◽  
Tianying Zhong ◽  
Xiaoyi Cai ◽  
...  

BACKGROUND MicroRNAs (miRNAs) are present in body fluids and may have the potential to serve as disease biomarkers. This study explored the clinical value of miRNAs in serum and urine as biomarkers for idiopathic childhood nephrotic syndrome (NS). METHODS We obtained serum samples from 159 NS children (24 steroid resistant and 135 steroid sensitive), 109 age/sex-matched healthy controls and 44 children with other kidney diseases. Serum miRNAs were analyzed with the TaqMan Low Density Array and then validated with a quantitative reverse-transcription PCR assay with 126 individual samples. Moreover, we collected paired serum samples from 50 patients before and after treatment to determine the value of these miRNAs for condition assessment. In addition, urine samples from these patients were examined for candidate miRNAs. RESULTS The concentrations of serum miR-30a-5p, miR-151-3p, miR-150, miR-191, and miR-19b were highly increased in NS children compared with controls (P &lt; 0.0001). The urinary miR-30a-5p concentration was also increased in NS (P = 0.001). The area under the ROC curve and the odds ratio for the combined 5 serum miRNAs were 0.90 (95% CI, 0.86–0.94; P &lt; 0.0001) and 40.7 (95% CI, 6.06–103; P &lt; 0.0001), respectively. Moreover, the concentrations of the 5 serum miRNAs and urinary miR-30a-5p markedly declined with the clinical improvement of the patients. CONCLUSIONS We determined that 5 distinct serum miRNAs and urinary miR-30a-5p were increased in NS children. These circulating or urinary miRNAs may represent potential diagnostic and prognostic biomarkers for idiopathic pediatric NS.


Author(s):  
Nishanth Parameswaran ◽  
Oriol Mitjà ◽  
Christian Bottomley ◽  
Cynthia Kwakye ◽  
Wendy Houinei ◽  
...  

WHO and its partners aim to interrupt yaws transmission in endemic countries and to certify others as being yaws-free. Transmission can be assessed using rapid plasma reagin (RPR) tests, reflecting current or recent infection, but RPR is operationally impractical. We evaluated changes in antibody levels against two recombinant treponemal antigens, rp17 (also known as Tp17) and TmpA, after antibiotic treatment given as part of a randomized controlled trial for yaws in Ghana and Papua New Guinea. Paired serum samples from children aged 6–15 years with confirmed yaws, collected before and after treatment, were tested for antibodies to rp17 and TmpA using a semi-quantitative bead-based immunoassay. Of 344 baseline samples, 342 tested positive for anti-rp17 antibodies and 337 tested positive for anti-TmpA antibodies. Six months after treatment, the median decrease in anti-rp17 signal was 3.2%, whereas the median decrease in anti-TmpA was 53.8%. The magnitude of change in the anti-TmpA response increased with increasing RPR titer fold-change. These data demonstrate that responses to TmpA decrease markedly within 6 months of treatment whereas (as expected) those to rp17 do not. Incorporating responses to TmpA as a marker of recent infection within an integrated sero-surveillance platform could provide a way to prioritize areas for yaws mapping.


2021 ◽  
Author(s):  
Kathryn McGuckin Wuertz ◽  
Erica Barkei ◽  
Wei-hung Chen ◽  
Elizabeth J. Martinez ◽  
Ines Elakhal Naouar ◽  
...  

The emergence of SARS-CoV-2 variants of concern (VOC) requires adequate coverage of vaccine protection. We evaluated whether a spike ferritin nanoparticle vaccine (SpFN), adjuvanted with the Army Liposomal Formulation QS21 (ALFQ), conferred protection against the B.1.1.7 and B.1.351 VOCs in Syrian golden hamsters. SpFN-ALFQ was administered as either single or double-vaccination (0 and 4 week) regimens, using a high (10 μg) or low (0.2 μg) immunogen dose. Animals were intranasally challenged at week 11. Binding antibody responses were comparable between high- and low-dose groups. Neutralizing antibody titers were equivalent against WA1, B.1.1.7, and B.1.351 variants following two high dose two vaccinations. SpFN-ALFQ vaccination protected against SARS-CoV-2-induced disease and viral replication following intranasal B.1.1.7 or B.1.351 challenge, as evidenced by reduced weight loss, lung pathology, and lung and nasal turbinate viral burden. These data support the development of SpFN-ALFQ as a broadly protective, next-generation SARS-CoV-2 vaccine.


2020 ◽  
Author(s):  
Maurizio Ruscio ◽  
Elisa D’Agnolo ◽  
Anna Belgrano ◽  
Mario Plebani ◽  
Giuseppe Lippi

AbstractBackgroundThe approach to diagnosing, treating and monitoring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection relies strongly on laboratory resources, with serological testing representing the mainstay for studying the onset, nature and persistence of humoral immune response. This study was aimed at evaluating the analytical performance of the novel Beckman Coulter anti-SARS-CoV-2 IgG chemiluminescent immunoassay.MethodsThis analytical assessment encompassed the calculation of intra-assay, inter-assay and total imprecision, linearity, limit of blank (LOB), limit of detection (LOD), functional sensitivity, and comparison of anti-SARS-CoV-2 antibodies values obtained on paired serum samples using DiaSorin Liaison SARS-CoV-2 S1/S2 IgG and Roche Elecsys Anti-SARS-CoV-2 total antibodies. Diagnostic performance was also tested against results of molecular testing on nasopharyngeal swabs, collected over the previous 4 months.ResultsIntra-assay, inter-assay and total imprecision of Beckman Coulter anti-SARS-CoV-2 IgG were between 4.3-4.8%, 2.3-3.9% and 4.9-6.2%, respectively. The linearity of the assay was excellent between 0.11-18.8 antibody titers. The LOB, LOD and functional sensitivity were 0.02, 0.02 and 0.05, respectively. The diagnostic accuracy (area under the curve; AUC) of Beckman Coulter anti-SARS-CoV-2 IgG compared to molecular testing was 0.87 (95% CI, 0.84-0.91; p<0.001) using manufacturer’s cut-off, and increased to 0.90 (95% CI, 0.86-0.94; p<0.001) with antibody titers. The AUC was non-significantly different from that of Roche Elecsys Anti-SARS-CoV-2, but was always higher than that of DiaSorin Liaison SARS-CoV-2 S1/S2 IgG. The correlation of Beckman Coulter Access SARS-CoV-2 IgG was 0.80 (95% CI, 0.75-0.84; p<0.001) with Roche Elecsys Anti-SARS-CoV-2 and 0.72 (95% CI, 0.66-0.77; p<0.001) with DiaSorin Liaison SARS-CoV-2 S1/S2 IgG, respectively.ConclusionsThe results of this analytical evaluation of Beckman Coulter Access anti-SARS-CoV-2 IgG suggests that this fully-automated chemiluminescent immunoassay represents a valuable resource for large and accurate seroprevalence surveys.


Author(s):  
Sara Pasqualetti ◽  
Dominika Szőke ◽  
Mauro Panteghini

AbstractBackground:Pneumatic tube transportation (PTT) may induce hemolysis (H) in blood samples. We aimed to compare the H degree before and after PTT implementation in our hospital.Methods:Hemolysis indices (HI) for all lithium-heparin plasma samples (P) drawn by the Emergency Department in 2-month periods were retrospectively collected and pre- (n=3579) and post-PTT (n=3469) results compared. The impact of PTT introduction was investigated on LDH [HI threshold (HIt), 25], conjugated bilirubin (cBIL) (HIt, 30), K (HIt, 100) and ALT (HIt, 125). In addition, HI retrieved for P and paired serum samples collected in silica clot activator tubes (S) from the same venipuncture were compared in pre- (n=501) and post-PTT (n=509) periods.Results:Median (5–95th percentile) HI in P was significantly higher in post-PTT period [7 (0–112) vs. 6 (0–82), p<0.001]. Results reported as ‘Hemolysis’ in P increased from 6.6% in pre-PTT to 9.4% in post-PTT (p<0.001). Investigated tests gave the following rejection rates (pre-PTT vs. post-PTT): LDH, 13.4% vs. 18.8%, p<0.001; cBIL, 9.4% vs. 27.0%, p<0.05; K, 3.7% vs. 5.6%, p<0.001; ALT, 2.9% vs. 4.4%, p<0.01. The slightly higher susceptibility to H of S compared to paired P found in the pre-PTT [9 (1–64) vs. 6 (0–85)] was not confirmed in the post-PTT period [7 (0–90) vs. 8 (1–72)], in which median HI in S was significantly lower (p<0.001) than in pre-PTT.Conclusions:In our setting PTT promotes H in P, increasing the rate of rejected tests. The use of S appears to protect against the hemolysing effect of PTT.


Author(s):  
Seri Jeong ◽  
Nuri Lee ◽  
Su Kyung Lee ◽  
Eun-Jung Cho ◽  
Jungwon Hyun ◽  
...  

Reliable results of serologic positivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody before and after AstraZeneca (AZ) vaccination are essential to estimate the efficacy of vaccination. We assessed the positivity rates and associated factors using five SARS-CoV-2 antibody assays. A total of 228 paired serum samples (456 samples) were obtained from 228 participants. After baseline sampling, the second sampling was conducted between 11-28 days after the first dose of AZ. Sera were tested using five SARS-CoV-2 antibody assays, including two surrogate virus neutralization tests. A questionnaire on symptom, severity, and duration of adverse reactions was completed by all participants. The overall positive rates for SARS-CoV-2 antibody were 84.6% for Roche, 92.5% for Abbott, 75.4% for Siemens, 90.7% for SD Biosensor, and 66.2% for GenScript assays after the first dose of AZ vaccination. The positive rates and antibody titer of sera obtained between 21-28 days were significantly higher than those obtained between 11-20 days in all five assays. More severe and longer duration of adverse reactions were related to higher SARS-CoV-2 antibody levels. The agreements and correlations among the applied assays were substantial (к=0.73-0.95) and strong (ρ=0.83-0.91). A single dose of AZ vaccination led to high positivity rates based on the five assays. Days after vaccination and adverse reactions could help estimate serologic conversions. The results should be interpreted cautiously considering the applied assays and cutoffs. Our findings could inform decisions regarding vaccination and laboratory settings and, thus, contribute to the control of the spread of SARS-CoV-2 infection.


Author(s):  
Seri Jeong ◽  
Nuri Lee ◽  
Su Kyung Lee ◽  
Eun-Jung Cho ◽  
Jungwon Hyun ◽  
...  

Reliable results for serologic positivity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody after the second dose of AstraZeneca (AZ) vaccination are important to estimate the real efficacy of vaccination. We evaluated the positivity rates and the changes of semi-quantitative antibody titers before and after the first and second ChAdOx1 nCoV-19 Vaccinations using five SARS-CoV-2 antibody assays, including two surrogate virus neutralization tests. A total of 674 serum samples were obtained from 228 participants during three blood sampling periods. A questionnaire on symptoms, severity and adverse reactions duration was completed after the second vaccination. The overall positive rates for all assays were 0.0-0.9% before vaccination, 66.2-92.5% after the first vaccination, and 98.2-100.0% after the second vaccination. Median antibody titers in five assays after the second dose of vaccination were increased compared to those after the first dose (106.4-fold increase for Roche total antibody, 3.6-fold for Abbott IgG, 3.6-fold for Siemens, 1.2-fold for SD Biosensor V1 neutralizing antibody, and 2.2-fold for GenScript neutralizing antibody). Adverse reactions reduced after the second dose in 89.9% of participants compared to after the first dose. Overall, the second vaccination led to almost 100% positivity rates based on these SARS-CoV-2 antibody assays. The results should be interpreted with caution, considering the characteristics of applied assays. Our findings could inform decisions regarding vaccination and the use of immunoassays, thus, contributing to the SARS-CoV-2 pandemic control.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Adriana Luchs

AbstractInvestigation of human enterovirus (EV) in diarrheic fecal specimens is valuable to address EV diversity circulating worldwide. However, the detection of EV strains exclusively in fecal specimens must be interpreted cautiously. EV are well known causative agents associated with a spectrum of human diseases, but not acute gastroenteritis. EV isolation in stool samples could not necessarily be associated with diarrheic symptoms, as most EV infections appear to be asymptomatic, and healthy children could excrete EV in their stool. The diagnostic of EV is only confirmed when the neutralization test presents a significant increase in antibody titers (three times or more) in the paired serum samples (acute-phase and convalescent-phase) against the same EV serotype isolated in feces. In addition, patients suffering from acute gastroenteritis, even during an EV investigation, must be screened in parallel for gastroenteric viruses (i.e. norovirus and rotavirus) in order to clarify if the symptoms could be linked to other viral agent detected in their fecal samples. Surveillance of EV diversity among distinct patient groups, including diarrheic individuals, must be taken into consideration and can considerably increase the power of non-polio EV surveillance system in Brazil. More well-designed studies are necessary to further elucidate the role of EV in acute gastroenteritis.


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