Sub-optimal neutralisation of omicron (B.1.1.529) variant by antibodies induced by vaccine alone or SARS-CoV-2 Infection plus vaccine (hybrid immunity) post 6-months
“…The antigen for anti-RBD IgG detection was designed on the basis of the ancestral strain. Although more than 30 amino acid mutations were detected in the omicron variant spike protein [16], our results showed that the anti-RBD IgG and neutralizing antibody tested by FRNT50 titers against the omicron variant provided a strong correlation, which is consistent with a previous report [17]. In addition, correlations between neutralizing activity against variants of SARS-CoV-2 and RBD-specific binding antibody have been reported in samples with high binding antibody titers [7].…”
This study examined the neutralizing activity and receptor binding domain (RBD) antibody levels against wild-type and omicron BA.1 and BA.2 variants in individuals who received three doses of COVID-19 vaccination. The relationship between the SARS-CoV-2 RBD antibody against wild-type and live virus neutralizing antibody titers against omicron BA.1 and BA.2 variants was examined. In total, 310 sera samples from individuals after booster vaccination (third dose) vaccination were tested for specific IgG wild-type SARS-CoV-2 RBD and the omicron BA.1 surrogate virus neutralization test (sVNT). The live virus neutralization assay against omicron BA.1 and BA.2 was performed using the foci-reduction neutralization test (FRNT50). The anti-RBD IgG strongly correlated with FRNT50 titers against BA.1 and BA.2. Non-linear regression showed that anti-RBD IgG with ≥148 BAU/mL and ≥138 BAU/mL were related to detectable FRNT50 titers (≥1:20) against BA.1 and BA.2, respectively. A moderate correlation was observed between the sVNT and FRNT50 titers. At detectable FRNT50 titers (≥1:20), the predicted sVNT for BA.1 and BA.2 were ≥10.57% and ≥11.52%, respectively. The study identified anti-RBD IgG and sVNT levels that predict detectable neutralizing antibodies against omicron variants. Assessment and monitoring of protective immunity support vaccine policies and will help identify optimal timing for booster vaccination.
“…The antigen for anti-RBD IgG detection was designed on the basis of the ancestral strain. Although more than 30 amino acid mutations were detected in the omicron variant spike protein [16], our results showed that the anti-RBD IgG and neutralizing antibody tested by FRNT50 titers against the omicron variant provided a strong correlation, which is consistent with a previous report [17]. In addition, correlations between neutralizing activity against variants of SARS-CoV-2 and RBD-specific binding antibody have been reported in samples with high binding antibody titers [7].…”
This study examined the neutralizing activity and receptor binding domain (RBD) antibody levels against wild-type and omicron BA.1 and BA.2 variants in individuals who received three doses of COVID-19 vaccination. The relationship between the SARS-CoV-2 RBD antibody against wild-type and live virus neutralizing antibody titers against omicron BA.1 and BA.2 variants was examined. In total, 310 sera samples from individuals after booster vaccination (third dose) vaccination were tested for specific IgG wild-type SARS-CoV-2 RBD and the omicron BA.1 surrogate virus neutralization test (sVNT). The live virus neutralization assay against omicron BA.1 and BA.2 was performed using the foci-reduction neutralization test (FRNT50). The anti-RBD IgG strongly correlated with FRNT50 titers against BA.1 and BA.2. Non-linear regression showed that anti-RBD IgG with ≥148 BAU/mL and ≥138 BAU/mL were related to detectable FRNT50 titers (≥1:20) against BA.1 and BA.2, respectively. A moderate correlation was observed between the sVNT and FRNT50 titers. At detectable FRNT50 titers (≥1:20), the predicted sVNT for BA.1 and BA.2 were ≥10.57% and ≥11.52%, respectively. The study identified anti-RBD IgG and sVNT levels that predict detectable neutralizing antibodies against omicron variants. Assessment and monitoring of protective immunity support vaccine policies and will help identify optimal timing for booster vaccination.
“…20,21 Yet, after the emergence of the omicron variants, neutralization antibody levels against omicron variant show 25.7-fold to 58.1-fold reduction in sera of healthy vaccinated subjects in comparison to wild-type. 22 Consequently, antibody levels that ensure neutralization, increased from >264 U/mL for alpha variant 8,9 to >2000 U/mL for omicron 16 , making the interpretation of antibody levels more difficult than before.…”
Background
Repeated vaccination against SARS-CoV-2 increases serological response in kidney transplant recipients (KTR) with high interindividual variability. No decision support tool exists to predict SARS-CoV-2 vaccination response in KTR.
Methods
We developed, internally and externally validated five different multivariable prediction models of serological response after the third and fourth vaccine dose against SARS-CoV-2 in KTR. Using 27 candidate predictor variables, we applied statistical and machine learning approaches including logistic regression (LR), LASSO-regularized LR, random forest, and gradient boosted regression trees. For development and internal validation, data from 585 vaccinations were used. External validation was performed in four independent, international validation datasets comprising 191, 184, 254, and 323 vaccinations, respectively.
Findings
LASSO-regularized LR performed on the whole development dataset yielded a 23- and 11-variable model, respectively. External validation showed AUC-ROC of 0.855, 0.749, 0.828, and 0.787 for the sparser 11-variable model, yielding an overall performance 0.819.
Interpretation
An 11-variable LASSO-regularized LR model predicts vaccination response in KTR with good overall accuracy. Implemented as an online tool, it can guide decisions when choosing between different immunization strategies to improve protection against COVID-19 in KTR.
“…Th1-dependent IgG1 vs . Th2-dependent IgG4 antibody subclasses were determined by ELISA as described previously 9 , 40 . Briefly, 96 well microtiter plates were coated with spike (S1) protein (SYNG-PRB026913, Syngene), at a concentration of 1 µg/ml, in PBS pH 7.4) and blocked with 1% BSA in PBS, pH 7.4.…”
Section: Methodsmentioning
confidence: 99%
“…Absorbance read at 450 nm. End point antibody titers determined and Th1:Th2 index was calculated as described previously 9 , 40 .…”
Section: Methodsmentioning
confidence: 99%
“…The emergence of SARS-CoV-2 variants of concern (VOCs) has raised concerns about the breadth and durability of neutralizing antibody responses 1 . Diminished vaccine effectiveness against VOCs such as Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529) has been reported for several authorised vaccines with two doses of vaccination 2 – 9 . With the potential of newly emergent highly transmissible VOCs, illustrated by the recent circulation of the Omicron variant 10 , understanding the persistence of neutralizing antibody responses against VOCs has become vital to assess the need for additional booster dose.…”
This is a comprehensive report on immunogenicity of COVAXIN® booster dose against ancestral and Variants of Concern (VOCs) up to 12 months. It is well known that neutralizing antibodies induced by COVID-19 vaccines wane within 6 months of vaccination leading to questions on the effectiveness of two-dose vaccination against breakthrough infections. Therefore, we assessed the persistence of immunogenicity up to 6 months after a two or three-dose with BBV152 and the safety of a booster dose in an ongoing phase 2, double-blind, randomized controlled trial (ClinicalTrials.gov: NCT04471519). We report persistence of humoral and cell mediated immunity up to 12 months of vaccination, despite decline in the magnitude of antibody titers. Administration of a third dose of BBV152 increased neutralization titers against both homologous (D614G) and heterologous strains (Alpha, Beta, Delta, Delta Plus and Omicron) with a slight increase in B cell memory responses. Thus, seronversion rate remain high in boosted recipients compared to non-booster, even after 6 months, post third dose against variants. No serious adverse events observed, except pain at the injection site, itching and redness. Hence, these results indicate that a booster dose of BBV152 is safe and necessary to ensure persistent immunity to minimize breakthrough infections of COVID-19, due to newly emerging variants.Trial registration: Registered with the Clinical Trials Registry (India) No. CTRI/2021/04/032942, dated 19/04/2021 and on Clinicaltrials.gov: NCT04471519.
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