Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection

Journal of Biomedical Science, Journal Year: 2022, Volume and Issue: 29(1)

Published: Jan. 4, 2022

The coronavirus disease 2019 (COVID-19) pandemic is an exceptional public health crisis that demands the timely creation of new therapeutics and viral detection. Owing to their high specificity reliability, monoclonal antibodies (mAbs) have emerged as powerful tools treat detect numerous diseases. Hence, many researchers begun urgently develop Ab-based kits for detection severe acute respiratory syndrome 2 (SARS-CoV-2) Ab drugs use COVID-19 therapeutic agents. detailed structure SARS-CoV-2 spike protein known, since this key infection, its receptor-binding domain (RBD) has become a major target development. Because RNA virus with mutation rate, especially under selective pressure aggressively deployed prophylactic vaccines neutralizing Abs, cocktails expected be important strategy effective treatment. Moreover, infection may stimulate overactive immune response, resulting in cytokine storm drives progression. Abs combat storms also been intense development treatments COVID-19. In addition drugs, are currently being utilized tests, including antigen immunoglobulin tests. Such tests crucial surveillance can used prevent spread Herein, we highlight some points regarding mAb-based pandemic.

Language: Английский

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SARS-CoV-2 breakthrough infections elicit potent, broad, and durable neutralizing antibody responses

Cell, Journal Year: 2022, Volume and Issue: 185(5), P. 872 - 880.e3

Published: Jan. 20, 2022

Although infections among vaccinated individuals lead to milder COVID-19 symptoms relative those in unvaccinated subjects, the specificity and durability of antibody responses elicited by breakthrough cases remain unknown. Here, we demonstrate that induce serum-binding -neutralizing are markedly more potent, durable, resilient spike mutations observed variants than subjects who received only 2 doses vaccine. However, show cases, were after infection, three times have serum-neutralizing activity comparable magnitude breadth, indicating an increased number exposures SARS-CoV-2 antigen(s) enhance quality responses. Neutralization SARS-CoV was moderate, however, underscoring importance developing vaccines eliciting broad sarbecovirus immunity for pandemic preparedness.

Language: Английский

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Large-Scale Study of Antibody Titer Decay following BNT162b2 mRNA Vaccine or SARS-CoV-2 Infection

Vaccines, Journal Year: 2021, Volume and Issue: 10(1), P. 64 - 64

Published: Dec. 31, 2021

Immune protection following either vaccination or infection with SARS-CoV-2 is thought to decrease over time. We designed a retrospective study, conducted at Leumit Health Services in Israel, determine the kinetics of IgG antibodies administration two doses BNT162b2 vaccine, unvaccinated individuals. Antibody titers were measured between 31 January 2021, and July 2021 mutually exclusive groups: (i) vaccinated individuals who received vaccine had no history previous COVID-19 (ii) convalescents not vaccine. A total 2653 fully by during study period 4361 convalescent patients included. Higher antibody observed (median 1581 AU/mL IQR [533.8-5644.6]) after second than 355.3 [141.2-998.7]; p < 0.001). In subjects, decreased up 38% each subsequent month while they less 5% per month. Six months 16.1% subjects levels below seropositivity threshold <50 AU/mL, only 10.8% 9 from infection. This demonstrates Pfizer-BioNTech mRNA have different compared been infected virus, higher initial but much faster exponential first group.

Language: Английский

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Efficient recall of Omicron-reactive B cell memory after a third dose of SARS-CoV-2 mRNA vaccine

Cell, Journal Year: 2022, Volume and Issue: 185(11), P. 1875 - 1887.e8

Published: April 8, 2022

Language: Английский

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Class switch toward noninflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination

Science Immunology, Journal Year: 2022, Volume and Issue: 8(79)

Published: Dec. 22, 2022

RNA vaccines are efficient preventive measures to combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. High levels of neutralizing SARS-CoV-2 antibodies an important component vaccine-induced immunity. Shortly after initial two mRNA vaccine doses, immunoglobulin G (IgG) response mainly consists proinflammatory subclasses IgG1 and IgG3. Here, we report that several months second vaccination, SARS-CoV-2–specific were increasingly composed noninflammatory IgG4, which further boosted by a third vaccination and/or variant breakthrough infections. IgG4 among all spike-specific IgG rose, on average, from 0.04% shortly 19.27% late vaccination. This induction was not observed homologous or heterologous with adenoviral vectors. Single-cell sequencing flow cytometry revealed substantial frequencies IgG4-switched B cells within spike-binding memory cell population [median 14.4%; interquartile range (IQR) 6.7 18.1%] compared overall repertoire (median 1.3%; IQR 0.9 2.2%) three immunizations. class switch associated reduced capacity mediate antibody-dependent cellular phagocytosis complement deposition. Because Fc-mediated effector functions critical for antiviral immunity, these findings may have consequences choice timing regimens using vaccines, including future booster immunizations against SARS-CoV-2.

Language: Английский

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Imprinted SARS-CoV-2-specific memory lymphocytes define hybrid immunity

Cell, Journal Year: 2022, Volume and Issue: 185(9), P. 1588 - 1601.e14

Published: March 17, 2022

Language: Английский

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Modeling of waning immunity after SARS-CoV-2 vaccination and influencing factors

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: March 28, 2022

Abstract SARS-CoV-2 vaccines are crucial in controlling COVID-19, but knowledge of which factors determine waning immunity is limited. We examined antibody levels and T-cell gamma-interferon release after two doses BNT162b2 vaccine or a combination ChAdOx1-nCoV19 for up to 230 days the first dose. Generalized mixed models with without natural cubic splines were used over time. Antibody responses influenced by infection, sex, age. IgA only became significant naturally infected. A one-year IgG projection suggested an initial two-phase response those given second dose delayed (ChAdOx1/BNT162b2) followed more rapid decrease levels. correlated significantly responses. Our results indicate that will drop at different rates depending on prior age, response, interval between injections. Only infection mounted lasting response.

Language: Английский

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Vaccination induces HIV broadly neutralizing antibody precursors in humans

Science, Journal Year: 2022, Volume and Issue: 378(6623)

Published: Dec. 1, 2022

Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled phase 1 clinical trial, the vaccine-priming candidate eOD-GT8 60mer adjuvanted with AS01

Language: Английский

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Potent cross-reactive antibodies following Omicron breakthrough in vaccinees

Cell, Journal Year: 2022, Volume and Issue: 185(12), P. 2116 - 2131.e18

Published: May 20, 2022

Highly transmissible Omicron variants of SARS-CoV-2 currently dominate globally. Here, we compare neutralization BA.1, BA.1.1, and BA.2. BA.2 RBD has slightly higher ACE2 affinity than BA.1 reduced by vaccine serum, possibly associated with its increased transmissibility. Neutralization differences between sub-lineages for mAbs (including therapeutics) mostly arise from variation in residues bordering the binding site; however, more distant mutations S371F (BA.2) R346K (BA.1.1) markedly reduce therapeutic antibody Vir-S309. In-depth structure-and-function analyses 27 potent RBD-binding isolated vaccinated volunteers following breakthrough Omicron-BA.1 infection reveals that they are focused two main clusters within RBD, right-shoulder antibodies showing prevalence. Selection somatic maturation have optimized potency less-mutated epitopes recovered highly mutated epitopes. All potently neutralize early pandemic strains, many show broad reactivity concern.

Language: Английский

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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Naturally Acquired Immunity versus Vaccine-induced Immunity, Reinfections versus Breakthrough Infections: A Retrospective Cohort Study

Clinical Infectious Diseases, Journal Year: 2022, Volume and Issue: 75(1), P. e545 - e551

Published: April 5, 2022

Abstract Background Waning of protection against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) conferred by doses the BNT162b2 vaccine begins shortly after inoculation and becomes substantial within 4 months. With that, impact prior on incident SARS-CoV-2 reinfection is unclear. Therefore, we examined long-term naturally acquired immunity (protection previous infection) compared to vaccine-induced immunity. Methods A retrospective observational study 124 500 persons, groups: (1) SARS-CoV-2-naive individuals who received a 2-dose regimen BioNTech/Pfizer mRNA vaccine, (2) previously infected have not been vaccinated. Two multivariate logistic regression models were applied, evaluating four SARS-CoV-2-related outcomes—infection, symptomatic disease (coronavirus 2019 [COVID-19]), hospitalization, death—between 1 June 14 August 2021, when Delta variant was dominant in Israel. Results vaccinees had 13.06-fold (95% confidence interval [CI], 8.08–21.11) increased risk for breakthrough unvaccinated-previously-infected individuals, first event (infection or vaccination) occurred during January February 2021. The significant as well. When allowing occur at any time between March 2020 evidence waning demonstrated, although naive still 5.96-fold CI: 4.85–7.33) 7.13-fold 5.51–9.21) disease. Conclusions Naturally confers stronger caused SARS-CoV-2, vaccine-indued

Language: Английский

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