Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients DOI Creative Commons
Matthias Becker, Anne Cossmann,

Karsten Lürken

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 6, 2022

Haemodialysis patients respond poorly to vaccination and continue be at-risk for severe COVID-19. Therefore, dialysis were among the first which a fourth COVID-19 was recommended. However, targeted information on how best maintain immune protection after SARS-CoV-2 vaccinations in groups remains limited. We provide, of our knowledge, time longitudinal response data controls triple BNT162b2 latter subsequent full-dose mRNA-1273. analysed systemic mucosal humoral IgG responses against receptor-binding domain (RBD) ACE2-binding inhibition towards variants concern including Omicron Delta with multiplex-based immunoassays. In addition, we assessed Spike S1-specific T-cell by interferon γ release assay. After vaccination, anti-RBD B.1 ACE2 binding reached peak levels patients, but remained inferior compared controls. Whilst detected B.1-specific 84% three doses, variant only detectable 38% samples declining 16% before vaccination. By using mRNA-1273 as dose, immunity all tested strongly augmented 80% having Omicron-specific inhibition. Modest declines second restored third dose significantly increased Our support current advice four-dose immunisation scheme individuals such haemodialysis patients. conclude that administration part mixed mRNA boost prevent could also beneficial other impaired individuals. Additionally, strategic application vaccine regimens may an immediate evasion potential.

Language: Английский

Exposure to BA.4/5 S protein drives neutralization of Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5 in vaccine-experienced humans and mice DOI Creative Commons
Alexander Muik, Bonny Gaby Lui,

Maren Bacher

et al.

Science Immunology, Journal Year: 2022, Volume and Issue: 7(78)

Published: Nov. 15, 2022

The SARS-CoV-2 Omicron variant and its sublineages show pronounced viral escape from neutralizing antibodies elicited by vaccination or prior infection owing to over 30-amino acid alterations within the spike (S) glycoprotein. Breakthrough of vaccinated individuals with BA.1 BA.2 is associated distinct patterns cross-neutralizing activity against variants concern (VOCs). In continuation our previous work, we characterized effect BA.4/BA.5 S glycoprotein exposure on antibody response upon breakthrough in variant-adapted booster mice. We found that immune sera triple mRNA-vaccinated subsequent during wave showed BA.1, BA.2, BA.2.12.1, itself. Administration a prototypic BA.4/BA.5-adapted mRNA vaccine mice after wild-type strain-based primary immunization broader than BA.1-adapted booster. Whereas bivalent format (wild-type + BA.1) broadens relative monovalent booster, cross-neutralization descendants more effective boosted vaccine. naïve mice, induces strong VOCs variants. These findings suggest that, when administered as boosters, mono- vaccines enhance neutralization breadth version also has potential confer protection no preexisting immunity SARS-CoV-2.

Language: Английский

Citations

28
Structural and functional characteristics of the SARS-CoV-2 Omicron subvariant BA.2 spike protein DOI
Jun Zhang, Weichun Tang, Hailong Gao

et al.

Nature Structural & Molecular Biology, Journal Year: 2023, Volume and Issue: 30(7), P. 980 - 990

Published: July 1, 2023

Language: Английский

Citations

21
Enhanced SARS-CoV-2 humoral immunity following breakthrough infection builds upon the preexisting memory B cell pool DOI
Timm Weber,

Sabrina Dähling,

S. Rose

et al.

Science Immunology, Journal Year: 2023, Volume and Issue: 8(89)

Published: Nov. 17, 2023

The human immune response must continuously adapt to newly emerging SARS-CoV-2 variants. To investigate how B cells respond repeated antigen exposure by Wu01 booster vaccination and Omicron breakthrough infection, we performed a molecular longitudinal analysis of the memory cell pool. We demonstrate that subsequent infection substantially increases frequency encoding SARS-CoV-2-neutralizing antibodies. However, this is not primarily attributable maturation, but selection preexisting clones. Moreover, broadly reactive arose early even neutralized highly mutated variants like XBB.1.5 individuals had encountered. Together, our data show immunity largely imprinted on over course multiple contacts can new through diversity.

Language: Английский

Citations

21
Somatic hypermutation introduces bystander mutations that prepare SARS-CoV-2 antibodies for emerging variants DOI Creative Commons
Michael Korenkov, Matthias Zehner, Hadas Cohen‐Dvashi

et al.

Immunity, Journal Year: 2023, Volume and Issue: 56(12), P. 2803 - 2815.e6

Published: Nov. 29, 2023

Language: Английский

Citations

19
Kaempferol inhibits SARS-CoV-2 invasion by impairing heptad repeats-mediated viral fusion DOI Creative Commons
Junwei Gao,

Can Cao,

Mingfei Shi

et al.

Phytomedicine, Journal Year: 2023, Volume and Issue: 118, P. 154942 - 154942

Published: June 24, 2023

The continuous evolution of SARS-CoV-2 has underscored the development broad-spectrum prophylaxis. Antivirals targeting membrane fusion process represent promising paradigms. Kaempferol (Kae), an ubiquitous plant flavonol, been shown efficacy against various enveloped viruses. However, its potential in anti-SARS-CoV-2 invasion remains obscure.To evaluate capabilities and mechanisms Kae preventing invasion.To avoid interference viral replication, virus-like particles (VLPs) constructed with luciferase reporter were applied. To investigate antiviral potency Kae, human induced pluripotent stem cells (hiPSC)-derived alveolar epithelial type II (AECII) ACE2 (hACE2) transgenic mice utilized as vitro vivo models, respectively. Using dual split protein (DSP) assays, inhibitory activities determined Alpha, Delta Omicron variants SARS-CoV-2, well SARS-CoV MERS-CoV. further reveal molecular determinants restricting fusion, synthetic peptides corresponding to conserved heptad repeat (HR) 1 2, involved mutant form HR2 explored by circular dichroism native polyacrylamide gel electrophoresis.Kae inhibited both vivo, which was mainly attributed suppressive effects on but not endocytosis, two pathways that mediate invasion. In accordance proposed model anti-fusion prophylaxis, functioned a pan-inhibitor including three emerged highly pathogenic coronaviruses, currently circulating BQ.1.1 XBB.1 SARS-CoV-2. Consistent typical target inhibitors, interacted HR regions S2 subunits. Distinct from previous prevent formation six-helix bundle (6-HB) competitively interacting HRs, deformed HR1 directly reacted lysine residues within region, latter considered critical for preservation stabilized during invasion.Kae prevents infection blocking possesses ability. These findings provide valuable insights into benefits Kae-containing botanical products complementary especially waves breakthrough infections re-infections.

Language: Английский

Citations

17
Plaque-neutralizing antibody to BA.2.12.1, BA.4 and BA.5 in individuals with three doses of BioNTech or CoronaVac vaccines, natural infection and breakthrough infection DOI Creative Commons
Samuel Cheng,

Chris KP Mok,

John KC Li

et al.

Journal of Clinical Virology, Journal Year: 2022, Volume and Issue: 156, P. 105273 - 105273

Published: Aug. 31, 2022

BA.2.12.1, BA.4 and BA.5 subvariants of SARS-CoV-2 variant-of-concern (VOC) Omicron (B.1.1.529) are spreading globally. They demonstrate higher transmissibility immune escape. Determine virus plaque reduction neutralization test (PRNT) antibody titres in individuals recently vaccinated with BNT162b2 (n = 20) or CoronaVac vaccines those convalescent from ancestral wild- type (WT) BA.2 infections 17) without 7) prior vaccination. Relative to the WT virus, had 4.8, 3.4, 4.6, 11.3 15.5-fold reductions geometric mean (GMT) BA.1, BA.2, viruses, respectively. Similarly, 8.0, 7.0, 11.8, 12.0 fold GMT two doses boosted by 6.1, 6.7, 6,3, 13.0 21.2 these Vaccinated breakthrough levels vs. (36.9) than unvaccinated (BA.4 8.2; 11.0). were less susceptible vaccine elicited BA.2.12.1. Nevertheless, three booster following detectable neutralizing responses while largely fail do so. led compared who vaccine-naive.

Language: Английский

Citations

27
Global Distribution, Dispersal Patterns, and Trend of Several Omicron Subvariants of SARS-CoV-2 across the Globe DOI Creative Commons
Ioannis Kopsidas, Sofia Karagiannidou, Evangelia Georgia Kostaki

et al.

Tropical Medicine and Infectious Disease, Journal Year: 2022, Volume and Issue: 7(11), P. 373 - 373

Published: Nov. 12, 2022

Our study aims to describe the global distribution and dispersal patterns of SARS-CoV-2 Omicron subvariants. Genomic surveillance data were extracted from CoV-Spectrum platform, searching for BA.1*, BA.2*, BA.3*, BA.4*, BA.5* variants by geographic region. BA.1* increased in November 2021 South Africa, with a similar increase across all continents early December 2021. did not reach 100% dominance continents. The spread first described differed greatly region, contrast which followed expansion, firstly occurring Asia subsequently Europe, Oceania, North America. BA.4* different pattern, where reached high proportions (maximum 60%) only Africa. is currently, Mid-August 2022, dominant strain, reaching almost continent aside Africa show increasing proportions, Asia, Americas, Oceania are following. emergence new depends mostly on their selective advantage, translated as enhanced transmissibility ability invade people existing immunity. Describing these useful better understanding epidemiology VOCs' transmission generating hypotheses about future emerging variants.

Language: Английский

Citations

25
SARS-CoV-2 spike-specific TFH cells exhibit unique responses in infected and vaccinated individuals DOI Creative Commons
Rongzhang He,

Xingyu Zheng,

Jian Zhang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Oct. 6, 2023

Long-term humoral immunity to SARS-CoV-2 is essential for preventing reinfection. The production of neutralizing antibody (nAb) and B cell differentiation are tightly regulated by T follicular help (T

Language: Английский

Citations

14
mRNA vaccines and hybrid immunity use different B cell germlines against Omicron BA.4 and BA.5 DOI Creative Commons
Emanuele Andreano, Ida Paciello, Giulio Pierleoni

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 28, 2023

Abstract Severe acute respiratory syndrome 2 Omicron BA.4 and BA.5 are characterized by high transmissibility ability to escape natural vaccine induced immunity. Here we test the neutralizing activity of 482 human monoclonal antibodies isolated from people who received two or three mRNA doses vaccinated after infection. The variants neutralized only approximately 15% antibodies. Remarkably, target mainly receptor binding domain Class 1/2, while infection recognize mostly 3 epitope region N-terminal domain. Different B cell germlines used analyzed cohorts. observation that vaccination hybrid immunity elicit a different against same antigen is intriguing its understanding may help design next generation therapeutics vaccines coronavirus disease 2019.

Language: Английский

Citations

13
Durable cross-protective neutralizing antibody responses elicited by lipid nanoparticle-formulated SARS-CoV-2 mRNA vaccines DOI Creative Commons
Ki Hyun Bae, Bhuvaneshwari D O Shunmuganathan, Li Zhang

et al.

npj Vaccines, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 23, 2024

Abstract The advent of SARS-CoV-2 variants with defined mutations that augment pathogenicity and/or increase immune evasiveness continues to stimulate global efforts improve vaccine formulation and efficacy. extraordinary advantages lipid nanoparticles (LNPs), including versatile design, scalability, reproducibility, make them ideal candidates for developing next-generation mRNA vaccines against circulating variants. Here, we assess the efficacy LNP-encapsulated booster encoding spike protein concern (Delta, Omicron) using a predecessor (YN2016C isolated from bats) strain elicit durable cross-protective neutralizing antibody responses. mRNA-LNP have desirable physicochemical characteristics, such as small size (~78 nm), low polydispersity index (<0.13), high encapsulation efficiency (>90%). We employ in vivo bioluminescence imaging illustrate capacity our LNPs induce robust expression secondary lymphoid organs. In BALB/c mouse model, three-dose subcutaneous immunization mRNA-LNPs achieved remarkably levels cross-neutralization Omicron B1.1.529 BA.2 extended periods time (28 weeks) good safety profiles all constructs when used regime, YN2016C bat virus sequences. These findings important implications design aim trigger immunity current newly emerging

Language: Английский

Citations

5