International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 249, P. 125997 - 125997
Published: July 25, 2023
Language: Английский
The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 221(10)
Published: Sept. 6, 2024
Predicting the immunogenicity of candidate vaccines in humans remains a challenge. To address this issue, we developed lymphoid organ-chip (LO chip) model based on microfluidic chip seeded with human PBMC at high density within 3D collagen matrix. Perfusion SARS-CoV-2 spike protein mimicked vaccine boost by inducing massive amplification spike-specific memory B cells, plasmablast differentiation, and antibody secretion. Features tissue, including formation activated CD4+ T cell/B cell clusters emigration matured plasmablasts, were recapitulated LO chip. Importantly, myeloid cells competent capturing expressing mRNA vectored lipid nanoparticles, enabling assessment responses to vaccines. Comparison on-chip Wuhan monovalent Wuhan/Omicron bivalent boosts showed equivalent induction Omicron neutralizing antibodies, pointing immune imprinting as reported vivo. The thus represents versatile platform suited preclinical evaluation vaccine-boosting strategies.
Language: Английский
Citations
8
Viruses, Journal Year: 2024, Volume and Issue: 16(6), P. 900 - 900
Published: June 1, 2024
Currently, SARS-CoV-2 has evolved into various variants, including the numerous highly mutated Omicron sub-lineages, significantly increasing immune evasion ability. The development raises concerns about possibly diminished effectiveness of available vaccines and antibody-based therapeutics. Here, we describe those representative categories broadly neutralizing antibodies (bnAbs) that retain prominent against emerging variants sub-lineages. molecular characteristics, epitope conservation, resistance mechanisms these are further detailed, aiming to offer suggestion or direction for therapeutic antibodies, facilitate design with broad-spectrum potential.
Language: Английский
Citations
6
mBio, Journal Year: 2022, Volume and Issue: 13(4)
Published: July 28, 2022
According to the World Health Organization, COVID-19 may have caused ~15-million deaths across globe and is still ravaging world. Another wave of ~100 million infections predicted in United States due emergence highly transmissible immune-escaped Omicron variants.
Language: Английский
Citations
26
Microbiology Spectrum, Journal Year: 2022, Volume and Issue: 10(6)
Published: Oct. 11, 2022
Secretory immunoglobulin A (IgA) plays a crucial role in mucosal immunity for preventing the invasion of exogenous antigens; however, little is understood about neutralizing activity serum IgA. Here, to examine IgA antibodies against COVID-19 illnesses, we determined serum/plasma IgG and purified from previously SARS-CoV-2-infected mRNA vaccine-receiving individuals. We found that possesses substantial but rather modest SARS-CoV-2 compared with no significant correlation disease severity. Neutralizing achieved greatest at approximately 25 35 days after symptom onset, respectively. However, quickly diminished below detection limit 70 while was observed until 200 onset. The total sera/plasmas those largely correlated levels anti-SARS-CoV-2-S1-binding In individuals who were infected had detectable activity, single dose BNT162b2 or mRNA-1273 elicited potent serum/plasma-neutralizing second did not further strengthen neutralization antibody response. present data show systemic immune stimulation natural infection mRNA-vaccines elicits both SARS-CoV-2-specific responses serum, response diminishes faster than IMPORTANCE dimeric an important foreign objects by its on surfaces, monomeric thought relate phagocytic system activation. report novel coronavirus (COVID-19) developed (nIgG) (nIgA) active severe acute respiratory syndrome 2 (SARS-CoV-2). Although nIgA quick reached highest earlier nIgG response, activity. recovered vaccine Our study provides insights into kinetics pathogen naturally COVID-19-convalescent
Language: Английский
Citations
25
Cell Reports, Journal Year: 2023, Volume and Issue: 42(8), P. 112991 - 112991
Published: Aug. 1, 2023
Suboptimal responses to a primary vaccination course have been reported in the elderly, but there is little information regarding impact of age on booster third doses. Here, we show that individuals 70 years or older (median 73, range 70–75) who received two-dose schedule with AZD1222 and dose mRNA vaccine achieve significantly lower neutralizing antibody against SARS-CoV-2 spike pseudotyped virus compared those younger than 66, 54–69) at 1 month post booster. Impaired neutralization potency breadth elderly associated circulating "atypical" spike-specific B cells expressing CD11c FCRL5. However, when considering three doses vaccine, did not observe differences enrichment atypical cells. This work highlights finding AdV COVID-19 formats differentially instruct memory cell response.
Language: Английский
Citations
16
Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13
Published: Jan. 30, 2023
Intramuscularly administered vaccines stimulate robust serum neutralizing antibodies, yet they are often less competent in eliciting sustainable “sterilizing immunity” at the mucosal level. Our study uncovers a strong temporary component of immunity, emanating from intramuscular administration an mRNA vaccine. We show that saliva BNT162b2 vaccinees contains IgA targeting receptor-binding domain (RBD) severe acute respiratory syndrome coronavirus-2 spike protein and demonstrate these IgAs mediate neutralization. RBD-targeting were found to associate with secretory component, indicating their bona fide transcytotic origin polymeric multivalent nature. The mechanistic understanding high activity provided by IgA, acting first line defense, will advance vaccination design surveillance principles may point novel treatment approaches new routes vaccine boosting.
Language: Английский
Citations
15
PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(8), P. e1012383 - e1012383
Published: Aug. 2, 2024
The SARS-CoV-2 virus responsible for the COVID-19 global pandemic has exhibited a striking capacity viral evolution that drives continued evasion from vaccine and infection-induced immune responses. Mutations in receptor binding domain of S1 subunit spike glycoprotein have led to considerable escape antibody responses, reducing efficacy vaccines monoclonal (mAb) therapies. Therefore, there is need interrogate more constrained regions spike, such as S2 subdomain. Here, we present collection mAbs two convalescent individuals target multiple S2, including outside those commonly reported. One mAbs, C20.119, which bound highly conserved epitope fusion peptide, was able broadly neutralize across variants, SARS-CoV-1, closely related zoonotic sarbecoviruses. majority were non-neutralizing; however, many them could mediate antibody-dependent cellular cytotoxicity (ADCC) at levels similar S1-targeting mAb S309 previously authorized treatment infections. Several with ADCC function also trimers other human coronaviruses (HCoVs), MERS-CoV HCoV-HKU1. Our findings suggest can diverse epitopes functional HCoV sarbecovirus breadth likely functionally spike. These be developed potential future pandemics, while providing insight into ideal eliciting broad response.
Language: Английский
Citations
5
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2023, Volume and Issue: 1869(7), P. 166799 - 166799
Published: July 1, 2023
Language: Английский
Citations
13
Antiviral Research, Journal Year: 2024, Volume and Issue: 223, P. 105820 - 105820
Published: Feb. 1, 2024
The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) heavily burdened the entire world. Despite a prompt generation of vaccines and therapeutics to confront infection, virus remains threat. ancestor viral strain has evolved into several variants concern, with Omicron variant now having many distinct sublineages. Consequently, most available antibodies targeting spike went obsolete thus new therapies or therapeutic formats are needed. In this review we focus on antibody targets, provide an overview progress made so far, describe novel being explored, lessons learned from that can enhance preparedness.
Language: Английский
Citations
4
Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)
Published: July 22, 2024
Abstract The upper respiratory tract is the initial site of SARS-CoV-2 infection. Nasal spike-specific secretory immunoglobulin A (sIgA) correlates with protection against Omicron breakthrough We report that intranasal vaccination using human adenovirus serotype 5 (Ad5) vectored spike in people who previously vaccinated ancestral vaccine could induce robust neutralizing sIgA nasal passage. was predominantly present dimeric and multimeric forms accounted for nearly 40% total proteins mucosal lining fluids (NMLFs). low-level IgG also be detected NMLFs but not IgM, IgD, IgE. After a complete wash, passage replenished rapidly within few hours. comparison purified paired serum IgA, IgG, from same individuals showed up to 3-logs more potent than antibodies binding spikes subvariants. Serum IgA failed neutralize XBB BA.2.86, while retained neutralization these newly emerged variants. Further analysis effective or blocking spike-mediated cell-to-cell transmission protecting hACE2 mice challenge. Using monoclonal antibody as reference, we estimated contains about 2.6–3.9% collected approximately one month after vaccination. Our study provided insights developing vaccines can build an mutation-resistant first-line immune barrier constantly emerging
Language: Английский
Citations
4