SARS-CoV-2 XBB.1.5 mRNA booster vaccination elicits limited mucosal immunity

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(770)

Published: Oct. 23, 2024

Current COVID-19 vaccines provide robust protection against severe disease but minimal acquisition of infection. Intramuscularly administered induce serum neutralizing antibodies (NAbs), their ability to boost mucosal immune responses remains be determined. In this study, we show that the XBB.1.5 messenger RNA (mRNA) boosters result in increased neutralization multiple acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants humans, including dominant circulating variant JN.1. contrast, found mRNA booster did not augment NAbs or IgA responses, although SARS-CoV-2 XBB infection substantially antibody responses. These data demonstrate current enhance peripheral do robustly increase Our highlight a separation between and systems humans emphasize importance developing next-generation immunity protect virus infections.

Language: Английский

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Neutrophil diversity and function in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Dec. 5, 2024

Abstract Neutrophils, the most abundant type of granulocyte, are widely recognized as one pivotal contributors to acute inflammatory response. Initially, neutrophils were considered mobile infantry innate immune system, tasked with immediate response invading pathogens. However, recent studies have demonstrated that versatile cells, capable regulating various biological processes and impacting both human health disease. Cytokines other active mediators regulate functional activity by activating multiple receptors on these thereby initiating downstream signal transduction pathways. Dysfunctions in disruptions neutrophil homeostasis been implicated pathogenesis numerous diseases, including cancer disorders, often due aberrant intracellular signaling. This review provides a comprehensive synthesis functions, integrating advancements this field. Moreover, it examines roles signaling pathways involved regulation activity. The pathophysiology diseases emerging therapeutic approaches targeting them also elaborated. addresses current limitations within field research, highlighting critical gaps knowledge warrant further investigation. In summary, seeks establish multidimensional model regulation, providing new perspectives for potential clinical applications research.

Language: Английский

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Repeated COVID-19 mRNA-based vaccination contributes to SARS-CoV-2 neutralizing antibody responses in the mucosa

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(770)

Published: Oct. 23, 2024

To prevent infection by respiratory viruses and consequently limit virus circulation, vaccines need to promote mucosal immunity. The extent which the currently used messenger RNA (mRNA)–based COVID-19 induce immunity remains poorly characterized. We evaluated neutralizing antibody responses in a cohort of 183 individuals. Participants were sampled at several time points after primary adenovirus vector–based or mRNA-based vaccination booster vaccinations. Our findings revealed that repeated with mRNA boosters promoted severe acute syndrome coronavirus 2 (SARS-CoV-2) antibodies nasal secretions. Nasal serum titers both IgG IgA isotypes correlated one another. investigated source these mouse model wherein mice received for SARS-CoV-2. These experiments indicated antibody–producing cells reside spleen bone marrow, whereas no proof tissue homing mucosa was observed, despite detection antibodies. Serum transfer confirmed circulating able migrate mucosa. Collectively, results demonstrate that, especially upon vaccination, can elicit might also stimulate induced previous SARS-CoV-2 infection. Moreover, migration be main mechanism. advance our understanding vaccine–induced have implications design vaccine strategies combat infections.

Language: Английский

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Passive infusion of an S2-Stem broadly neutralizing antibody protects against SARS-CoV-2 infection and lower airway inflammation in rhesus macaques

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(1), P. e1012456 - e1012456

Published: Jan. 23, 2025

The continued evolution of SARS-CoV-2 variants capable subverting vaccine and infection-induced immunity suggests the advantage a broadly protective against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from recovered-vaccinated donors neutralizing many other β-CoVs. Many these mAbs target conserved S2 stem region spike protein, rather than receptor binding domain contained within S1 primarily targeted by current vaccines. One S2-directed mAbs, CC40.8, has demonstrated efficacy in small animal models challenge. As next step pre-clinical testing as strategy to protect infection, we evaluated vivo CC40.8 clinically relevant non-human primate model conducting passive antibody transfer rhesus macaques (RM) followed mAb was intravenously infused at 10mg/kg, 1mg/kg, or 0.1 mg/kg into groups (n = 6) RM, alongside one group that received control (PGT121). Viral loads lower airway were significantly reduced animals receiving higher doses CC40.8. We observed significant reduction inflammatory cytokines macrophages with 10mg/kg 1mg/kg genome sequencing lack escape mutations epitope. Collectively, data demonstrate efficiency S2-targeting infection while providing critical preclinical work necessary for development pan–β-CoV

Language: Английский

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Neutralizing antibody responses to three XBB protein vaccines in older adults

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 2, 2025

Language: Английский

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Longitudinal analysis of antibody titers after primary and booster mRNA COVID-19 vaccination can identify individuals at risk for breakthrough infection

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Abstract A key issue in the post-COVID-19 era is ongoing administration of COVID-19 vaccines. Repeated vaccination essential for preparing against currently circulating and newly emerging SARS-CoV-2 variants while enabling people to continue with daily life. Optimizing strategies crucial efficiently manage medical resources establish an effective framework. Therefore, it important quantitatively understand vaccine-induced immunity dynamics be able identify poor responders lower sustained antibody titers as potential priorities revaccination. We investigated longitudinal titer data a cohort 2,526 Fukushima, Japan, from April 2021 November 2022 whom basic demographic health information was available. Using mathematical modeling machine learning, we stratified time-course patterns after 2 primary doses 1 booster dose mRNA identified 3 notable populations, which refer durable, vulnerable, rapid-decliner approximately half remained same population dose. Notably, experienced earlier infections than others. Furthermore, when comparing IgG(S) titers, IgA(S) T-spot counts between participants who breakthrough those did not, found that were significantly infected during early stage vaccination. Our computational approach adaptable various types vaccinations. This flexibility can inform policy decisions on vaccine distribution enhance both future pandemics era.

Language: Английский

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Mucosal and Systemic Antibody Responses After Boosting With a Bivalent Messenger RNA Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine

The Journal of Infectious Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Abstract Background Mucosal immunity plays a critical role in preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and replication. Understanding the capacity of disease 2019 (COVID-19) vaccines to elicit both mucosal systemic antibodies could help optimize vaccination strategies. Methods We conducted an open-label, phase 1/2 adaptive-design clinical trial evaluate safety immunogenicity COVID-19 immunizations. Healthy adults received priming doses mRNA-1273, booster dose second bivalent (WA-1 BA.4/BA.5) mRNA-1273.222. Adverse event data were collected. Serum evaluated. Results One hundred six persons enrolled. Thirty all 4 study-related vaccine doses. All well tolerated, with injection site pain, malaise, myalgias, headache being most frequently reported symptoms. Among those who booster, 24 30 (80%) had serological evidence SARS-CoV-2 infection. Following increases geometric mean binding pseudovirus neutralization antibody titers ancestral strain BA.1 BA.5 variants observed. Increases immunoglobulin G A (IgA) nasal salivary samples observed previously infected infection-naive participants, although prior markedly boosted virus-specific IgA responses. Conclusions The mRNA-1273.222 was safe immunogenic induced responses persons. Clinical Trials Registration NCT04889209.

Language: Английский

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Highly pure mRNA vaccine provides robust immunization against P. aeruginosa by minimizing type I interferon responses

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown, P. 113860 - 113860

Published: May 1, 2025

Language: Английский

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mRNA Technology and Mucosal Immunization

Vaccines, Journal Year: 2024, Volume and Issue: 12(6), P. 670 - 670

Published: June 17, 2024

Current mRNA vaccines are mainly administered via intramuscular injection, which induces good systemic immunity but limited mucosal immunity. Achieving through vaccination could diminish pathogen replication at the entry site and reduce interhuman transmission. However, delivering to mucosae faces challenges like degradation, poor into cells, reactogenicity. Encapsulating in extracellular vesicles may protect reactogenicity, making possible. Plant-derived from edible fruits have been investigated as carriers. Studies animals show that vehiculated orange-derived can elicit both immune responses when by oral, nasal, or routes. Once lyophilized, these products remarkable stability. The optimization of improve translation efficiency, immunogenicity, stability be obtained adjustments 5′cap region, poly-A tail, codons selection, use nucleoside analogues. Recent studies also proposed self-amplifying RNA containing an polymerase well circular constructs. Data parenterally primed demonstrate efficacy nasal immunization with non-adjuvanted protein, humans indicate combination a parenteral vaccine natural exposure same antigen provides protection reduces Hence, would beneficial least organisms pre-treated vaccines. This practice wide applications for treatment infectious diseases.

Language: Английский

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COVID-19 mRNA vaccines induce robust levels of IgG but limited amounts of IgA within the oronasopharynx of young children

The Journal of Infectious Diseases, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 7, 2024

Abstract Background Understanding antibody responses to SARS-CoV-2 vaccination is crucial for refining COVID-19 immunization strategies. Generation of mucosal immune responses, including IgA, could be potential benefit vaccine efficacy; however, limited evidence exists regarding the production antibodies following administration current mRNA vaccines young children. Methods We measured levels against from a cohort children under 5 years age (n = 24) undergoing (serially collected, matched serum and saliva samples) or in convenience sample presenting pediatric emergency department (nasal swabs, n 103). Furthermore, we assessed salivary nasal samples ability induce spike-mediated neutrophil extracellular traps (NET) formation. Results Longitudinal analysis post-vaccine revealed induction SARS-CoV-2–specific IgG but not IgA. Similarly, IgA was only observed obtained previously infected with without vaccination, vaccinated history infection. In addition, oronasopharyngeal prior infection were able trigger enhanced NET formation, played key role driving this process. Conclusions Despite specific oronasal mucosa, intramuscular have generate These results confirm independence systemic humoral suggest future strategies enhancing protection group.

Language: Английский

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