Exploring new perspectives in immunology

Cell, Journal Year: 2024, Volume and Issue: 187(9), P. 2079 - 2094

Published: April 1, 2024

Several conceptual pillars form the foundation of modern immunology, including clonal selection theory, antigen receptor diversity, immune memory, and innate control adaptive immunity. However, some immunological phenomena cannot be explained by current framework. Thus, we still do not know how to design vaccines that would provide long-lasting protective immunity against certain pathogens, why autoimmune responses target antigens others, or response infection sometimes does more harm than good. Understanding these mysteries may require question existing assumptions develop test alternative explanations. Immunology is increasingly at a point when, once again, exploring new perspectives becomes necessity.

Language: Английский

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SARS-CoV-2 correlates of protection from infection against variants of concern

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(10), P. 2805 - 2812

Published: July 26, 2024

Language: Английский

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Mucosal unadjuvanted booster vaccines elicit local IgA responses by conversion of pre-existing immunity in mice

Nature Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: May 13, 2025

Abstract Mucosal delivery of vaccine boosters induces robust local protective immune responses even without any adjuvants. Yet, the mechanisms by which antigen alone mucosal immunity in respiratory tract remain unclear. Here we show that an intranasal booster with unadjuvanted recombinant SARS-CoV-2 spike protein, after intramuscular immunization 1 μg mRNA–LNP encoding full-length protein (Pfizer/BioNTech BNT162b2), elicits retooling lymph node-resident cells. On boosting, peripheral node-primed B cells rapidly migrated to lung through CXCR3–CXCL9 and CXCR3–CXCL10 signaling differentiated into antigen-specific IgA-secreting plasma Memory CD4 + T served as a natural adjuvant for developing IgA inducing expression chemokines CXCL9 CXCL10 memory cell recruitment. Furthermore, CD40 TGFβ had important roles development. Repeated boosting amplified anamnestic both upper lower tracts. These findings help explain why nasal do not require induce at mucosa can be used design safe effective vaccines against pathogens.

Language: Английский

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Progress and challenges in the clinical evaluation of immune responses to respiratory mucosal vaccines

Expert Review of Vaccines, Journal Year: 2024, Volume and Issue: 23(1), P. 362 - 370

Published: March 6, 2024

Following the coronavirus disease pandemic, respiratory mucosal vaccines that elicit both and systemic immune responses have garnered increasing attention. However, human physiological characteristics pose significant challenges in evaluation of immunity, which directly impedes development application vaccines.

Language: Английский

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Early, robust mucosal secretory IgA but not IgG response to SARS-CoV-2 spike in oral fluid is associated with faster viral clearance and COVID-19 symptom resolution.

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

Published: Sept. 12, 2024

Abstract Background Efforts are underway to support the development of novel mucosal coronavirus disease 2019 (COVID-19) vaccines. However, there is limited consensus about complementary role immunity in progression and how evaluate immunogenicity This study investigated oral antibody responses viral clearance COVID-19 symptom duration. Methods Participants with polymerase chain reaction (PCR)–confirmed severe acute respiratory syndrome 2 (SARS-CoV-2) infection provided fluid for testing SARS-CoV-2 multiplex assays, nasal swabs reverse-transcription PCR, information at up 8 follow-ups from April 2020 February 2022. Results High moderate anti-spike (S) secretory IgA (SIgA) postinfection was associated significantly faster resolution across age groups effect sizes equivalent prior vaccine time infection. Those high anti-S SIgA cleared virus 14 (95% confidence interval [CI], 10–18) days recovered 9–10 CI, 6–14) earlier. Delayed higher IgG longer recovery. Experiencing symptoms >4 weeks lower anti–receptor-binding domain 15–30 after onset (P < .001). Conclusions Robust early appears recovery symptoms. research underscores importance harmonizing immune response assays new

Language: Английский

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Single MVA-SARS-2-ST/N Vaccination Rapidly Protects K18-hACE2 Mice against a Lethal SARS-CoV-2 Challenge Infection

Viruses, Journal Year: 2024, Volume and Issue: 16(3), P. 417 - 417

Published: March 8, 2024

The sudden emergence of SARS-CoV-2 demonstrates the need for new vaccines that rapidly protect in case an emergency. In this study, we developed a recombinant MVA vaccine co-expressing prefusion-stabilized spike protein (ST) and nucleoprotein (N, MVA-SARS-2-ST/N) as approach to further improve vaccine-induced immunogenicity efficacy. Single MVA-SARS-2-ST/N vaccination K18-hACE2 mice induced robust protection against lethal respiratory challenge infection 28 days later. protective outcome correlated with activation SARS-CoV-2-neutralizing antibodies (nABs) substantial amounts SARS-CoV-2-specific T cells especially lung MVA-SARS-2-ST/N-vaccinated mice. Emergency just 2 before resulted delayed onset clinical disease these increased titers nAB or spleen lung. These data highlight potential multivalent COVID-19 S- N-protein, which contributes development strategies emerging pathogens.

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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Bacterial lysates in modifying sIgA levels in the upper respiratory tract in COVID-19 patients

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 10, 2025

A great deal of evidence has accumulated suggesting an important role mucosal immunity not only in preventing COVID-19 but also the pathogenesis this infection. The aim study was to evaluate levels secretory immunoglobulin (sIgA) different compartments upper respiratory tract patients relation severity disease and treatment with a bacteria-based immunomodulating agent (Immunovac VP4). titers sIgA were determined by ELISA nasal epithelial swabs, pharyngeal salivary gland secretions at baseline on days 14 30 treatment. nasal, significantly lower more severe (subgroup A) than less B), p < 0.01. In subgroup A, who received Immunovac VP4 had higher convalescent period those did receive therapy 0.05. B patients, increase observed from day whether they add-on or not, On treatment, standard group, however, decreased, while receiving maintained high levels, Oxygen saturation increased both groups, 0.001. However, it group Thus, addition bacterial lysate-based regimen for moderate-to-severe induces production sIgA. SIgA is inversely correlated CRP percentage lung involvement CT scan directly SpO2 levels.

Language: Английский

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Epidemiology and Mortality Risk of Severe Viral Pneumonia During the Pre-Pandemic, COVID-19 Pandemic and Post-Pandemic Era: A Retrospective Study of Hospitalized Children in ShenZhen, China Between 2017 and 2023

Journal of Epidemiology and Global Health, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 3, 2025

This study aims to investigate the spectrum of viruses leading severe viral pneumonia (SVP) and associated risk factors for mortality among pediatric patients in intensive care unit (PICU). Taking outbreak end COVID-19 pandemic as a aboundary, The pre-pandemic period spans from 01/2017 12/2019, 01/2020 12/2021, post-pandemic 01/2022 12/2023. Patients were subsequently stratified into survivor non-survivor groups based on clinical outcomes. A total 1007 (median age 1.42 years, range 0.58-4.00; male: female ratio 1.7:1) diagnosed with SVP. Cases (n = 419, 41.6%), 272, 27.0%), 316, 31.4%) periods. Viral predominance varied across phases: Pre-pandemic: Influenza (IVA, 37.0% [155/419]), respiratory syncytial virus (RSV, 29.8%), adenovirus (19.8%), influenza B (15.5%). Pandemic phase: Human rhinovirus (HRV, 40.1% [109/272]), RSV (33.1%), parainfluenza (11.4%), bocavirus (HBoV, 10.7%). Post-pandemic: HRV (24.4% [77/316]), (22.8%), HBoV (14.2%), IVA (13.6%). Comparative analysis revealed significant intergroup differences proportion aged < 3 primary immunodeficiency disorders (PIDs), sepsis between pure infection deaths coinfection-associated fatalities SVP cases. Logistic regression identified eight independent predictors: acute leukemia, other malignant tumors, PIDs, moderate-to-severe underweight, rhabdomyolysis, distress syndrome (ARDS), infection-related encephalopathy, multiorgan dysfunction (MODS). prediction model demonstrated robust discriminative capacity mortality: sensitivity 73.8%, specificity 90.2%, AUC 0.888 (95%CI 0.838-0.938) via ROC curve analysis. has altered landscape causing children. presence underlying health conditions, particularly malignancies, immunodeficiency, significantly increases death children pneumonia. offers reliable tool practice predict these patients.

Language: Английский

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Hypertonic intranasal vaccines gain nasal epithelia access to exert strong immunogenicity

Mucosal Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Intranasal vaccines potentially offer superior protection against viral infections compared with injectable vaccines. The immunogenicity of intranasal including adenovirus vector (AdV), has room for improvement, while few options are available safe execution. In this study, we demonstrate that modifying a basic parameter vaccine formulation, i.e., osmolarity, can significantly enhance the Addition glycerol to AdV solutions, unlike other viscous additives, enhanced systemic and mucosal antibodies as well resident memory T cells in nasal tissues, which could protect tissue lungs influenza virus. While not prolong retention solutes, it promoted infection epithelial by facilitating access cell. was induced hypertonicity preparations sodium chloride, glucose, mannitol demonstrated capacity immunogenicity. Moreover, hypertonic adjuvanted subunit vaccines, but without adjuvant or Overall, delivery be improved through simple approach, resulting stronger certain

Language: Английский

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