Next Generation Mucosal Vaccine Strategy for Respiratory Pathogens

Vaccines, Journal Year: 2023, Volume and Issue: 11(10), P. 1585 - 1585

Published: Oct. 12, 2023

Inducing humoral and cytotoxic mucosal immunity at the sites of pathogen entry has potential to prevent infection from getting established. This is different systemic vaccination, which protects against development symptoms. The field vaccination seen fewer technological advances compared nucleic acid subunit vaccine for injectable platforms. advent next-generation adenoviral vectors given a boost research. Basic research into mechanisms regulating innate adaptive discovery effective safe adjuvants will continue improve design. results clinical trials inhaled COVID-19 vaccines demonstrate their ability induce proliferation T cells production secreted IgA IgG antibodies locally, unlike intramuscular vaccinations. However, these immune responses par with review summarizes function respiratory mucosa-associated lymphoid tissue advantages that provide as

Language: Английский

---

Inhibition of the mitochondrial pyruvate carrier simultaneously mitigates hyperinflammation and hyperglycemia in COVID-19

Science Immunology, Journal Year: 2023, Volume and Issue: 8(82)

Published: Feb. 23, 2023

The relationship between diabetes and coronavirus disease 2019 (COVID-19) is bidirectional: Although individuals with high blood glucose (hyperglycemia) are predisposed to severe COVID-19, acute respiratory syndrome 2 (SARS-CoV-2) infection can also cause hyperglycemia exacerbate underlying metabolic syndrome. Therefore, interventions capable of breaking the network SARS-CoV-2 infection, hyperglycemia, hyperinflammation, all factors that drive COVID-19 pathophysiology, urgently needed. Here, we show genetic ablation or pharmacological inhibition mitochondrial pyruvate carrier (MPC) attenuates after influenza pneumonia. MPC using a second-generation insulin sensitizer, MSDC-0602K (MSDC), dampened pulmonary inflammation promoted lung recovery while concurrently reducing levels hyperlipidemia viral pneumonia in obese mice. Mechanistically, enhanced fitness destabilized hypoxia-inducible factor-1α, leading virus-induced inflammatory responses both murine human macrophages. We further showed MSDC nirmatrelvir (the antiviral component Paxlovid) provide protection against host development suppressed cellular autopsies, demonstrating its translational potential for treating COVID-19. Collectively, uncover pathway simultaneously modulates inflammation, tissue recovery, health, presenting synergistic therapeutic strategy treat particularly patients disease.

Language: Английский

---

COVID-19 mRNA Vaccines: Lessons Learned from the Registrational Trials and Global Vaccination Campaign

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 24, 2024

Our understanding of COVID-19 vaccinations and their impact on health mortality has evolved substantially since the first vaccine rollouts. Published reports from original randomized phase 3 trials concluded that mRNA vaccines could greatly reduce symptoms. In interim, problems with methods, execution, reporting these pivotal have emerged. Re-analysis Pfizer trial data identified statistically significant increases in serious adverse events (SAEs) group. Numerous SAEs were following Emergency Use Authorization (EUA), including death, cancer, cardiac events, various autoimmune, hematological, reproductive, neurological disorders. Furthermore, products never underwent adequate safety toxicological testing accordance previously established scientific standards. Among other major topics addressed this narrative review are published analyses harms to humans, quality control issues process-related impurities, mechanisms underlying (AEs), immunologic basis for inefficacy, concerning trends based registrational data. The risk-benefit imbalance substantiated by evidence date contraindicates further booster injections suggests that, at a minimum, should be removed childhood immunization program until proper studies conducted. Federal agency approval blanket-coverage population-wide had no support an honest assessment all relevant commensurate consideration risks versus benefits. Given extensive, well-documented unacceptably high harm-to-reward ratio, we urge governments endorse global moratorium modified questions pertaining causality, residual DNA, aberrant protein production answered.

Language: Английский

---

MSCs alleviate LPS-induced acute lung injury by inhibiting the proinflammatory function of macrophages in mouse lung organoid–macrophage model

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: March 11, 2024

Abstract Acute lung injury (ALI) is an inflammatory disease associated with alveolar injury, subsequent macrophage activation, cell infiltration, and cytokine production. Mesenchymal stem cells (MSCs) are beneficial for application in the treatment of diseases due to their immunomodulatory effects. However, mechanisms regulatory effects by MSCs on macrophages ALI need more in-depth study. Lung tissues were collected from mice mouse organoid construction. Alveolar (AMs) derived bronchoalveolar lavage interstitial (IMs) tissue co-cultured, novel matrigel-spreading organoids construct vitro model organoids–immune cells. Mouse compact bone-derived co-cultured organoids–macrophages confirm therapeutic effect acute injury. Changes transcriptome expression profile analyzed RNA sequencing. Well-established expressed various type-specific markers. grown spreading matrigel had property functional growing outside lumen. Lipopolysaccharide (LPS)-induced promoted chemotaxis toward enhanced inflammation-associated genes inflammation-injured compared controls. Treatment inhibited progress reduced levels components. Furthermore, through nuclear factor-κB pathway, MSC phenotypic transformation AMs modulated antigen-presenting function IMs, thereby affecting phenotype organoids. facilitate reception external stimuli construction models containing immune cells, which a potential research. exert protective against regulating different functions IMs lung, indicating mechanism intervention.

Language: Английский

---

mRNA vaccine designs for optimal adjuvanticity and delivery

RNA Biology, Journal Year: 2024, Volume and Issue: 21(1), P. 1 - 27

Published: March 26, 2024

Adjuvanticity and delivery are crucial facets of mRNA vaccine design. In modern vaccines, adjuvant functions integrated into nanoparticles, allowing the co-delivery antigen adjuvants in a unified, all-in-one formulation. this formulation, many vaccines utilize immunostimulating properties carrier components, including lipids polymers, as adjuvants. However, careful design is necessary, excessive adjuvanticity activation improper innate immune signalling can conversely hinder vaccination efficacy trigger adverse effects. also require systems to achieve expression antigen-presenting cells (APCs) within lymphoid organs. Some directly target APCs organs, while others rely on migration draining lymph nodes after taking up vaccines. This review explores current mechanistic understanding these processes ongoing efforts improve safety based understanding.

Language: Английский

---

Overview of mucosal immunity and respiratory infections in children: a focus on Africa

Current Opinion in Pediatrics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Given the substantial burden of respiratory tract infections (RTIs) on global paediatric health, enhancing our understanding mucosal immunity can help us advance biomarkers for diagnosis, prognosis and possible interventions in order to improve health outcomes. This review highlights critical role RTIs recent advances interventions, which offer promising strategies The significant growing interest advanced immune system protective against RTIs. Studies show that sub-Saharan Africa is disproportionately affected by with poverty-associated factors such as human immunodeficiency virus (HIV) malnutrition risk factors. Emerging evidence important microbiome innate adaptive responses has not only overall but also created opportunities RTI care through translation knowledge from these studies into diagnostics, therapeutics, vaccines.

Language: Английский

---

Recent advances in respiratory immunization: A focus on COVID-19 vaccines

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 355, P. 655 - 674

Published: Feb. 17, 2023

Language: Английский

---

A research and development (R&D) roadmap for broadly protective coronavirus vaccines: A pandemic preparedness strategy

Vaccine, Journal Year: 2023, Volume and Issue: 41(13), P. 2101 - 2112

Published: Feb. 21, 2023

Broadly protective coronavirus vaccines are an important tool for protecting against future SARS-CoV-2 variants and could play a critical role in mitigating the impact of outbreaks or pandemics caused by novel coronaviruses. The Coronavirus Vaccines Research Development (R&D) Roadmap (CVR) is aimed at promoting development such vaccines. CVR, funded Bill & Melinda Gates Foundation Rockefeller Foundation, was generated through collaborative iterative process, which led Center Infectious Disease Policy (CIDRAP) University Minnesota involved 50 international subject matter experts recognized leaders field. This report summarizes major issues areas research outlined CVR identifies high-priority milestones. covers 6-year timeframe organized into five topic areas: virology, immunology, vaccinology, animal human infection models, policy finance. Included each area key barriers, gaps, strategic goals, milestones, additional R&D priorities. roadmap includes 20 goals 86 26 ranked as high priority. By identifying issues, milestones addressing them, provides framework to guide funding campaigns that promote broadly

Language: Английский

---

Prevention of respiratory virus transmission by resident memory CD8+ T cells

Nature, Journal Year: 2023, Volume and Issue: 626(7998), P. 392 - 400

Published: Dec. 12, 2023

Language: Английский

---

Potential immune evasion of the severe acute respiratory syndrome coronavirus 2 Omicron variants

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 23, 2024

Coronavirus disease 2019 (COVID-19), which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a global pandemic. The Omicron variant (B.1.1.529) was first discovered in November 2021 specimens collected from Botswana, South Africa. become dominant worldwide, and several sublineages or subvariants have been identified recently. Compared to those of other mutants, most highly expressed amino acid mutations, with almost 60 mutations throughout genome, are spike (S) protein, especially receptor-binding domain (RBD). These increase binding affinity variants for ACE2 receptor, may also lead immune escape. Despite causing milder symptoms, epidemiological evidence suggests that exceptionally higher transmissibility, rates reinfection greater spread than prototype strain as well preceding variants. Additionally, overwhelming amounts data suggest levels specific neutralization antibodies against decrease vaccinated populations, although CD4 + CD8 T-cell responses maintained. Therefore, mechanisms underlying evasion still unclear. In this review, we surveyed current epidemic status potential escape Especially, focused on roles viral epitope antigenic drift, hybrid immunity, “original sin” mediating evasion. insights might supply more valuable concise information us understand spreading

Language: Английский

---