Project description:IntroductionThe U.S. lags in the nationwide implementation of primary prevention interventions that have been shown to be efficacious. However, the potential population health benefit of widespread implementation of these primary prevention interventions remains unclear.MethodsThe meta-analytic literature from October 2013 to March 2014 of primary prevention interventions published between January 2000 and March 2014 was reviewed. The authors then estimated the number of deaths that could have been averted in the U.S. in 2010 if all rigorously studied, efficacious primary prevention interventions for which population attributable risk proportions could be estimated were implemented nationwide.ResultsA total of 372,054 (15.1%) of all U.S. deaths in 2010 would have been averted if all rigorously studied, efficacious primary prevention interventions were implemented. Two in three averted deaths would have been from cardiovascular disease or malignancy.ConclusionsA substantial proportion of deaths in the U.S. in 2010 could have been averted if efficacious primary prevention interventions were implemented nationwide. Further investment in the implementation of efficacious interventions is warranted to maximize population health in the U.S.

| S-EPMC5512568 | biostudies-literature

Persistent epigenetic memory of SARS-CoV-2 mRNA vaccination in monocyte-derived macrophages

Project description:Immune memory plays a critical role in the development of durable antimicrobial immune responses. How precisely mRNA vaccines train innate immune cells to shape protective host defence mechanisms remains unknown. Here we show that SARS-CoV-2 mRNA vaccination significantly establishes histone H3 lysine 27 acetylation (H3K27ac) at promoters of human monocyte-derived macrophages, suggesting epigenetic memory. However, we found that two consecutive vaccinations were required for persistence of H3K27ac, which matched with proinflammatory innate immune-associated transcriptional changes and antigen-mediated cytokine secretion. H3K27ac at promoter regions were preserved for six months and a single mRNA booster vaccine potently restored their levels and release of macrophage-derived cytokines. Interestingly, we found that H3K27ac at promoters is enriched for G-quadruplex DNA secondary structure-forming sequences in macrophage-derived nucleosome-depleted regions, linking epigenetic memory to nucleic acid structure. Collectively, these findings reveal that mRNA vaccines induce a highly dynamic and persistent training of innate immune cells enabling a sustained pro-inflammatory immune response.

| S-SCDT-10_1038-S44320-025-00093-6 | biostudies-other

Gene expression on SARS CoV-2 specific CD8 T cells after SARS CoV-2 vaccination

Project description:We studied the impact of a vaccine prime dose on CD8 T cell gene expression We first immunized mice with an Ad5-SARS CoV-2 spike vaccine and then evaluated gene expression on SARS CoV-2 specific CD8 T cells at week 4.

2021-08-11 | GSE173567 | GEO

Spleen tyrosine kinase mediates innate and adaptive immune crosstalk in SARS-CoV-2 mRNA vaccination

Project description:Durable cell-mediated immune responses require efficient innate immune signaling and the release of pro-inflammatory cytokines. How precisely mRNA vaccines trigger innate immune cells for shaping antigen specific adaptive immunity remains unknown. Here we show that SARS-CoV-2 mRNA vaccination primes human monocyte derived macrophages for activation of the NLRP3 inflammasome. Spike protein exposed macrophages undergo NLRP3 driven pyroptotic cell death and subsequently secrete mature interleukin-1β. These effects depend on activation of spleen tyrosine kinase (SYK) coupled to C-type lectin receptors. Using autologous co-cultures, we show that SYK and NLRP3 orchestrate macrophage driven activation of effector memory T cells. Furthermore, vaccination induced macrophage priming can be enhanced with repetitive antigen exposure providing a rationale for prime-boost concepts to augment innate immune signaling in SARS-CoV-2 vaccination. Collectively, these findings identify SYK as a regulatory node capable of differentiating between primed and unprimed macrophages, which modulate spike protein specific T cell responses.

| S-SCDT-EMM-2022-15888P | biostudies-other

Structures from "Engineering Neutralizing SARS-CoV Antibodies to Bind SARS-CoV-2"

Project description: Not available

| S-BSST379 | biostudies-other

ACE2, Much More Than Just a Receptor for SARS-COV-2.

Project description:The rapidly evolving pandemic of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection worldwide cost many lives. The angiotensin converting enzyme-2 (ACE-2) has been identified as the receptor for the SARS-CoV-2 viral entry. As such, it is now receiving renewed attention as a potential target for anti-viral therapeutics. We review the physiological functions of ACE2 in the cardiovascular system and the lungs, and how the activation of ACE2/MAS/G protein coupled receptor contributes in reducing acute injury and inhibiting fibrogenesis of the lungs and protecting the cardiovascular system. In this perspective, we predominantly focus on the impact of SARS-CoV-2 infection on ACE2 and dysregulation of the protective effect of ACE2/MAS/G protein pathway vs. the deleterious effect of Renin/Angiotensin/Aldosterone. We discuss the potential effect of invasion of SARS-CoV-2 on the function of ACE2 and the loss of the protective effect of the ACE2/MAS pathway in alveolar epithelial cells and how this may amplify systemic deleterious effect of renin-angiotensin aldosterone system (RAS) in the host. Furthermore, we speculate the potential of exploiting the modulation of ACE2/MAS pathway as a natural protection of lung injury by modulation of ACE2/MAS axis or by developing targeted drugs to inhibit proteases required for viral entry.

| S-EPMC7294848 | biostudies-literature

Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination in mouse models.

Project description:BackgroundVaccines in emergency use are efficacious against COVID-19, yet vaccine-induced prevention against nasal SARS-CoV-2 infection remains suboptimal.MethodsSince mucosal immunity is critical for nasal prevention, we investigated the efficacy of an intramuscular PD1-based receptor-binding domain (RBD) DNA vaccine (PD1-RBD-DNA) and intranasal live attenuated influenza-based vaccines (LAIV-CA4-RBD and LAIV-HK68-RBD) against SARS-CoV-2.FindingsSubstantially higher systemic and mucosal immune responses, including bronchoalveolar lavage IgA/IgG and lung polyfunctional memory CD8 T cells, were induced by the heterologous PD1-RBD-DNA/LAIV-HK68-RBD as compared with other regimens. When vaccinated animals were challenged at the memory phase, prevention of robust SARS-CoV-2 infection in nasal turbinate was achieved primarily by the heterologous regimen besides consistent protection in lungs. The regimen-induced antibodies cross-neutralized variants of concerns. Furthermore, LAIV-CA4-RBD could boost the BioNTech vaccine for improved mucosal immunity.InterpretationOur results demonstrated that intranasal influenza-based boost vaccination induces mucosal and systemic immunity for effective SARS-CoV-2 prevention in both upper and lower respiratory systems.FundingThis study was supported by the Research Grants Council Collaborative Research Fund, General Research Fund and Health and Medical Research Fund in Hong Kong; Outbreak Response to Novel Coronavirus (COVID-19) by the Coalition for Epidemic Preparedness Innovations; Shenzhen Science and Technology Program and matching fund from Shenzhen Immuno Cure BioTech Limited; the Health@InnoHK, Innovation and Technology Commission of Hong Kong; National Program on Key Research Project of China; donations from the Friends of Hope Education Fund; the Theme-Based Research Scheme.

| S-EPMC8687884 | biostudies-literature

An ounce of prevention is better : Monitoring wildlife health as a tool for pandemic prevention.

Project description: Not available

| S-EPMC11239677 | biostudies-literature