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Changes in the Immune Phenotype and Gene Expression Profile Driven by a Novel Tuberculosis Nanovaccine: Short and Long-Term Post-immunization.

ABSTRACT: Deciphering protection mechanisms against Mycobacterium tuberculosis (Mtb) remains a critical challenge for the development of new vaccines and therapies. We analyze the phenotypic and transcriptomic profile in lung of a novel tuberculosis (TB) nanoparticle-based boosting mucosal vaccine Nano-FP1, which combined to BCG priming conferred enhanced protection in mice challenged with low-dose Mtb. We analyzed the vaccine profile and efficacy at short (2 weeks), medium (7 weeks) and long term (11 weeks) post-vaccination, and compared it to ineffective Nano-FP2 vaccine. We observed several changes in the mouse lung environment by both nanovaccines, which are lost shortly after boosting. Additional boosting at long-term (14 weeks) recovered partially cell populations and transcriptomic profile, but not enough to enhance protection to infection. An increase in both total and resident memory CD4 and CD8 T cells, but no pro-inflammatory cytokine levels, were correlated with better protection. A unique gene expression pattern with differentially expressed genes revealed potential pathways associated to the immune defense against Mtb. Our findings provide an insight into the critical immune responses that need to be considered when assessing the effectiveness of a novel TB vaccine.

SUBMITTER: Martinez-Perez A

PROVIDER: S-EPMC7876410 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Changes in the Immune Phenotype and Gene Expression Profile Driven by a Novel Tuberculosis Nanovaccine: Short and Long-Term Post-immunization.

Martínez-Pérez Amparo A Igea Ana A Estévez Olivia O Ferreira Catarina M CM Torrado Egídio E Castro António Gil AG Fernández Carmen C Spetz Anna-Lena AL Adam Lucille L López González Moisés M Singh Mahavir M Reljic Rajko R González-Fernández África Á

Frontiers in immunology 20210128

Deciphering protection mechanisms against Mycobacterium tuberculosis (Mtb) remains a critical challenge for the development of new vaccines and therapies. We analyze the phenotypic and transcriptomic profile in lung of a novel tuberculosis (TB) nanoparticle-based boosting mucosal vaccine Nano-FP1, which combined to BCG priming conferred enhanced protection in mice challenged with low-dose Mtb. We analyzed the vaccine profile and efficacy at short (2 weeks), medium (7 weeks) ...[more]

PMID: 33584654

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Project description:BackgroundImpaired physical functional status is one of the typical long-term sequelae of COVID-19 infection that significantly affects the quality of life and work capacity. Minor changes in cardiac structure and function that are unable to cause the manifestation of overt heart failure may remain undetected in COVID-19 convalescents, at the same time potentially contributing to the persistence of symptoms and development of long COVID syndrome.PurposeTo study the typical features and short-term dynamics of cardiac remodeling and possible signs of cardiac dysfunction following hospitalization for COVID-19.MethodsThis is a combined cross-sectional and longitudinal cohort study in which 176 hospitalized patients (93 female and 83 male, mean age 53.4 ± 13.6 years) with COVID-19 infection underwent comprehensive transthoracic echocardiography pre-discharge (22.6 ± 7.1 days from the onset of symptoms) with repeated evaluation after 1 month. The control group included 88 age-, sex-, height- and weight-matched healthy individuals, with a subset of those (n = 53) matched to the subset of non-hypertensive study participants (n = 106).ResultsConcentric left ventricular geometry was revealed in 59% of participants, including 43% of non-hypertensive subjects; predominantly Grade I diastolic dysfunction was found in 35 and 25% of patients, respectively. Other findings were naturally following from described phenotype of the left venticle and included a mild increase in the absolute and relative wall thickness (0.45 ± 0.07 vs. 0.39 ± 0.04, p < 0.001), worsening of diastolic indices (e' velocity 9.2 ± 2.2 vs. 11.3 ± 2.6 cm/s, p < 0.001, E/e' ratio 7.5 ± 1.8 vs. 6.8 ± 1.7, p = 0.002) and global longitudinal strain (17.5 ± 2.4 vs. 18.6 ± 2.2, p < 0.001). No significant improvement was found on re-evaluation at 1 month.ConclusionsHospitalized patients recovering from COVID-19 were characterized by a high prevalence of left ventricular concentric remodeling, predominantly Grade I diastolic dysfunction, and a mild decrease in the longitudinal systolic function. These changes were less frequent but still prevalent in the non-hypertensive subgroup and largely persisted throughout the 1-month follow-up.

Project description:BACKGROUND:Kidney stone disease is common in industrialized countries. Recently, it has attracted growing attention, because of its significant association with adverse renal outcomes, including end stage renal disease. Calcium-containing kidney stones are frequent with high recurrence rates. While hypercalciuria is a well-known risk factor, restricted intake of animal protein and sodium, combined with normal dietary calcium, has been shown to be more effective in stone prevention compared with a low-calcium diet. Notably, the average sodium intake in Switzerland is twice as high as the WHO recommendation, while the intake of milk and dairy products is low. METHODS:We retrospectively analyzed Swiss recurrent kidney stone formers (rKSF) to test the impact of a low-sodium in combination with a low-calcium diet on the urinary risk profile. In patients with recurrent calcium oxalate containing stones, we investigated both, the consequence of a low-sodium diet on urinary volume and calcium excretion, and the influence of a low-sodium low-calcium diet on urinary oxalate excretion. RESULTS:Of the 169 patients with CaOx stones, 49 presented with hypercalciuria at baseline. The diet resulted in a highly significant reduction in 24-h urinary sodium and calcium excretion: from 201?±?89 at baseline to 128?±?88 mmol/d for sodium (p?<?0.0001), and from 5.67?±?3.01 to 4.06?±?2.46 mmol/d (p?<?0.0001) for calcium, respectively. Urine volume remained unchanged. Notably, no increase in oxalate excretion occurred on the restricted diet (0.39?±?0.26 vs 0.39?±?0.19 mmol/d, p?=?0.277). Calculated Psf (probability of stone formation) values were only predictive for the risk of calcium phosphate stones. CONCLUSION:A diet low in sodium and calcium in recurrent calcium oxalate stone formers resulted in a significant reduction of urinary calcium excretion, but no change in urine volume. In this population with apparently low intake of dairy products, calcium restriction does not necessarily result in increased urinary oxalate excretion. However, based on previous studies, we recommend a normal dietary calcium intake to avoid a potential increase in urinary oxalate excretion and unfavorable effects on bone metabolism in hypercalciuric KSFs.

Dataset Information

Changes in the Immune Phenotype and Gene Expression Profile Driven by a Novel Tuberculosis Nanovaccine: Short and Long-Term Post-immunization.

Publications

Changes in the Immune Phenotype and Gene Expression Profile Driven by a Novel Tuberculosis Nanovaccine: Short and Long-Term Post-immunization.

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