Pathogens and Immunity最新文献

Background: Circulating degranulated platelets have been described during acute SARS-CoV-2 infection and associated with COVID-19 complications. This study investigated the relationship between the presence of plasma SARS-CoV-2 RNA (ie, SARS-CoV-2 RNAemia), systemic inflammation, and platelet dysfunction in a group of patients with COVID-19. Unlike our previous publication, which focused on platelet characterization, this work explores potential determinants of platelet activation, based on a distinct subset of patients with available stored samples.

Methods: Patients with COVID-19 were stratified by platelet δ-granule content using the luciferin/luciferase assay into 2 groups: normal (COV_δ-norm) and low (COV_δ-low). Plasma SARS-CoV-2 RNAemia (RT-qPCR), cytokines, and chemokines (Cytometric Bead Array) were quantified on plasma samples. Markers of platelet activation were measured by flow cytometry in whole blood.

Results: A total of 75 patients with COVID-19 were enrolled; 57 presented normal levels of platelet δ-granule content (COV_δ-norm) and 18 had low levels of platelet δ-granules (COV_δ-low). Groups were comparable in terms of age, sex, comorbidities, and SARS-CoV-2 RNAemia levels. Patients in the COV_δ-low group showed significantly higher chemokine and cytokine levels compared to those in the COV_δ-norm group, with strong correlations between IL-6, as well as granulocyte-macrophage colony-stimulating factor (GM-CSF), with platelet degranulation parameters. A similar trend, albeit less pronounced, was observed when patients were stratified based on their platelet activation phenotype.

Conclusions: These findings suggest that peripheral inflammation, rather than SARS-CoV-2 RNAemia, is associated with platelet dysfunction during acute SARS-CoV-2 infection.

Background: Despite the control of Bordetella pertussis with vaccine introduction, the incidence of pertussis has increased in the United States and globally. New vaccine strategies are clearly needed to regain control of this vaccine-preventable infection.

Methods: Experimental pertussis infection of baboons induces an acute respiratory illness with clinical and laboratory features similar to whooping cough in man. In a previous study, acellular pertussis-vaccinated (aP) baboons were protected from clinical illness but not from prolonged airway colonization. In contrast, convalescent baboons are protected from both clinical illness and colonization. These studies suggest that current aP vaccines may be ineffective at preventing airway colonization, contributing to resurgence of pertussis.

Results: In studies conducted at the University of Massachusetts Chan Medical School in Worcester, Massachusetts, mucosal IgG antibody responses in nasopharyngeal washes are similar in convalescent and vaccinated baboons. However, significantly higher mucosal anti-pertussis immunoglobulin A (IgA) responses are observed in convalescent animals.

Conclusions: These studies suggest that mucosal IgA responses to some pertussis antigens will result in bacterial clearance.

Background: Maternal immunization provides vaccine-specific immunity to the infant via breast milk. Multiple studies have reported the presence of SARS-CoV-2 antibodies in human breast milk (HBM) from infected and/or vaccinated women. However, there is limited information on the analytical performance, consistency, and quality of the methods used. Standardized and rigorous assays are needed to meet clinical study endpoints and for comparisons across studies.

Methods: We optimized high-throughput multiplex immunoassays for quantification of SARS-CoV-2 immunoglobulin (Ig)G and IgA in HBM and determined antibody levels in HBM samples from 236 SARS-CoV-2 vaccinated (infected and non-infected) and 50 pre-pandemic (unexposed) lactating women. Additionally, SARS-CoV-2 neutralizing activity was examined in a subset of 75 SARS-CoV-2 HBM from vaccinated (infected and non-infected) women using live virus focus reduction neutralization and pseudovirus assays. Concordance between SARS-CoV-2 binding and live virus neutralization outcomes was examined.

Results: The multiplex SARS-CoV-2 assays had adequate analytical sensitivity, repeatability, precision, and assay linearity and were reliable for quantification of IgG and IgA in HBM. Positivity thresholds for Spike- and Nucleocapsid-specific IgG and IgA were established; IgG discriminated positive/negative SARS-CoV-2-immune HBM with high sensitivity and specificity, while IgA reactivity overlapped. A strong correlation was observed between live SARS-CoV-2 and pseudovirus neutralization activity. HBM Spike IgA and neutralization titers were highly correlated.

Conclusions: SARS-CoV-2 binding and neutralizing antibody activity in HBM was determined using standardized and rigorous assays. HBM positivity cutoff values for SARS-CoV-2 vaccination and infection were established. The methods and approach described here could be applied to other pathogens and mucosal secretions.

Background: The dissemination of highly pathogenic avian influenza (HPAI) A(H5N1) in US poultry and dairy cows poses a public health threat. Farm workers caring for infected animals are at risk to acquire infections due to exposure to contaminated milk or poultry feces and secretions. Far ultraviolet-C (UV-C) light could provide continuous decontamination of surfaces and air in agricultural settings, but efficacy against organisms in whole milk or chicken manure is unclear.

Methods: We examined the efficacy of far UV-C light against bacteriophage MS2 and methicillin-resistant Staphylococcus aureus (MRSA) in phosphate-buffered saline (PBS), 5% fetal calf serum, whole milk, or 5%, 10%, and 25% chicken manure, both in liquid suspension and dried on surfaces. We also compared the efficacy of 300 mJ/cm² doses of far UV-C and 254-nm UV-C light against the test organisms in liquid droplets or droplets dried on surfaces.

Results: For both test organisms, far UV-C achieved significantly smaller log₁₀ reductions in whole milk and in chicken manure suspensions than in PBS or 5% fetal calf serum, both in liquid suspension and when dried on surfaces (P<0.0001). In whole milk, average reductions of both organisms with all doses were ≤1.2 log₁₀ in liquid suspensions and ≤2.4 log₁₀ when dried on surfaces. We found 254-nm UV-C was significantly more effective in reducing MRSA and MS2 dried on surfaces in whole milk or in 10% chicken manure (P≤0.02) but not in liquid droplets (P>0.05) except 5% chicken manure (P<0.001).

Conclusions: Our results suggest that in the absence of prior cleaning and disinfection far UV-C and 254-nm UV-C light technologies may have limited efficacy as an adjunctive method to reduce the risk for transmission of HPAI from surfaces in high-risk settings on farms.

Background: Prior infection with SARS-CoV-2 has been reported to confer protection against reinfections. Because Peru has been affected by several variants of this virus, it is an ideal location to better explore this phenomenon. In this study, we aim to evaluate protection of prior SARS-CoV-2 infection against reinfection by variants during the COVID-19 pandemic in Peru.

Methods: A nested case-control study was carried out, using national data from Peru between 2021 and 2023. Five study periods were defined, delimited by the predominance of the main SARS-CoV-2 variants circulating during the pandemic. Cases were paired with controls in a 1 to 4 rate by sex, age, region, being a health worker, and the week of infection. Protection was calculated using conditional logistic regression to estimate odds ratios (OR) with 95% confidence intervals (95% CI) expressed as (1-OR) x100.

Results: Protection from prior infection against SARS-CoV-2 reinfection was 86.3% (95% CI, 81.8 to 89.7) for Lambda, 73.0% (95% CI, 62.9 to 80.3) for Gamma, 84.7% (95% CI, 82.1 to 86.9) for Delta, 34.9% (95% CI, 25.5 to 43.1) for Omicron BA.1, 67.0% (95% CI, 58.7 to 73.6) for Omicron BA.2.12.1, 49.1% (95% CI, 40.5 to 56.5) for Omicron BA.4, 44.8% (95% CI, 39.9 to 49.3) for Omicron BA.5, 29.4% (95% CI, 18.2 to 39.1) for Omicron BQ, and 8.6% (95% CI, -0.5 to 16.9) for Omicron XBB.

Conclusions: Prior infection provides significant protection against SARS-CoV-2 reinfection episodes, although this varies widely among the different Omicron sublineages.

The biomedical publications industry is vital to progress in science and health care. We observe that this industry has become unnecessarily complex and expensive for researchers and readers, impeding the sharing of research findings. In this perspective, we offer selected critiques of this industry and suggest how it might be improved.

Background: Two novel malaria vaccines, RTS,S and R21, mark a significant step forward in malaria research, but eradication demands vaccines with higher efficacy. Recent trials using late-arresting genetically attenuated parasites (LA-GAP) highlight their effectiveness as next-generation vaccines, likely through CD8⁺ T-cell activation targeting late liver-stage parasites. However, the distribution of LA-GAP-activated T cells in different organs that culminate towards high-level protection in the liver remains unclear.

Methods: This study aimed to map immune responses in the livers and lungs of mice immunized with LA-GAP, shedding light on the role of different organs in priming T-cell responses towards immunity.

Results: Particularly in the lungs we found an impressive increase of CD8⁺, double negative T cells (5%), γδ (2.5%), effector memory CD8⁺ T cells (46%), and tissue resident memory CD8⁺ T cells (3%). These lung T cells are highly activated (expressing CD11c, Ki67, KLRG1) and exhibited 4-fold higher Granzyme A expression and significant TNF⁺ cell increases as compared to their liver counterparts (10.2% vs 2.6%). These differences start already at the early 2-day timepoint at which time the lungs show an impressive 10.2% increase in TNF⁺ CD8⁺ T cells, whereas the liver shows a more modest increase of 2.6% of these cells.

Conclusion: These findings highlight the lungs as a crucial site for immune priming and T-cell activation, underscoring the need for further investigation of organ-specific responses to fully understand the potential of LA-GAP immunization as a powerful strategy in the fight against malaria.