Dabie Bandavirus (DBV), previously known as Severe Fever with Thrombocytopenia Syndrome (SFTS) Virus, induces a characteristic thrombocytopenia with a mortality rate ranging from 12% to as high as 30%. The sero-prevalence of DBV in healthy people is not significantly different among age groups, but clinically diagnosed SFTS patients are older than ~50 years, suggesting that age is the critical risk factor for SFTS morbidity and mortality. Accordingly, our immune-competent ferret model demonstrates an age (>4 years old)-dependent DBV infection and pathogenesis that fully recapitulates human clinical manifestation. To protect the aged population from DBV-induced SFTS, vaccine should carry robust immunogenicity with high safety profile. Previous studies have shown that glycoproteins Gn/Gc are the most effective antigens to induce both neutralizing antibody (NAb)- and T cell-mediated immunity for full protection from DBV infection. Here, we report the development of a protein subunit vaccine with 24-mer self-assembling ferritin (FT) nanoparticle to present the DBV Gn head region (GnH) to enhance immunogenicity. Anion exchange chromatography and size exclusion chromatography readily purified the GnH-FT nanoparticles to homogeneity with structural integrity. Mice immunized with GnH-FT nanoparticles induced robust NAb response and T-cell immunity against DBV Gn. Furthermore, aged ferrets immunized with GnH-FT nanoparticles were fully protected from DBV challenge without SFTS symptoms such as body weight loss, thrombocytopenia, leukopenia, and fatality. This study demonstrates that DBV GnH-FT nanoparticles provide an efficient vaccine efficacy in mouse and aged ferret models and should be an outstanding vaccine candidate targeted for the aged population against fatal DBV infection.

There have been few studies that comprehensively evaluated factors affecting immune responses and the correlation between humoral and cellular immune responses after vector, mix-and-match, and mRNA vaccines against SARS-CoV-2. Therefore, we analyzed the effects of age, sex, and the different vaccine regimens on the immune responses to vaccination against SARS-CoV-2.

Background This study aimed to describe the maternal, obstetrical, and neonatal outcomes in pregnant women with coronavirus disease 2019 (COVID-19) and identify the predictors associated with the severity of COVID-19. Methods This multicenter observational study included consecutive pregnant women admitted because of COVID-19 confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR) test at 15 hospitals in the Republic of Korea between January 2020 and December 2021. Results A total of 257 women with COVID-19 and 62 newborns were included in this study. Most of the patients developed this disease during the third trimester. Nine patients (7.4%) developed pregnancy-related complications. All pregnant women received inpatient treatment, of whom 9 (3.5%) required intensive care, but none of them died. The gestational age at COVID-19 diagnosis (odds ratio [OR], 1.096, 95% confidence interval [CI], 1.04–1.15) and parity (OR, 1.703, 95% CI, 1.13–2.57) were identified as significant risk factors of severe diseases. Among women who delivered, 78.5% underwent cesarean section. Preterm birth (38.5%), premature rupture of membranes (7.7%), and miscarriage (4.6%) occurred, but there was no stillbirth or neonatal death. The RT-PCR test of newborns’ amniotic fluid and umbilical cord blood samples was negative for severe acute respiratory syndrome coronavirus 2. Conclusion At the time of COVID-19 diagnosis, gestational age and parity of pregnant women were the risk factors of disease severity. Vertical transmission of COVID-19 was not observed, and maternal severity did not significantly affect the neonatal prognosis.

This study compared the clinical outcomes and safety of meropenem–colistin versus meropenem–tigecycline in the treatment of adult patients with carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia. A retrospective observational study of patients with CRAB pneumonia was performed at a 1048-bed university-affiliated hospital in the Republic of Korea between June 2013 and January 2020. All adult patients initially treated with meropenem–colistin were compared with those treated with meropenem–tigecycline to evaluate in-hospital mortality and adverse events. Altogether, 66 patients prescribed meropenem–colistin and 24 patients prescribed meropenem–tigecycline were included. All patients had nosocomial pneumonia, and 31.1% had ventilator-associated pneumonia. The minimum inhibitory concentrations of meropenem ≤ 8 μg/mL and tigecycline ≤ 2 μg/mL were 20.0% and 81.1%, respectively. The in-hospital and 28-day mortality rates were 40% and 32%, respectively. In the Cox proportional hazard regression analysis, predictors associated with in-hospital mortality included procalcitonin ≥ 1 ng/mL (adjusted hazard ratio (aHR), 3.39; 95% confidence interval (CI) 1.40–8.19; p = 0.007) and meropenem–colistin combination therapy (aHR, 2.58; 95% CI, 1.07–6.23; p = 0.036). Episodes of nephrotoxicity were significantly more common in the meropenem–colistin group than in the meropenem–tigecycline group (51.5% vs. 12.5%, p = 0.001). Meropenem–tigecycline combination therapy might be a valuable treatment option for patients with CRAB pneumonia.

Background This study aimed to develop and validate a clinical prediction rule to screen older patients at risk of being toxigenic Clostridioides difficile carriers at the time of hospital admission. Methods This retrospective case-control study was performed at a university-affiliated hospital. Active surveillance using a real-time polymerase chain reaction (PCR) assay for the toxin genes of C. difficile was conducted among older patients (≥ 65 years) upon admission to the Division of Infectious Diseases of our institution. This rule was drawn from a derivative cohort between October 2019 and April 2021 using a multivariable logistic regression model. Clinical predictability was evaluated in the validation cohort between May 2021 and October 2021. Results Of 628 PCR screenings for toxigenic C. difficile carriage, 101 (16.1%) yielded positive findings. To establish clinical prediction rules in the derivation cohort, the formula was derived using significant predictors for toxigenic C. difficile carriage at admission, such as septic shock, connective tissue diseases, anemia, recent use of antibiotics, and recent use of proton-pump inhibitors. In the validation cohort, the sensitivity, specificity, and positive and negative predictive values of the prediction rule, based on a cut-off value of ≥ 0.45, were 78.3%, 70.8%, 29.5%, and 95.4%, respectively. Conclusion This clinical prediction rule for identifying toxigenic C. difficile carriage at admission may facilitate the selective screening of high-risk groups. To implement it in a clinical setting, more patients from other medical institutions need to be prospectively examined.

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Purpose: Regulatory T cells (Tregs) exert immunosuppressive functions and hamper anti-tumor immune responses in the tumor microenvironment. Understanding the heterogeneity of intratumoral Tregs, and how it changes with tumor progression, will provide clues regarding novel target molecules of Treg-directed therapies. Experimental Design: From 42 patients with renal cell carcinoma and 5 patients with ovarian cancer, immune cells from tumor and peripheral blood were isolated. We performed multicolor flow cytometry and RNA-sequencing to characterize the phenotypes and heterogeneity of intratumoral Tregs. In vitro functional assays were performed to evaluate suppressive capacity of Tregs and effect of CEACAM1-mediated depletion. The CT26 tumor model was used to evaluate the association between intratumoral Tregs and tumor growth, and examine the in vivo role of CEACAM1+ intratumoral Tregs on anti-tumor immunity. Results: We found that carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) was selectively expressed on intratumoral Tregs, while its expression on peripheral Tregs or other immune cells was low. The CEACAM1+ intratumoral Tregs accumulated with tumor progression, while the CEACAM1– subset did not. Notably, we found that CEACAM1 marked intratumoral Tregs that exhibited highly suppressive and activated phenotypes with substantial clonal expansion. Depletion of CEACAM1-expressing cells from tumor-infiltrating leukocytes led to increased effector functions of tumor-infiltrating T cells. Moreover, CEACAM1+ cell depletion further enhanced anti-PD-1­–mediated reinvigoration of exhausted CD8+ T cells. Conclusions: CEACAM1 marks highly suppressive subset of intratumoral Tregs, and can be a target for selective depletion of intratumoral Tregs. These results may inform future studies on CEACAM1-mediated depletion in cancer patients.

<p>Supplementary Tables S1-7</p>