Live-attenuated pediatric parainfluenza vaccine expressing 6P-stabilized SARS-CoV-2 spike protein is protective against SARS-CoV-2 variants in hamsters

The pediatric live-attenuated bovine/human parainfluenza virus type 3 (B/HPIV3)-vectored vaccine expressing the prefusion-stabilized SARS-CoV-2 spike (S) protein (B/HPIV3/S-2P) was previously evaluated in vitro and in hamsters. To improve its immunogenicity, we generated B/HPIV3/S-6P, expressing S further stabilized with 6 proline mutations (S-6P). Intranasal immunization of hamsters with B/HPIV3/S-6P reproducibly elicited significantly higher serum anti-S IgA/IgG titers than B/HPIV3/S-2P; hamster sera efficiently neutralized variants of concern (VoCs), including Omicron variants. B/HPIV3/S-2P and B/HPIV3/S-6P immunization protected hamsters against weight loss and lung inflammation following SARS-CoV-2 challenge with the vaccine-matched strain WA1/2020 or VoCs B.1.1.7/Alpha or B.1.351/Beta and induced near-sterilizing immunity. Three weeks post-challenge, B/HPIV3/S-2P- and B/HPIV3/S-6P-immunized hamsters exhibited a robust anamnestic serum antibody response with increased neutralizing potency to VoCs, including Omicron sublineages. B/HPIV3/S-6P primed for stronger anamnestic antibody responses after challenge with WA1/2020 than B/HPIV3/S-2P. B/HPIV3/S-6P will be evaluated as an intranasal vaccine to protect infants against both HPIV3 and SARS-CoV-2. AUTHOR SUMMARYSARS-CoV-2 infects and causes disease in all age groups. While injectable SARS-CoV-2 vaccines are effective against severe COVID-19, they do not fully prevent SARS-CoV-2 replication and transmission. This study describes the preclinical comparison in hamsters of B/HPIV3/S-2P and B/HPIV3/S-6P, live-attenuated pediatric vector vaccine candidates expressing the "2P" prefusion stabilized version of the SARS-CoV-2 spike protein, or the further-stabilized "6P" version. B/HPIV3/S-6P induced significantly stronger anti-S serum IgA and IgG responses than B/HPIV3/S-2P. A single intranasal immunization with B/HPIV3/S-6P elicited broad systemic antibody responses in hamsters that efficiently neutralized the vaccine-matched isolate as well as variants of concern, including Omicron. B/HPIV3/S-6P immunization induced near-complete airway protection against the vaccine-matched SARS-CoV-2 isolate as well as two variants. Furthermore, following SARS-CoV-2 challenge, immunized hamsters exhibited strong anamnestic serum antibody responses. Based on these data, B/HPIV3/S-6P will be further evaluated in a phase I study.

Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine candidate is protective in macaques

Pediatric SARS-CoV-2 vaccines are needed that elicit immunity directly in the airways, as well as systemically. Building on pediatric parainfluenza virus vaccines in clinical development, we generated a live-attenuated parainfluenza virus-vectored vaccine candidate expressing SARS-CoV-2 prefusion-stabilized spike (S) protein (B/HPIV3/S-6P) and evaluated its immunogenicity and protective efficacy in rhesus macaques. A single intranasal/intratracheal dose of B/HPIV3/S-6P induced strong S-specific airway mucosal IgA and IgG responses. High levels of S-specific antibodies were also induced in serum, which efficiently neutralized SARS-CoV-2 variants of concern. Furthermore, B/HPIV3/S-6P induced robust systemic and pulmonary S-specific CD4+ and CD8+ T-cell responses, including tissue-resident memory cells in lungs. Following challenge, SARS-CoV-2 replication was undetectable in airways and lung tissues of immunized macaques. B/HPIV3/S-6P will be evaluated clinically as pediatric intranasal SARS-CoV-2/parainfluenza virus type 3 vaccine. One-Sentence SummaryIntranasal parainfluenza virus-vectored COVID-19 vaccine induces anti-S antibodies, T-cell memory and protection in macaques.

Isolation and characterization of fowl adenovirus serotype 4 from chickens with hydropericardium syndrome in Korea / 대한수의학회지

Four strains of fowl adenovirus (FAdV) were isolated from 4 flocks of broiler or layer chickens affected by hydropericardium syndrome in Korea. These FAdVs were classified as serotype 4 by restriction fragment length polymorphism patterns of hexon genes and whole genomes. The virus exhibited cytopathic effects consisting of rounding, ballooning and clustering in primary chicken embryo liver cell cultures. In transmission electron microscopy, virus particles in hexagonal shape aggregated exclusively in the nuclei of hepatocytes of the chickens as the typical appearances in adenovirus infections. Buoyant density of the virus in cesium chloride (CsCl) was 1.34 g/mL. The virus was stable to chloroform, ether, 50~70% ethanol, acidic condition at pH 3, 0.25% trypsin (1 : 250), heat at 50degrees C for 30 min, but labile to 100% ethanol, heat at 52~60degrees C for 30 min, 1 M MgCl2 at 50degrees C for 1 h, 1 : 2,000 formalin (37%). All of the physicochemical properties pertained to the characteristics of adenoviruses. Eight viral polypeptides were determined in CsCl-purified virus by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

A Case of Massive Perirenal Hematoma in a Patient with Hemorrhagic Fever with Renal Syndrome / 대한신장학회잡지

Hemorrhagic fever with renal syndrome is characterized clinically by the triad of fever, hemorrhage and renal failure. The hemorrhage in hemorrhagic fever with renal syndrome(HFRS) varies from transient petechial lesions to fulminant and massive bleeding. The latter can be an important cause of death in HFRS. We here report a case of massive perirenal hematoma in a patient with HFRS. A 17-year-old male was admited to our hospital presenting with fever, sore throat, nausea and oliuria. Computed tomography was performed at the 2nd day of hospitalization due to abruptly developing right flank pain and anemia and showed perirenal hematoma on the right kidney. He was diagnosed as HFRS and treated with hemodialysis, fluid infusion, and transfusion. There was no evidence of further blood loss at the 7th day of hospitalization. After conservative treatment, he recovered from HFRS.

Evaluation of Residual Renal Function of Chronic Renal Failure at the Initiation of Dialysis / 대한신장학회잡지

The decision to initiate dialysis in a patient with progressive renal disease often depends on the physician's assessment of the patient's subjective symptoms of uremia. Decreased residual renal function and malnutrition at the initiation of dialysis is a strong predictor of subsequent increased relative risk of death on dialysis. In this context, to investigate the residual renal function and nutritional parameters of chronic renal failure patients at the initiation of dialysis, 103 patients with chronic renal failure patients were studied. The residual renal function(estimated GFR) was ascertained by measuring simultaneously the 24-h creatinine and urea clearances and averaging the two values and Krt/V. Nutritional parameters were ascertained by measuring the nPNA, %LBM and serum albumin. The mean estimated GFR was 5.97+/-2.88ml/min, the mean weekly Krt/V was 1.24+/-0.80, the mean %LBM was 61.66+/-22.41 and the mean nPNA was 0.89+/-0.30 g/day/kg. We knew that the time of initiation of dialysis, which was based on the manifestation of symptoms of certain patients in conjunction with selected laboratories indices, was delayed than that of NKF- DOQI recommendation. This study suggests that the timely initiation of dialysis is determined by not clinical symptoms and signs but estimated GFR, krt/V and nPNA.

The Effect of Regional Anesthesia for Premedication of Esophagogastroduodenoscopy on Swallowing Motor Function / 대한소화기내시경학회지

Regianal anesthesia applied by means of a gargle provides satisfactory analgesia for premedication of esophagogastroduodenoscopy (EGD). To access the influence of 2% lidocaine hydrochloride after regional anesthesia on oropharyngeal components of swal- lowing, we used the videofluorographic swallowing study for the evaluation of pharyngeal architecture, time of pharyngeal barium passage, and the submental surface EMG(S-EMG) for the evaluation of functional changes in skeletal muscle. Measurements were made in 10 healthy volunteers without any oropharyngeal problems. There was no liquid aspiration symptoms or signs before and after regional anesthesia application. Also, there were no structural changes in pharyngeal swallowing motion and no significant prolongation of pharyngeal barium transit time. But regional anesthesia affected the eletro-activities in swallowing skeletal muscle, i.e, the swallowing durations, peak amplitudes of peristaltic wave, and area under curves in S-EMG, which returned to pre-anesthesia levels in 60 minute's time. Therefore, it will be recommended to avoid meal within 60 minute's after regional anesthesia for EGD.

A Case of Endobronchial Lipoma causing left lung collapse / 대한내과학회지

Endobronchial lipoma is a rare, benign neoplasm of the large bronchi, which makes up about 0.1 percent of all lung tumors. It can produce irreversible parenchymal lung damage or bronchiectasis if diagnosis and treatment are delayed. The treatment of endobronchial lipoma is early removal and surgical procedures depend on the status of distal parenchymal lung damage. We experienced a case of endobronchial lipoma in 53 year-old female patient, which caused total collapse of left lung and save left lung by enucleation of tumor via bronchotomy.

Anterior Mediastinal Mass with Cavitation / 결핵

Radiological criteria such as smooth, sharply defined interface, obtuse angles between lesion and lung and intimate effect on mediastinal contents were usually used to differentiate mediastinal lesion from parenchymal lung lesion Recently, we experienced a 60-year-old female presenting with anterior mediastinal mass with cavitation. Grossly it was proven to be peripheral lung cancer adjacent to mediastinum and microscopically it was squamous cell carcinoma. The gross pathological findings of surgical specimen were very well correlated with radiological findings. The unique location such as lung periphery and attachment to mediastinum led us to misdiagnosis of anterior mediastinal mass such as germ-cell tumor and neurogenic tumor.