Subunit vaccines with a saponin-based adjuvant boost humoral and cellular immunity to MERS coronavirus.

Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks have constituted a public health issue with drastic mortality higher than 34%, necessitating the development of an effective vaccine. During MERS-CoV infection, the trimeric spike protein on the viral envelope is primarily responsible for attachment to host cellular receptor, dipeptidyl peptidase 4 (DPP4). With the goal of generating a protein-based prophylactic, we designed a subunit vaccine comprising the recombinant S1 protein with a trimerization motif (S1-Fd) and examined its immunogenicity and protective immune responses in combination with various adjuvants. We found that sera from immunized wild-type and human DPP4 transgenic mice contained S1-specific antibodies that can neutralize MERS-CoV infection in susceptible cells. Vaccination with S1-Fd protein in combination with a saponin-based QS-21 adjuvant provided long-term humoral as well as cellular immunity in mice. Our findings highlight the significance of the trimeric S1 protein in the development of MERS-CoV vaccines and offer a suitable adjuvant, QS-21, to induce robust and prolonged memory T cell response.

Impact of COVID-19 pandemic in 2020 on the diagnosis and management of breast cancer in Korea: A multi-institutional study

Background: Since the COVID-19 pandemic began in early 2020, there have been many reports that it has had a significant impact on screening, case identification and referral in cancer diagnosis. We investigated the diagnostic and therapeutic status of breast malignancy before and after the COVID-19 pandemic at the multi-institution level. Methods: We have reviewed the records of patients with breast cancer from February 2019 to July 2020 in six university hospitals in Korea. The patients were divided into two groups according to the initial date of cancer diagnosis: Period A, from February to April and Period B, from May to July in 2020. The two groups were compared for the same periods in 2019. The goals were to determine whether breast cancer screening and diagnosis have been delayed and thus resulted in stage migration. We also examined the difference in the number of surgeries in patients diagnosed with breast cancer during those periods. Results: The total of 1,669 breast malignancy diagnosis was made in the grouped periods of 2019, and 1,369 diagnoses in 2020. All patients were screened by PCR test for COVID-19 prior to hospitalization, and none of them tested positive. Overall, there was a 9.9% reduction in the number of diagnoses than in 2019 and the decrease was more significant in Period A (11.1% vs. 8.7%). According to the age, there was no difference until the 30s but decreased from those in their 40s and above. The decline was more pronounced in the elderly. The COVID-19 pandemic has affected breast cancer screening (decreased by 27.4%) and more diminished in Period A (41.0% vs. 19.0%). Invasive breast cancer stage was not statistically different in Period A compare with 2019 (p = 0.170). But the stage in Period B was different (p = 0.032), and more patients were observed in advanced stages in 2020. The decrease in surgery was noticeably observed in Period A (4.6%, from 480 to 438 surgeries) and not in Period B. The analysis of reconstruction surgery was similar. Conclusions: Patients with COVID-19 increased exponentially from late February in Korea. However, the number of patients per day decreased to less than 100 on March 15 and then flattened. The health care system for cancer was not overloaded and restrictions on visiting hospital were minimal. Analysis in the pandemic period of the 6-month showed that the number of breast cancer screening, diagnosis and surgeries decreased compared with the previous year. Those decreases were prominent in Period A when the COVID-19 patient surged. The upstage migration of breast cancer was generally insignificant but slightly occurred in Period B. The outbreak of infectious disease makes patients reluctant to come to the hospital, especially in the elderly. We need to discuss the potential long-lasting deleterious effect of the COVID-19 pandemic on cancer diagnosis and management. And we should prepare for how to deal with the backlog caused by the COVID-19 pandemic.

Consideration of Convolutional Neural Networks for Image Processing of Capillaries

The Convolutional Neural Network (CNN) is an effective algorithm in deep learning and the performance which the CNN brings in life problem is recognized worthily. Tobacco is one of the biggest public health threats and results in 8 million deaths every year through cardiovascular diseases, lung disorders, cancers, diabetes, and hypertension. There are several methods used in hospitals for inspecting their own health, however, they are difficult to use in daily life because all inspecting devices are large-scale and complex. Thus, the purpose of this study was to propose a new method to self-check the effect of smoking on capillaries and surface skin in daily life, then evaluate the usefulness of the proposed method. The dataset was collected from the 26 human subjects through the capillaroscopy;13 subjects were the smoker and the 13 were the non-smoker. Through all of the results for the recognition of the difference between smokers and non-smokers, it was confirmed that conventional methods to extract featured points from the edge or corner points such as ssim (structural similarity) and sift (scale-invariant feature transform) was not so good for the image processing of capillaries. However, it was found that CNN worked well with over 80% accuracy. It was discussed that efficientnet with the compound scaling was so good for the small dataset with the comparison of resnet50, vgg16, densenet121 with one scaling factor, although COVID-19 virus affected the dataset making procedure measured from human subjects directly.

Middle East Respiratory Syndrome Coronavirus Nucleocapsid Protein Suppresses Type I and Type III Interferon Induction by Targeting RIG-I Signaling.

Type I and type III interferons (IFNs) are the frontline of antiviral defense mechanisms that trigger hundreds of downstream antiviral genes. In this study, we observed that MERS-CoV nucleocapsid (N) protein suppresses type I and type III IFN gene expression. The N protein suppresses Sendai virus-induced IFN-ß and IFN-λ1 by reducing their promoter activity and mRNA levels, as well as downstream IFN-stimulated genes (ISGs). Retinoic acid-inducible gene I (RIG-I) is known to recognize viral RNA and induce IFN expression through tripartite motif-containing protein 25 (TRIM25)-mediated ubiquitination of RIG-I caspase activation and recruitment domains (CARDs). We discovered that MERS-CoV N protein suppresses RIG-I-CARD-induced, but not MDA5-CARD-induced, IFN-ß and IFN-λ1 promoter activity. By interacting with TRIM25, N protein impedes RIG-I ubiquitination and activation and inhibits the phosphorylation of transcription factors IFN-regulatory factor 3 (IRF3) and NF-κB that are known to be important for IFN gene activation. By employing a recombinant Sindbis virus-EGFP replication system, we showed that viral N protein downregulated the production of not only IFN mRNA but also bioactive IFN proteins. Taken together, MERS-CoV N protein functions as an IFN antagonist. It suppresses RIG-I-induced type I and type III IFN production by interfering with TRIM25-mediated RIG-I ubiquitination. Our study sheds light on the pathogenic mechanism of how MERS-CoV causes disease.IMPORTANCE MERS-CoV causes death of about 35% of patients. Published studies showed that some coronaviruses are capable of suppressing interferon (IFN) expression in the early phase of infection and MERS-CoV proteins can modulate host immune response. In this study, we demonstrated that MERS-CoV nucleocapsid (N) protein suppresses the production of both type I and type III IFNs via sequestering TRIM25, an E3 ubiquitin ligase that is essential for activating the RIG-I signaling pathway. Ectopic expression of TRIM25 rescues the suppressive effect of the N protein. In addition, the C-terminal domain of the viral N protein plays a pivotal role in the suppression of IFN-ß promoter activity. Our findings reveal how MERS-CoV evades innate immunity and provide insights into the interplay between host immune response and viral pathogenicity.