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BackgroundWe investigated the safety and immunogenicity of two recombinant COVID-19 DNA vaccine candidates in first-in-human trials. GX-19 contains plasmid DNA encoding SARS-CoV-2 spike protein, and GX-19N contains plasmid DNA encoding SARS-CoV-2 receptor binding domain (RBD) foldon and nucleocapsid protein (NP) as well as plasmid DNA encoding SARS-CoV-2 spike protein. MethodsTwo open-label phase 1 trials of GX-19 and GX-19N safety and immunogenicity were performed in healthy adults aged 19-55 years. GX-19 trial participants received two vaccine injections (1{middle dot}5 mg or 3{middle dot}0 mg, 1:1 ratio) four weeks apart. GX-19N trial participants received two 3{middle dot}0 mg vaccine injections four weeks apart. FindingsBetween June 17 and July 30 and December 28 and 31, 2020, 40 and 21 participants were enrolled in the GX-19 and GX-19N trials, respectively. Thirty-two participants (52{middle dot}5%) reported 80 treatment-emergent adverse events (AE) after vaccination. All solicited AEs were mild except one case of moderate fatigue reported in the 1{middle dot}5 mg GX-19 group. Binding antibody responses increased after vaccination in all groups. The geometric mean titers (GMTs) of spike-binding antibodies on day 57 were 85{middle dot}74, 144{middle dot}20, and 201{middle dot}59 in the 1{middle dot}5 mg, 3{middle dot}0 mg GX-19 groups and the 3{middle dot}0 mg GX-19N group, respectively. In GX-19N group, neutralizing antibody response (50% neutralizing titer using FRNT) significantly increased after vaccination, but GMT of neutralizing antibody on day 57 (37.26) was lower than those from human convalescent serum (288.78). GX-19N induced stronger T cell responses than GX-19. The magnitude of GX-19N-induced T cell responses was comparable to those observed in the convalescent PBMCs. GX-19N induced both SARS-CoV-2 spike- and NP-specific T cell responses, and the amino acid sequences of 15-mer peptides containing NP-specific T cell epitopes identified in GX-19N-vaccinated participants were identical with those of diverse SARS-CoV-2 variants InterpretationGX-19N is safe, tolerated and induces humoral and broad SARS-CoV-2-specific T cell response which may enable cross-reactivity to emerging SARS-CoV-2 variants. FundingThis research was supported by Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (HQ20C0016, Republic of Korea). Research in contextO_ST_ABSEvidence before this studyC_ST_ABSTo overcome the COVID-19 outbreak, the development of safe and effective vaccines is crucial. Despite the successful clinical efficacy of the approved vaccines, concerns exist regarding emerging new SARS-CoV-2 variants that have mutated receptor binding domains in the spike protein. We searched PubMed for research articles published up to May 1, 2021, using various combinations of the terms "COVID-19" or "SARS-CoV-2", "vaccine", and "clinical trial". No language or data restrictions were applied. We also searched the ClinicalTrials.gov registry and World Health Organization (WHO) draft landscape of COVID-19 candidate vaccines for ongoing trials of COVID-19 vaccines up to May 1, 2021. Ten DNA-based vaccines, including the vaccine candidate reported here, are in ongoing clinical trials. Among these, safety and immunogenicity results were reported from only one phase 1 trial of a DNA vaccine against SARS-CoV-2 (INO-4800). INO-4800 demonstrated favorable safety and tolerability and was immunogenic, eliciting humoral and/or cellular immune responses in all vaccinated subjects. There is only one ongoing clinical trial of a vaccine against SARS-CoV-2 variants (mRNA-1273.351). Added value of this studyThis is the first-in-human phase 1 trial in healthy adults of a recombinant DNA vaccine for COVID-19 (GX-19N) containing the coding regions of both the spike and nucleocapsid proteins. This trial showed that GX-19N is safe, tolerated, and able to induce both humoral and cellular responses. A two-dose vaccination of 3{middle dot}0 mg GX-19N (on days 1 and 29) induced significant humoral and cellular responses. The neutralizing geometric mean titers in individuals vaccinated with GX-19N were lower than those of human convalescent sera. However, the GX-19N group showed increased T cell responses, which was similar to those analyzed using convalescent PBMCs. Furthermore, GX-19N induced not only SARS-CoV-2 spike-specific T cell responses but also broad nucleocapsid-specific T cell responses, which were also specific to SARS-CoV-2 variants. Implications of all the available evidenceIt is important to note that GX-19N contains a plasmid encoding both the spike and nucleocapsid proteins, and that it showed broad SARS-CoV-2-specific T cell responses, which may allow cross-reactivity with emerging SARS-CoV-2 variants. Based on these safety and immunogenicity findings, GX-19N was selected for phase 2 immunogenicity trials.
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Background@#The temporal changes in the Staphylococcus aureus genotypes causing S. aureusbacteremia (SAB) and the corresponding clinical changes over the last decade in South Korea are rarely investigated. @*Methods@#A longitudinal study of adult SAB patients was conducted in a large referral hospital in Seoul, South Korea. Adult monomicrobial SAB patients were enrolled between August 2008 and December 2018. Genotyping was performed by multilocus sequence typing (MLST) and staphylococcal protein A (spa) typing. Trends in changes were identified by linear regression analysis. @*Results@#Of 1782 adult SAB patients, the blood isolates of 1,778 (99.8%) and 1,634 (91.7%) were determined to be MLST and spa type, respectively. ST5 (–2.626%/year) and ST239 (–0.354%/year) decreased during the study period (P < 0.001 for both), but ST72 (2.009%/ yr)-and ST8 (0.567%/yr) increased (P < 0.001 for both). The most common genotype was changed from ST5 in 2008 (44.9%) to ST72 in 2018 (36.3%). Panton-Valentine leukocidinpositive spa-t008-MRSA (USA300) was found in 28.6%. Central venous catheter (CVC)-related SAB (–2.440%/yr) and persistent SAB (–1.016%/yr) decreased, but mortality and recurrence rates were unchanged. @*Conclusion@#Over the last decade, the hospital clones ST5 and ST239 have been replaced by community genotype ST72. This was associated with decreased CVC-related and persistent SAB. Increased USA300 was observed in community and hospital settings. Further research is required to identify the reasons for the ST72 epidemic and predict the impending epidemic of ST8 strains, including USA300.
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Background@#The temporal changes in the Staphylococcus aureus genotypes causing S. aureusbacteremia (SAB) and the corresponding clinical changes over the last decade in South Korea are rarely investigated. @*Methods@#A longitudinal study of adult SAB patients was conducted in a large referral hospital in Seoul, South Korea. Adult monomicrobial SAB patients were enrolled between August 2008 and December 2018. Genotyping was performed by multilocus sequence typing (MLST) and staphylococcal protein A (spa) typing. Trends in changes were identified by linear regression analysis. @*Results@#Of 1782 adult SAB patients, the blood isolates of 1,778 (99.8%) and 1,634 (91.7%) were determined to be MLST and spa type, respectively. ST5 (–2.626%/year) and ST239 (–0.354%/year) decreased during the study period (P < 0.001 for both), but ST72 (2.009%/ yr)-and ST8 (0.567%/yr) increased (P < 0.001 for both). The most common genotype was changed from ST5 in 2008 (44.9%) to ST72 in 2018 (36.3%). Panton-Valentine leukocidinpositive spa-t008-MRSA (USA300) was found in 28.6%. Central venous catheter (CVC)-related SAB (–2.440%/yr) and persistent SAB (–1.016%/yr) decreased, but mortality and recurrence rates were unchanged. @*Conclusion@#Over the last decade, the hospital clones ST5 and ST239 have been replaced by community genotype ST72. This was associated with decreased CVC-related and persistent SAB. Increased USA300 was observed in community and hospital settings. Further research is required to identify the reasons for the ST72 epidemic and predict the impending epidemic of ST8 strains, including USA300.
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Through this meta-analysis, we sought to examine the prevalence of, risks for, and factors associated with bullying involvement (victimization, perpetration, perpetration-victimization) among students with autism spectrum disorder (ASD). Additionally, we attempted to examine sources of variance in the prevalence and effect sizes of bullying in students with ASD across studies. Systematic database and literature review identified 34 relevant studies (31 for Western countries, three for Eastern countries). Pooled prevalence estimates for victimization, perpetration, and perpetration-victimization in general were 67%, 29%, and 14%, respectively.The risk of victimization in students with ASD was significantly higher than that in typically developing students and students with other disabilities. Further, deficits in social interaction and communication, externalizing symptoms, internalizing symptoms, and integrated inclusive school settings were related to higher victimization, and externalizing symptoms were related to higher perpetration. Finally, moderation analyses revealed significant variations in the pooled prevalences thereof depending on culture, age, school settings, and methodological quality and in the pooled effect sizes according to publication year and methodological quality. Our results highlight needs for bullying intervention for students with ASD, especially those who are younger, are in an inclusive school setting, and have higher social difficulties and externalizing/internalizing symptoms; for intensive research of bullying experiences among students with ASD in Eastern countries; and for efforts to improve the methodological quality of such research.
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Interleukin-17 (IL-17) is secreted by a class of helper T cells called Th17 cells, which stimulates keratinocytes to secrete proinflammatory mediator and to recruit other inflammatory cells in psoriatic skins. IL-17A inhibitor was approved for the management of psoriatic arthritis by FDA. It is the one of the biologics approved as first-line therapy for the management of psoriasis. But several studies show some side effects of IL-17A inhibitor such as upper respiratory infection and fungal infection like Candida albicans. Herein we report a widespread dermatophytosis during IL-17A inhibitor treatment. A 66-year-old male patient, with tinea unguium and chronic plaque psoriasis for several decades, presented with multiple erythematous scaly macules and patches for 2 weeks. He medicated IL-17A inhibitor for treating psoriasis total 3 times and last injection was 1 week ago. Dermatological examination revealed the involvement of 20% body surface area in the form of erythematous scaly macules and patches. KOH mount revealed the presence of numerous hyphae. The patient was started on oral terbinafine, topical isoconazole and efinaconazole. His skin lesions were improved after 1 month of anti-fungal therapy. IL-17 plays an important role in mucocutaneous microbial defense. So, fungal infection should be checked in using IL-17A inhibitor patients periodically.
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BACKGROUND: The number of immigrants with tuberculosis (TB) increases each year in South Korea. Determining the transmission dynamics based on whole genome sequencing (WGS) to cluster the strains has been challenging. METHODS: WGS, annotation refinement, and orthology assignment for the GenBank accession number acquisition were performed on two clinical isolates from Chinese immigrants. In addition, the genomes of the two isolates were compared with the genomes of Mycobacterium tuberculosis isolates, from two native Korean and five native Chinese individuals using a phylogenetic topology tree based on the Multiple Alignment of Conserved Genomic Sequence with Rearrangements (Mauve) package. RESULTS: The newly assigned accession numbers for two clinical isolates were CP020381.2 (a Korean-Chinese from Yanbian Province) and CP022014.1 (a Chinese from Shandong Province), respectively. Mauve alignment classified all nine TB isolates into a discriminative collinear set with matched regions. The phylogenetic analysis revealed a rooted phylogenetic tree grouping the nine strains into two lineages: (1) strains from Chinese individuals and (2) strains from Korean individuals. CONCLUSION: Phylogenetic trees based on the Mauve alignments were supposed to be useful in revealing the dynamics of TB transmission from immigrants in South Korea, which can provide valuable information for scaling up the TB screening policy for immigrants.
