• Korean Journal of Community Nutrition
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• v.28 no.1
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• pp.61-73
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• 2023

Objectives: Prophylactic vaccines against high-risk human papillomaviruses (HR-HPVs) hold promise to prevent the development of higher grade cervical intraepithelial neoplasia (CIN 2+) and cervical cancer (CC) that develop due to HR-HPV genotypes that are included in HPV vaccines, but women will continue to develop CIN 2+ and CC due to HR-HPV genotypes that are not included in the quadrivalent HPV vaccine (qHPV) and 9-valent HPV vaccine (9VHPV). Thus, the current vaccines are likely to decrease but not entirely prevent the development of CIN 2+ or CC. The purpose of the study was to determine the prevalence and determinants of CIN 2+ that develop due to HR-HPVs not included in vaccines. Methods: Study population consisted of 1476 women tested for 37 HPVs and known to be negative for qHPVs (6/11/16/18, group A, n = 811) or 9VHPVs (6/11/16/18/31/33/45/52/58, group B, n = 331), but positive for other HR-HPVs. Regression models were used to determine the association between plasma concentrations of micronutrients, socio-demographic, lifestyle factors and risk of CIN 2+ due to HR-HPVs that are not included in vaccines. Results: The prevalence of infections with HPV 31, 33, 35 and 58 that contributed to CIN 2+ differed by race. In group A, African American (AA) women and current smokers were more likely to have CIN 2 (OR = 1.76, P = 0.032 and 1.79, P = 0.016, respectively) while in both groups of A and B, those with higher vitamin B12 were less likely to have similar lesions (OR = 0.62, P = 0.036 and 0.45, P = 0.035, respectively). Conclusions: We identified vitamin B12 status and smoking as independent modifiable factors and ethnicity as a factor that needs attention to reduce the risk of developing CIN 2+ in the post vaccination era. Continuation of tailored screening programs combined with non-vaccine-based approaches are needed to manage the residual risk of developing HPV-related CIN 2+ and CC in vaccinated women.

• IMMUNE NETWORK
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• v.22 no.5
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• pp.41.1-41.16
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• 2022

The human antimicrobial peptide LL-37 has chemotactic and modulatory activities in various immune cells, including dendritic cells. Because of its characteristics, LL-37 can be considered an adjuvant for vaccine development. In this study, we confirmed the possible adjuvant activity of LL-37 in mucosal vaccine development against Middle East respiratory syndrome-coronavirus (MERS-CoV) by means of intranasal immunization in C57BL/6 and human dipeptidyl peptidase 4 (hDPP4)-transgenic (hDPP4-Tg) mice. Intranasal immunization using the receptor-binding domain (RBD) of MERS-CoV spike protein (S-RBD) recombined with LL-37 (S-RBD-LL-37) induced an efficient mucosal IgA and systemic IgG response with virus-neutralizing activity, compared with S-RBD. Ag-specific CTL stimulation was also efficiently induced in the lungs of mice that had been intranasally immunized with S-RBD-LL-37, compared with S-RBD. Importantly, intranasal immunization of hDPP4-Tg mice with S-RBD-LL-37 led to reduced immune cell infiltration into the lungs after infection with MERS-CoV. Finally, intranasal immunization of hDPP4-Tg mice with S-RBD-LL-37 led to enhanced protective efficacy, with increased survival and reduced body weight loss after challenge infection with MERS-CoV. Collectively, these results suggest that S-RBD-LL-37 is an effective intranasal vaccine candidate molecule against MERS-CoV infection.

• Clinical and Experimental Vaccine Research
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• v.13 no.1
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• pp.42-53
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• 2024

Purpose: Conduct a systematic review of case reports and case series regarding the development of acute abdomen following coronavirus disease 2019 (COVID-19) vaccination, to describe the possible association and the clinical and demographic characteristics in detail. Materials and Methods: This study included case report studies and case series that focused on the development of acute abdomen following COVID-19 vaccination. Systematic review studies, literature, letters to the editor, brief comments, and so forth were excluded. PubMed, Scopus, EMBASE, and Web of Science databases were searched until June 15, 2023. The Joanna Briggs Institute tool was used to assess the risk of bias and the quality of the study. Descriptive data were presented as frequency, median, mean, and standard deviation. Results: Seventeen clinical case studies were identified, evaluating 17 patients with acute abdomen associated with COVID-19 vaccination, which included acute appendicitis (n=3), acute pancreatitis (n=9), diverticulitis (n=1), cholecystitis (n=2), and colitis (n=2). The COVID-19 vaccine most commonly linked to acute abdomen was Pfizer-BioNTech (messenger RNA), accounting for 64.71% of cases. Acute abdomen predominantly occurred after the first vaccine dose (52.94%). All patients responded objectively to medical (88.34%) and surgical (11.76%) treatment and were discharged within a few weeks. No cases of death were reported. Conclusion: Acute abdomen is a rare complication of great interest in the medical and surgical practice of COVID-19 vaccination. Our study is based on a small sample of patients; therefore, it is recommended to conduct future observational studies to fully elucidate the underlying mechanisms of this association.

• The Korean Society of Law and Medicine
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• v.21 no.3
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• pp.37-75
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• 2020

There have been affluent studies on the development of new drugs and these efforts have been crystallized into a separate field of pharmacology. Yet, a normative analysis pertinent to the development of new medicine is still in a dire need, except for studies regarding medical ethics. This piece of work aims to contemplate on the legal issues concerning the development of new drug, encompassing each and every stage of the development. In order to maximize the practicability of the research method adopted as aforementioned, this work strives to analyze the developing process of COVID-19 vaccine. The first step would be to introduce the developmental stages of inventing a new drug, especially that of a COVID-19 vaccine. After then, legal issues related to each developmental stage would be discussed. Henceforth, the legal analysis would contribute to predicting upcoming legal complexities and will be able to offer normative implications for the invention of new medicines.

• Parasites, Hosts and Diseases
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• v.55 no.1
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• pp.15-20
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• 2017

The aim of this study was to identify antigens for a vaccine or drug target to control rabbit coccidiosis. A combination of 2-dimensional electrophoresis, immunoblotting, and mass spectrometric analysis were used to identify novel antigens from the sporozoites of Eimeria stiedae. Protein spots were recognized by the sera of New Zealand rabbits infected artificially with E. stiedae. The proteins were characterized by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF/TOF-MS) analysis in combination with bioinformatics. Approximately 868 protein spots were detected by silver-staining, and a total of 41 immunoreactive protein spots were recognized by anti-E. stiedae sera. Finally, 23 protein spots were successfully identified. The proteins such as heat shock protein 70 and aspartyl protease may have potential as immunodiagnostic or vaccine antigens. The immunoreactive proteins were found to possess a wide range of biological functions. This study is the first to report the proteins recognized by sera of infected rabbits with E. stiedae, which might be helpful in identifying potential targets for vaccine development to control rabbit coccidiosis.

• Korean Journal of Veterinary Research
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• v.51 no.3
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• pp.193-201
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• 2011

An attenuated vaccine strain AVR1/08 of Korean respiratory type of infectious bronchitis virus (IBV) was developed by 89th passages of IBV D85/06 strain in chicken eggs. The AVR1/08 strain had higher virus titer at least 20 times ($10^{1.3}$) than the parent virus D85/06 by egg inoculation method. The AVR1/08 strain had a single point mutation (S to Y) at position 56 of spike protein of IBV compared to parent virus IBV D85/06 strain. The mutation was observed consistently at viruses after 47th passage in chicken eggs. The AVR1/08 strain showed no virulence even after 6 passages in chickens and all chickens inoculated induced anti-IBV antibody 14 days after vaccination. The AVR1/08 strain had broad protective efficacy against QX type Korean nephropathogenic virus (Q43/06 strain), KM91 type Korean nephropathogenic virus (KM91 strain) and Korean respiratory virus (D85/06 strain). In contrast, Massachusetts (Mass) type attenuated vaccine strain H120 showed protection of 37.5 to 50% against these three viruses. Our results indicate that the AVR1/08 strain has potential as an attenuated vaccine effective in controlling IBVs circulating in Korea.

• Parasites, Hosts and Diseases
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• v.53 no.4
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• pp.385-394
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• 2015

Leishmaniasis is a worldwide uncontrolled parasitic disease due to the lack of effective drug and vaccine. To speed up effective drug development, we need powerful methods to rapidly assess drug effectiveness against the intracellular form of Leishmania in high throughput assays. Reporter gene technology has proven to be an excellent tool for drug screening in vitro. The effects of reporter proteins on parasite infectivity should be identified both in vitro and in vivo. In this research, we initially compared the infectivity rate of recombinant Leishmania major expressing stably enhanced green fluorescent protein (EGFP) alone or EGFP-luciferase (EGFP-LUC) with the wild-type strain. Next, we evaluated the sensitivity of these parasites to amphotericin B (AmB) as a standard drug in 2 parasitic phases, promastigote and amastigote. This comparison was made by MTT and nitric oxide (NO) assay and by quantifying the specific signals derived from reporter genes like EGFP intensity and luciferase activity. To study the amastigote form, both B10R and THP-1 macrophage cell lines were infected in the stationary phase and were exposed to AmB at different time points. Our results clearly revealed that the 3 parasite lines had similar in vitro infectivity rates with comparable parasite-induced levels of NO following interferon-${\gamma}$/lipopolysaccharide induction. Based on our results we proposed the more reporter gene, the faster and more sensitive evaluation of the drug efficiency.

• Microbiology and Biotechnology Letters
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• v.20 no.3
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• pp.301-310
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• 1992

This work was performed to investigate the possibility of using J96 hemolysin(Hly, Hly A) vaccine against urinary tract infecting Escherichia coli. Based on the known sequence of J96 hemolysin which was originally isolated from a pyelonephritis patient, ten 20-mer oligonucleotide probes were synthesized. Radioactive labelled 8 probes showed positive colony blots against most of the hemolysin producing wild type E. coli, while HA484 and HA661 showed 28.3, 71.7% positive blots, respectively. This result means that hemolysin genes are highly conserved. Also, 12 anti-Hly MABs(monoclonal antibodies) showed more than 90% positive immunoblots against secreted hemolysin from wild type E. coli. Especially, the result that MAB132 neutralized hemolysin from all of the wild type E. coli augments the idea that hemolysin will be effective as a vaccine.

• Journal of Veterinary Science
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• v.22 no.6
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• pp.76.1-76.15
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• 2021

Background: The development of a vaccine for Jembrana disease is needed to prevent losses in Indonesia's Bali cattle industry. A DNA vaccine model (pEGFP-C1-tat) that requires a functional delivery system will be developed. Polylactic-co-glycolic acid (PLGA) may have potential as a delivery system for the vaccine model. Objectives: This study aims to evaluate the in vitro potential of PLGA as a delivery system for pEGFP-C1-tat. Methods: Consensus and codon optimization for the tat gene was completed using a bioinformatic method, and the product was inserted into a pEGFP-C1 vector. Cloning of the pEGFP-C1-tat was successfully performed, and polymerase chain reaction (PCR) and restriction analysis confirmed DNA isolation. PLGA-pEGFP-C1-tat solutions were prepared for encapsulated formulation testing, physicochemical characterization, stability testing with DNase I, and cytotoxicity testing. The PLGA-pEGFP-C1-tat solutions were transfected in HeLa cells, and gene expression was observed by fluorescent microscopy and real-time PCR. Results: The successful acquisition of transformant bacteria was confirmed by PCR. The PLGA:DNA:polyvinyl alcohol ratio formulation with optimal encapsulation was 4%:0.5%:2%, physicochemical characterization of PLGA revealed a polydispersity index value of 0.246, a particle size of 925 nm, and a zeta potential value of -2.31 mV. PLGA succeeded in protecting pEGFP-C1-tat from enzymatic degradation, and the percentage viability from the cytotoxicity test of PLGA-pEGFP-C1-tat was 98.03%. The PLGA-pEGFP-C1-tat demonstrated luminescence of the EGFP-tat fusion protein and mRNA transcription was detected. Conclusions: PLGA has good potential as a delivery system for pEGFP-C1-tat.

• Clinical and Experimental Vaccine Research
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• v.12 no.4
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• pp.328-336
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• 2023

Purpose: Human peripheral blood mononuclear cell (PBMC)-based in vitro systems can be of great value in the development and assessment of vaccines but require the right medium for optimal performance of the different cell types present. Here, we compare three commonly used media for their capacity to support innate and adaptive immune responses evoked in PBMCs by Toll-like receptor (TLR) ligands and whole inactivated virus (WIV) influenza vaccine. Materials and Methods: Human PBMCs were cultured for different periods of time in Roswell Park Memorial Institute (RPMI), Dulbecco's minimal essential medium (DMEM), or Iscove's modified DMEM (IMDM) supplemented with 10% fetal calf serum. The viability of the cells was monitored and their responses to TLR ligands and WIV were assessed. Results: With increasing days of incubation, the viability of PBMCs cultured in RPMI or IMDM was slightly higher than that of cells cultured in DMEM. Upon exposure of the PBMCs to TLR ligands and WIV, RPMI was superior to the other two media in terms of supporting the expression of genes related to innate immunity, such as the TLR adaptor protein gene MyD88 (myeloid differentiation factor 88), the interferon (IFN)-stimulated genes MxA (myxovirus resistance protein 1) and ISG56 (interferon-stimulated gene 56), and the leukocyte recruitment chemokine gene MCP1 (monocyte chemoattractant protein-1). RPMI also performed best with regard to the activation of antigen-presenting cells. As for adaptive immunity, when stimulated with WIV, PBMCs cultured in RPMI or IMDM contained higher numbers of IFNγ-producing T cells and secreted more immunoglobulin G than PBMCs cultured in DMEM. Conclusion: Taken together, among the different media assessed, RPMI was identified as the optimal medium for a human PBMC-based in vitro vaccine evaluation system.