Comparative Biodistribution Study of Baculoviral and Adenoviral Vector Vaccines against SARS-CoV-2.

Various types of vaccines have been developed against COVID-19, including vector vaccines. Among the COVID-19 vaccines, AstraZeneca's chimpanzee adenoviral vaccine was the first to be commercialized. For viral vector vaccines, biodistribution studies are critical to vaccine safety, gene delivery, and efficacy. This study compared the biodistribution of the baculoviral vector vaccine (AcHERV-COVID19) and the adenoviral vector vaccine (Ad-COVID19). Both vaccines were administered intramuscularly to mice, and the distribution of the SARS-CoV-2 S gene in each tissue was evaluated for up to 30 days. After vaccination, serum and various tissue samples were collected from the mice at each time point, and IgG levels and DNA copy numbers were measured using an enzyme-linked immunosorbent assay and a quantitative real-time polymerase chain reaction. AcHERV-COVID19 and Ad-COVID19 distribution showed that the SARS-CoV-2 spike gene remained predominantly at the injection site in the mouse muscle. In kidney, liver, and spleen tissues, the AcHERV-COVID19 group showed about 2-4 times higher persistence of the SARS-CoV-2 spike gene than the Ad-COVID19 group. The distribution patterns of AcHERV-COVID19 and Ad-COVID19 within various organs highlight their contrasting biodistribution profiles, with AcHERV-COVID19 exhibiting a broader and prolonged presence in the body compared to Ad-COVID19. Understanding the biodistribution profile of AcHERV-COVID19 and Ad-COVID19 could help select viral vectors for future vaccine development.

The N-terminal peptide of the main protease of SARS-CoV-2, targeting dimer interface, inhibits its proteolytic activity.

The main protease (Mpro) of SARS-CoV-2 cleaves 11 sites of iral polypeptide chains and generates essential non-structural proteins for viral replication. Mpro is an important drug target against COVID-19. In this study, we developed a real-time fluorometric turn-on assay system to evaluate Mpro proteolytic activity for a substrate peptide between NSP4 and NSP5. It produced reproducible and reliable results suitable for HTS inhibitor assays. Thus far, most inhibitors against Mpro target the active site for substrate binding. Mpro exists as a dimer, which is essential for its activity. We investigated the potential of the Mpro dimer interface to act as a drug target. The dimer interface is formed of domain II and domain III of each protomer, in which N-terminal ten amino acids of the domain I are bound in the middle as a sandwich. The N-terminal part provides approximately 39% of the dimer interface between two protomers. In the real-time fluorometric turn-on assay system, peptides of the N-terminal ten amino acids, N10, can inhibit the Mpro activity. The dimer interface could be a prospective drug target against Mpro. The N-terminal sequence can help develop a potential inhibitor. [BMB Reports 2023; 56(11): 606-611].

Alterations and Co-Occurrence of C-MYC, N-MYC, and L-MYC Expression are Related to Clinical Outcomes in Various Cancers.

Background and Objectives: MYC, also known as an oncogenic reprogramming factor, is a multifunctional transcription factor that maintains induced pluripotent stem cells (iPSCs). Although MYC is frequently upregulated in various cancers and is correlated with a poor prognosis, MYC is downregulated and correlated with a good prognosis in lung adenocarcinoma. MYC and two other MYC family genes, MYCN and MYCL, have similar structures and could contribute to tumorigenic conversion both in vitro and in vivo. Methods and Results: We systematically investigated whether MYC family genes act as prognostic factors in various human cancers. We first evaluated alterations in the expression of MYC family genes in various cancers using the Oncomine and The Cancer Genome Atlas (TCGA) database and their mutation and copy number alterations using the TCGA database with cBioPortal. Then, we investigated the association between the expression of MYC family genes and the prognosis of cancer patients using various prognosis databases. Multivariate analysis also confirmed that co-expression of MYC/MYCL/MYCN was significantly associated with the prognosis of lung, gastric, liver, and breast cancers. Conclusions: Taken together, our results demonstrate that the MYC family can function not only as an oncogene but also as a tumor suppressor gene in various cancers, which could be used to develop a novel approach to cancer treatment.

Bioactive peptides for boosting stem cell culture platform: Methods and applications.

Peptides, short protein fragments, can emulate the functions of their full-length native counterparts. Peptides are considered potent recombinant protein alternatives due to their specificity, high stability, low production cost, and ability to be easily tailored and immobilized. Stem cell proliferation and differentiation processes are orchestrated by an intricate interaction between numerous growth factors and proteins and their target receptors and ligands. Various growth factors, functional proteins, and cellular matrix-derived peptides efficiently enhance stem cell adhesion, proliferation, and directed differentiation. For that, peptides can be immobilized on a culture plate or conjugated to scaffolds, such as hydrogels or synthetic matrices. In this review, we assess the applications of a variety of peptides in stem cell adhesion, culture, organoid assembly, proliferation, and differentiation, describing the shortcomings of recombinant proteins and their full-length counterparts. Furthermore, we discuss the challenges of peptide applications in stem cell culture and materials design, as well as provide a brief outlook on future directions to advance peptide applications in boosting stem cell quality and scalability for clinical applications in tissue regeneration.

Optimized parameters for effective SARS-CoV-2 inactivation using UVC-LED at 275 nm.

The spread of SARS-CoV-2 infections and the severity of the coronavirus disease of 2019 (COVID-19) pandemic have resulted in the rapid development of medications, vaccines, and countermeasures to reduce viral transmission. Although new treatment strategies for preventing SARS-CoV-2 infection are available, viral mutations remain a serious threat to the healthcare community. Hence, medical devices equipped with virus-eradication features are needed to prevent viral transmission. UV-LEDs are gaining popularity in the medical field, utilizing the most germicidal UVC spectrum, which acts through photoproduct formation. Herein, we developed a portable and rechargeable medical device that can disinfect SARS-CoV-2 in less than 10 s by 99.9%, lasting 6 h. Using this device, we investigated the antiviral effect of UVC-LED (275 nm) against SARS-CoV-2 as a function of irradiation distance and exposure time. Irradiation distance of 10-20 cm, < 10 s exposure time, and UV doses of > 10 mJ/cm2 were determined optimal for SARS-CoV-2 elimination (≥ 99.99% viral reduction). The UVC-LED systems have advantages such as fast-stabilizing intensity and insensitivity to temperature, and may contribute to developing medical devices capable of containing SARS-CoV-2 infection. By demonstrating SARS-CoV-2 inactivation with very short-term UVC-LED irradiation, our study may suggest guidelines for securing a safer medical environment.

Comparison of Six Serological Immunoassays for the Detection of SARS-CoV-2 Neutralizing Antibody Levels in the Vaccinated Population.

Neutralizing antibody (NAb) detection is critical for evaluating herd immunity and monitoring the efficacy of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, quantitative SARS-CoV-2 antibody levels after vaccination were measured by chemiluminescent immunoassays, enzyme immunoassays, and surrogate virus neutralization tests (sVNTs), as well as plaque reduction neutralization tests (PRNT). Sequential blood samples were collected before and 1 and 3 months after vaccination in 30 healthy participants (two doses of Oxford-AstraZeneca [AZ] or Pfizer-BioNTech [BNT]). After vaccination, all sera tested positive for PRNT, with NAb titers ranging from 1:10 to 1:723. Median NAb titers were higher in the BNT vaccine group than in the AZ vaccine group at both one and three months post-vaccination. Excellent overall concordance rates were observed between serological assays and PRNT. In a quantitative correlation analysis, the results of sVNTs showed a strong correlation with those of PRNT. Results of the four binding antibody assays showed a significant correlation with those of PRNT. The serologic assays evaluated in this study could be used as sVNTs to evaluate the efficacy of SARS-CoV-2 vaccines.

Pine Needle Extract Applicable to Topical Treatment for the Prevention of Human Papillomavirus Infection.

Most cervical cancers are associated with high-risk human papillomavirus (HPV) infection. Currently, cervical cancer treatment entails surgical removal of the lesion, but treatment of infection and preventing tissue damage are issues that still remain to be addressed. Herbal medicine and biological studies have focused on developing antiviral drugs from natural sources. In this study, we analyzed the potential antiviral effects of Pinus densiflora Sieb. et Zucc. leaf extracts against HPV. The pine needle extracts from each organic solvent were analyzed for antiviral activity. The methylene chloride fraction (PN-MC) showed the highest activity against HPV pseudovirus (PV). The PN-MC extract was more effective before, rather than after treatment, and therefore represents a prophylactic intervention. Mice were pre-treated with PN-MC via genital application or oral administration, followed by a genital or subcutaneous challenge with HPV PV, respectively. The HPV challenge results showed that mice treated via genital application exhibited complete protection against HPV. In conclusion, PN-MC represents a potential topical virucide for HPV infection.

Tannic acid-functionalized boron nitride nanosheets for theranostics.

Here, we report a tannic acid-Fe3+ coordination complex coating that confers magnetic resonance imaging (MRI) theranostic properties to inert nanomaterials. Boron nitride nanosheets (BNS), which lack magnetic field and light responsiveness, were used as a model nonfunctional nanomaterial. Among various catechol derivatives tested (i.e., dopamine, 3,4-dihydroxyphenylacetic acid, gallic acid, and tannic acid), a coating of tannic acid-Fe3+ coordination complex provided the highest magnetic field relaxivity and near infrared (NIR) laser light responsiveness. An in vitro study showed that KB tumor cells treated with tannic acid-Fe3+ coordination complex adsorbed on BNS (TA-Fe/BNS) exhibited higher T1-weighted magnetic resonance contrast compared with plain BNS, and BNS coated with tannic acid or Fe alone. NIR irradiation at 808 nm caused a significant increase in KB tumor cell death after treatment with TA-Fe/BNS compared with other treatments. In vivo MRI imaging revealed tumor accumulation of intravenously administered TA-Fe/BNS. Guided by MRI information, application of focused laser irradiation onto tumor tissues resulted in complete tumor ablation. These results support the potential of TA-Fe/BNS for MRI theranostics. Moreover, this study suggests the wide applicability of TA-Fe noncovalent coating as biocompatible and facile tool for converting nonfunctional early-generation nanomaterials into functional new nanomaterials, opening new opportunities for their use in translational biomedical applications such as MRI theranostics.

A network-based pharmacology study of active compounds and targets of Fritillaria thunbergii against influenza.

Seasonal and pandemic influenza infections are serious threats to public health and the global economy. Since antigenic drift reduces the effectiveness of conventional therapies against the virus, herbal medicine has been proposed as an alternative. Fritillaria thunbergii (FT) have been traditionally used to treat airway inflammatory diseases such as coughs, bronchitis, pneumonia, and fever-based illnesses. Herein, we used a network pharmacology-based strategy to predict potential compounds from Fritillaria thunbergii (FT), target genes, and cellular pathways to better combat influenza and influenza-associated diseases. We identified five compounds, and 47 target genes using a compound-target network (C-T). Two compounds (beta-sitosterol and pelargonidin) and nine target genes (BCL2, CASP3, HSP90AA1, ICAM1, JUN, NOS2, PPARG, PTGS1, PTGS2) were identified using a compound-influenza disease target network (C-D). Protein-protein interaction (PPI) network was constructed and we identified eight proteins from nine target genes formed a network. The compound-disease-pathway network (C-D-P) revealed three classes of pathways linked to influenza: cancer, viral diseases, and inflammation. Taken together, our systems biology data from C-T, C-D, PPI and C-D-P networks predicted potent compounds from FT and new therapeutic targets and pathways involved in influenza.

Porcine endogenous retrovirus envelope coated baculoviral DNA vaccine against porcine reproductive and respiratory syndrome virus.

PERV is a major virus concerning xenotransplantation study. However, the interesting part is that PERV is present in all kinds of pigs without pathogenicity and immune response. Furthermore, since pig cells have receptors for PERV, the gene delivery system using PERV envelope is highly likely to develop into an excellent viral vector in pigs. We developed a recombinant baculovirus with a modified surface for expressing the porcine endogenous retrovirus (PERV) envelope. Porcine reproductive and respiratory syndrome virus (PRRSV) infection is a severe concern in the porcine industry due to reproduction failure and respiratory symptoms. GP5 and M proteins are major immunogenic proteins of PRRSV. Using PERV-modified baculovirus (Ac mPERV) as a delivery vector, we constructed a dual antigen (GP5 and M)-encoding DNA vaccine system, Ac mPERV-C5/C6. Intramuscular immunization in mice and pigs, Ac mPERV-C5/C6 induced comparative high humoral and cellular immune responses. Our results support further development of Ac mPERV-C5/C6 as a potential PRRSV vaccine in the porcine industry. In addition, the Ac mPERV system may be applied to the generation of other effective DNA vaccines against porcine viral diseases.

High Molecular Weight Chitosan-Complexed RNA Nanoadjuvant for Effective Cancer Immunotherapy.

Nucleic acid-based adjuvants have recently emerged as promising candidates for use in cancer vaccines to induce tumor-suppressing immune cells. In this study, we tested whether complexation of a nucleic acid-based adjuvant with chitosan (CTS) modulates immune adjuvant functions. As a nucleic acid-based adjuvant, we used toll-like receptor 3-recognizing RNA adjuvant (RA). Negatively charged RA formed nanoscale polyplexes with cationic CTS that possessed positive zeta potentials. RA/CTS polyplexes exerted dendritic cell (DC)-maturation effects without causing significant DC toxicity. This DC-maturation effect was CTS molecular weight dependent, with RA/CTS polyplexes with a CTS molecular weight of 340 kDa (RA/CTS 340K) producing the greatest effect. Subcutaneous injection of RA/CTS 340K polyplexes with the model tumor antigen ovalbumin exerted a preventive effect against challenge by ovalbumin-expressing tumor cells. It also provided greater inhibitory effects against a second challenge with the same tumor cells compared with other treatments. These protective effects of subcutaneous RA/CTS polyplex treatment were associated with the highest tumor antigen-specific humoral and cellular immune responses after tumor challenge, and with the greatest infiltration of CD4 helper T cell and CD8 T cell into the tumor tissues. Mice vaccinated with ovalbumin and RA/CTS polyplexes showed complete survival, even after repeated challenge with tumor cells. Our results suggest the potential of RA/CTS polyplexes as effective nanoadjuvants in the design of tumor vaccines and cancer immunotherapy.

Safety and photochemotherapeutic application of poly(γ-glutamic acid)-based biopolymeric nanoparticle.

The safety of nanomaterials, a crucial consideration for clinical translation, is enhanced by using building blocks that are biologically nontoxic. Here, we used poly(γ-glutamic acid) (γ-PGA) and dopamine as building blocks of polymeric nanomaterials for carrying hydrophobic anticancer drugs. The introduction of phenylalanine onto γ-PGA enabled the resulting amphiphilic derivative of γ-PGA acid to self-assemble in the presence of the anticancer drug paclitaxel (PTX) to form PTX-encapsulated micelles. The surfaces of PTX-loaded micelles were then coated with polymerized dopamine (PDA). The PDA-coated, amphiphilic γ-PGA-based micelles (AM) carrying PTX (PDA/AM/P) exerted near-infrared-responsive photothermal effects. Near-infrared irradiation of cancer cells treated with PDA/AM/P nanoparticles produced a greater anticancer effect than that observed in other treatment groups, indicating a synergistic effect. Intravenous administration of PDA/AM/P completely ablated tumors and prevented their recurrence. Notably, the in vivo safety profile of PDA/AM/P nanoparticles allowed PTX to be delivered at a 3.6-fold higher dose than was possible with PTX solubilized in surfactant, and circumvented the side effects of the surfactant. These results support the multifunctional potential of PDA/AM for the delivery of various hydrophobic drugs and imaging dyes for safe translation of nanomaterials into the clinic.

Development of a Specific CHIKV-E2 Monoclonal Antibody for Chikungunya Diagnosis.

Chikungunya fever is a vector-borne viral disease transmitted to humans by chikungunya virus (CHIKV)-infected mosquitoes. There have been many outbreaks of CHIKV infection worldwide, and the virus poses ongoing risks to global health. To prevent and control CHIKV infection, it is important to improve the current CHIKV diagnostic approaches to allow for the detection of low CHIKV concentrations and to correctly distinguish CHIKV infections from those due to other mosquito-transmitted viruses, including dengue virus (DENV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV). Here, we produced monoclonal antibodies (mAbs) against the CHIKV envelope 2 protein (CHIKV-E2) and compared their sensitivity and specificity with commercially available mAbs using enzyme-linked immunosorbent assays (ELISA). Two anti-CHIKV-E2 mAbs, 19-1 and 21-1, showed higher binding affinities to CHIKV-E2 protein than the commercial mAbs did. In particular, the 19-1 mAb had the strongest binding affinity to inactivated CHIKV. Moreover, the 19-1 mAb had very little cross-reactivity with other mosquito-borne viruses, such as ZIKV, JEV, and DENV. These results suggest that the newly produced anti-CHIKV-E2 mAb, 19-1, could be used for CHIKV diagnostic approaches.

Construction of the safe neutralizing assay system using pseudotyped Nipah virus and G protein-specific monoclonal antibody.

Nipah virus (NiV) is a recently emerged paramyxovirus that causes acute respiratory illness and fatal encephalitis in a broad spectrum of vertebrates, including humans. Due to its high pathogenicity and mortality rates, NiV requires handling in biosafety level-4 (BSL-4) containment facilities and no effective vaccines or therapeutic agents are currently available. Since current diagnostic tests for detecting serum neutralizing antibodies against NiV mainly employ live viruses, establishment of more safe and robust alternative diagnostic methods is an essential medical requirement. Here, we have developed a pseudotyped NiV and closely related Hendra virus (HeV) expressing envelope attachment (G) and fusion (F) glycoproteins using the Moloney murine leukemia virus (MuLV) packaging system. We additionally generated polyclonal antibodies (pAbs) against NiV-G and HeV-G and assessed their neutralizing activities for potential utilization in the pseudovirus-based neutralization assay and further application in the serum diagnostic test. To enhance the specificity of neutralizing antibody and sensitivity of the serological diagnostic test, monoclonal antibodies (mAbs) against NiV-G were generated, and among which four out of six mAb clones showed significant reactivity. Specifically, the 7G9 clone displayed the highest sensitivity. The selected mAb clones showed no cross-reactivity with HeV-G and efficient neutralizing activities against pseudotyped NiV. These results validate the safety and specificity of neutralization assays against NiV and HeV and present a useful tool to design effective vaccines and serological diagnosis.

Sequential activation of anticancer therapy triggered by tumor microenvironment-selective imaging.

The combination of imaging and anticancer therapy has recently emerged as a promising strategy. However, nonspecific imaging signals and distribution of anticancer drugs at normal tissues limit the specificity of the combination therapy. To overcome the challenges, we designed a system which can selectively visualize cancer tissues and initiate the subsequent action of therapeutic molecules in tumor microenvironment. Exploiting the overexpression of matrix metalloproteinase (MMP) in the tumor microenvironment, we designed a graphene oxide (GO)-based nanosheet system loaded with a pegylated MMP-cleavable imaging probe and an anticancer peptide shielded under the imaging probe. GO loaded with pegylated imaging probe derivative and anticancer buforin IIb peptide (IPGO/BF) was not fluorescent and BF hidden within pegylated surfaces did not exert anticancer activity. However, in tumor microenvironment, IPGO/BF selectively provided imaging by liberating pegylated fluorescent moiety. The cleavage of MMP-sensitive peptide triggered imaging signal and subsequent exposure of shielded BF on GO and enhanced its therapeutic function. SCC7 tumor-bearing mice treated with IPGO/BF exhibited selective fluorescence in tumor tissues, and greater imaging signal-dependent antitumor effects compared with other groups. The selective imaging-dependent sequential activation of anticancer therapy in tumor microenvironment would be a feasible strategy to reduce the nonspecific false-positive signals of tumor imaging and undesirable side effects of anticancer drugs at normal tissues.

Identification of peptide based B-cell epitopes in Zika virus NS1.

Zika virus (ZIKV), a mosquito-borne flavivirus that has recently emerged globally, poses a major threat to public health. To control this emerging disease, accurate diagnostics are required for monitoring current ZIKV outbreaks. Owing to the high nucleotide sequence similarity and cross-reactivity of ZIKV with other members of the Flaviviridae family, discrimination from other flavivirus infections is often difficult in endemic areas. ZIKV NS1 induces major virus-specific antibodies and is therefore utilized as a serological marker for ZIKV diagnosis. To identify ZIKV specific epitopes for clinical application, 33 NS1 peptides that are 15-30 amino acid in length covering whole NS1 were synthesized and analyzed linear B-cell epitopes with 38 human serum samples (20 ZIKV-positive and 18 ZIKV-negative). As a result of screening, eight epitope regions were identified. In particular, the Z8 and Z14 peptides located in the ß-ladder surface region showed higher levels of binding activity in ZIKV-positive sera without cross-reactivity to other flaviviruses. These identified sensitive and specific epitopes provide a tool for design of diagnostics and structure-based vaccine antigens for ZIKV infection.

Light-switchable systems for remotely controlled drug delivery.

Light-switchable systems have recently received attention as a new mode of remotely controlled drug delivery. In the past, a multitude of nanomedicine studies have sought to enhance the specificity of drug delivery to target sites by focusing on receptors overexpressed on malignant cells or environmental features of diseases sites. Despite these immense efforts, however, there are few clinically available nanomedicines. We need a paradigm shift in drug delivery. One strategy that may overcome the limitations of pathophysiology-based drug delivery is the use of remotely controlled delivery technology. Unlike pathophysiology-based active drug targeting strategies, light-switchable systems are not affected by the heterogeneity of cells, tissue types, and/or microenvironments. Instead, they are triggered by remote light (i.e., near-infrared) stimuli, which are absorbed by photoresponsive molecules or three-dimensional nanostructures. The sequential conversion of light to heat or reactive oxygen species can activate drug release and allow it to be spatio-temporally controlled. Light-switchable systems have been used to activate endosomal drug escape, modulate the release of chemical and biological drugs, and alter nanoparticle structures to control the release rates of drugs. This review will address the limitations of pathophysiology-based drug delivery systems, the current status of light-based remote-switch systems, and future directions in the application of light-switchable systems for remotely controlled drug delivery.

Fusion of flagellin 2 with bivalent white spot syndrome virus vaccine increases survival in freshwater shrimp.

Despite large economic losses attributable to white spot syndrome virus (WSSV), an infectious pathogen of penaeid shrimp and other crustaceans worldwide, no efficient vaccines or antiviral agents to control the virus are available at present. Here, we designed and constructed baculovirus-based vaccines delivering genes encoding the WSSV envelope proteins, VP28 and VP19. To enhance the immunogenicity of the baculovirus-based vaccine, we fused a Salmonella typhimurium flagellin 2 (FL2) gene with VP28 or VP19 gene. Both vaccine constructs elicited similar high titlers of anti-WSSV IgG after oral immunization in mice. The protective effect of oral vaccines upon WSSV challenge was observed in Macrobrachium nipponense. Bivalent vaccine displaying WSSV envelope proteins, VP19 and VP28, led to enhanced more than 10% survival protection against WSSV infection, compared to monovalent vaccine containing WSSV envelope protein, VP19 or VP28. Furthermore, a baculovirus-based WSSV vaccine fused with FL2 gene, Ac-VP28-ie1VP19FL2, efficiently protected mice against WSSV challenge (89.5% survival rate). In support of the efficacy of FL2 in our vaccine, we verified FL2 enhanced survival rate and induced the NF-κB gene in Palaemon paucidens. The collective results strongly suggest that our recombinant baculoviral system displaying WSSV envelope protein and delivering FL2-fused WSSV envelope gene effectively induced protective responses, supporting the utility of a potential new oral DNA vaccine against WSSV.

Transmission of Porcine Endogenous Retrovirus Produced from Different Recipient Cells In Vivo.

Humanized pigs have been developed to reduce the incidence of immune rejection in xenotransplantation, but significant concerns remain, such as transmission of viral zoonosis. Porcine endogenous retroviruses (PERV), which exist in the genome of pigs, are produced as infectious virions from all porcine cells and cause zoonosis. Here, we examined the possibility of zoonosis of hosts under conditions of immune suppression or xenotransplantation of cells producing host-adapted viruses. Upon transplantation of PERV-producing porcine cells into mice, no transmission of PERV was detected, whereas, transmission of PERV from mice transplanted with mouse-adapted PERV-producing cells was detected. In addition, the frequency of PERV transmission was increased in CsA treated mice transplanted with PERV-producing murine cells, compared with PERV-producing porcine cells. Transmission of PERV to host animals did not affect weight but immune responses, in particular, the number of T cells from PERV-transmitted mice, were notably reduced. The observed risk of PERV zoonosis highlights the requirement for thorough evaluation of viral zoonosis under particular host conditions, such as immunosuppressive treatment and transplantation with host-adapted virus-producing cells.

Comparison of Repellency Effect of Mosquito Repellents for DEET, Citronella, and Fennel Oil.

To confirm that Korean Food and Drug Administration (KFDA) guidelines are applicable to test the efficacy of mosquito repellents, these guidelines were used to test the efficacy and complete protection times (CPTs) of three representative mosquito repellents: N,N-diethyl-3-methylbenzamide (DEET), citronella, and fennel oil. The repellency of citronella oil decreased over time, from 97.9% at 0 h to 71.4% at 1 h and 57.7% at 2 h, as did the repellency of fennel oil, from 88.6% at 0 h to 61.2% at 1 h and 47.4% at 2 h. In contrast, the repellency of DEET remained over 90% for 6 h. The CPT of DEET (360 min) was much longer than the CPTs of citronella (10.5 min) and fennel oil (8.4 min). These results did not differ significantly from previous findings, and hence confirm that the KFDA guidelines are applicable for testing the efficacy of mosquito repellents.