• Journal of Preventive Medicine and Public Health
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• v.55 no.2
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• pp.134-143
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• 2022

Objectives: Many governments have imposed-and are still imposing-mobility restrictions to contain the coronavirus disease 2019 (COVID-19) pandemic. However, there is no consensus on whether policy-induced reductions of human mobility effectively reduce the effective reproduction number (Rt) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several studies based on country-restricted data reported conflicting trends in the change of the SARS-CoV-2 Rt following mobility restrictions. The objective of this study was to examine, at the global scale, the existence of regional specificities in the correlations between Rt and human mobility. Methods: We computed the Rt of SARS-CoV-2 using data on worldwide infection cases reported by the Johns Hopkins University, and analyzed the correlation between Rt and mobility indicators from the Google COVID-19 Community Mobility Reports in 125 countries, as well as states/regions within the United States, using the Pearson correlation test, linear modeling, and quadratic modeling. Results: The correlation analysis identified countries where Rt negatively correlated with residential mobility, as expected by policymakers, but also countries where Rt positively correlated with residential mobility and countries with more complex correlation patterns. The correlations between Rt and residential mobility were non-linear in many countries, indicating an optimal level above which increasing residential mobility is counterproductive. Conclusions: Our results indicate that, in order to effectively reduce viral circulation, mobility restriction measures must be tailored by region, considering local cultural determinants and social behaviors. We believe that our results have the potential to guide differential refinement of mobility restriction policies at a country/regional resolution.

• Journal of Veterinary Science
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• v.24 no.5
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• pp.54.1-54.13
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• 2023

Background: Porcine reproductive and respiratory syndrome virus (PRRSV) vaccines do not provide full cross-protection, mainly due to the virus genetic variability. Despite this, vaccines based on modified-live PRRSV (PRRSV-MLV) reduce the disease impact. Objectives: To assess the efficacy of two commercial vaccines-one based on PRRSV1 (PRRSV1-MLV) and another on PRRSV2 (PRRSV2-MLV)-against a Japanese PRRSV2 field strain. Methods: Two groups of three-week-old piglets were vaccinated (G1: PRRSV1-MLV; G2: PRRSV2-MLV) and two were kept as non-vaccinated (INF and CTRL). One month later, G1, G2, and INF were challenged with a PRRSV2 field strain. Results: After the challenge, clinical signs were only observed in INF. Moreover, the highest rectal temperatures and values for the area under the curve (AUC) were observed in INF. Regarding viral detection, both AUC and the proportion of positive samples in blood were higher in INF. In G1, viremic animals never reached 100%. At necropsy (21 d after the challenge), differences for titers among groups were only found in tonsils (G1 < G2 and INF). One animal (belonging to G1) was negative in all tissues. Regarding humoral responses, G1 and G2 seroconverted after vaccination, as detected in the corresponding enzyme-linked immunosorbent assay. Specific neutralizing antibodies (NA) against PRRSV1-MLV were already detected at 14 d after vaccination in G1, showing a significant booster after the challenge, while PRRSV2-MLV NA were detected in G2 at the end of the experiment. Conclusions: Despite genetic differences, PRRSV1-MLV has been demonstrated to confer partial protection against a Japanese PRRSV2 strain, at least as good as PRRSV2-MLV.

• Genomics & Informatics
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• v.21 no.3
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• pp.34.1-34.10
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• 2023

Nosocomial infections, commonly referred to as healthcare-associated infections, are illnesses that patients get while hospitalized and are typically either not yet manifest or may develop. One of the most prevalent nosocomial diseases in hospitalized patients is pneumonia, among the leading causes of mortality and morbidity. Viral, bacterial, and fungal pathogens cause pneumonia. More severe introductions commonly included Staphylococcus aureus, which is at the top of bacterial infections, per World Health Organization reports. The staphylococci, S. aureus, strain RMI-014804, mesophile, on-sporulating, and non-motile bacterium, was isolated from the sputum of a pulmonary patient in Pakistan. Many characteristics of S. aureus strain RMI-014804 have been revealed in this paper, with complete genome sequence and annotation. Our findings indicate that the genome is a single circular 2.82 Mbp long genome with 1,962 protein-coding genes, 15 rRNA, 49 tRNA, 62 pseudogenes, and a GC content of 28.76%. As a result of this genome sequencing analysis, researchers will fully understand the genetic and molecular basis of the virulence of the S. aureus bacteria, which could help prevent the spread of nosocomial infections like pneumonia. Genome analysis of this strain was necessary to identify the specific genes and molecular mechanisms that contribute to its pathogenicity, antibiotic resistance, and genetic diversity, allowing for a more in-depth investigation of its pathogenesis to develop new treatments and preventive measures against infections caused by this bacterium.

• IMMUNE NETWORK
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• v.22 no.6
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• pp.48.1-48.13
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• 2022

With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, which are randomly mutated, the dominant strains in regions are changing globally. The development of preclinical animal models is imperative to validate vaccines and therapeutics against SARS-CoV-2 variants. The objective of this study was to develop a non-human primate (NHP) model for SARS-CoV-2 Delta variant infection. Cynomolgus macaques infected with Delta variants showed infectious viruses and viral RNA in the upper (nasal and throat) and lower respiratory (lung) tracts during the acute phase of infection. After 3 days of infection, lesions consistent with diffuse alveolar damage were observed in the lungs. For cellular immune responses, all macaques displayed transient lymphopenia and neutrophilia in the early stages of infection. SARS-CoV-2 Delta variant spike protein-specific IgM, IgG, and IgA levels were significantly increased in the plasma of these animals 14 days after infection. This new NHP Delta variant infection model can be used for comparative analysis of the difference in severity between SARS-CoV-2 variants of concern and may be useful in the efficacy evaluation of vaccines and universal therapeutic drugs for mutations.

• Journal of Microbiology and Biotechnology
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• v.34 no.10
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• pp.1933-1946
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• 2024

The gut microbiome is an important and the largest endocrine organ linked to the microbes of the GI tract. The bacterial, viral and fungal communities are key regulators of the health and disease status in a host at hormonal, neurological, immunological, and metabolic levels. The useful microbes can compete with microbes exhibiting pathogenic behavior by maintaining resistance against their colonization, thereby maintaining eubiosis. As diagnostic tools, metagenomic, proteomic and genomic approaches can determine various microbial markers in clinic for early diagnosis of colorectal cancer (CRC). Probiotics are live non-pathogenic microorganisms such as lactic acid bacteria, Bifidobacteria, Firmicutes and Saccharomyces that can help maintain eubiosis when administered in appropriate amounts. In addition, the type of dietary intake contributes substantially to the composition of gut microbiome. The use of probiotics has been found to exert antitumor effects at preclinical levels and promote the antitumor effects of immunotherapeutic drugs at clinical levels. Also, modifying the composition of gut microbiota by Fecal Microbiota Transplantation (FMT), and using live lactic acid producing bacteria such as Lactobacillus, Bifidobacteria and their metabolites (termed postbiotics) can contribute to immunomodulation of the tumor microenvironment. This can lead to tumor-preventive effects at early stages and antitumor effects after diagnosis of CRC. To conclude, probiotics are presumably found to be safe to use in humans and are to be studied further to promote their appliance at clinical levels for management of CRC.

• Clinical and Experimental Vaccine Research
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• v.13 no.2
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• pp.132-145
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• 2024

Purpose: Enterovirus 71, a pathogen that causes hand-foot and mouth disease (HFMD) is currently regarded as an increasing neurotropic virus in Asia and can cause severe complications in pediatric patients with blister-like sores or rashes on the hand, feet, and mouth. Notwithstanding the significant burden of the disease, no authorized vaccine is available. Previously identified attenuated and inactivated vaccines are worthless over time owing to changes in the viral genome. Materials and Methods: A novel vaccine construct using B-cell derived T-cell epitopes from the virulent polyprotein found the induction of possible immune response. In order to boost the immune system, a beta-defensin 1 preproprotein adjuvant with EAAAK linker was added at the N-terminal end of the vaccine sequence. Results: The immunogenicity of the designed, refined, and verified prospective three-dimensional-structure of the multi-epitope vaccine was found to be quite high, exhibiting non-allergenic and antigenic properties. The vaccine candidates bound to toll-like receptor 3 in a molecular docking analysis, and the efficacy of the potential vaccine to generate a strong immune response was assessed through in silico immunological simulation. Conclusion: Computational analysis has shown that the proposed multi-epitope vaccine is possibly safe for use in humans and can elicit an immune response.

• Clinical and Experimental Vaccine Research
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• v.13 no.3
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• pp.253-258
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• 2024

Purpose: The immunogenicity of vaccines containing the canine adenovirus (CAdV) type 2 (CAdV-2) variant has not yet been reported. We prepared a novel inactivated CAdV-2 variant vaccine using the CAV2232-41 strain, and evaluated its safety and immunogenicity in raccoon dogs. Materials and Methods: The growth kinetics of CAV2232-41 were determined using Madin-Darby Canine Kidney (MDCK) cells. The nucleotide sequences of CAV2232 and CAV2232-41 were determined by next-generation sequencing. To generate the CAdV-2 variant vaccine, CAV2232-41 propagated in the MDCK cells was inactivated with 0.1% formaldehyde. Two vaccines were prepared by blending inactivated CAV2232-41 with Cabopol and Rehydragel adjuvants. Safety and immunogenicity of the CAV2232C and CAV2232R vaccines were evaluated in guinea pigs. Safety and immunogenicity of the CAV2232C vaccine were also evaluated in raccoon dogs. The virus neutralizing antibody (VNA) titer against CAV2232-41 was measured in sera collected from immunized guinea pigs and raccoon dogs. Results: CAV2232-41 showed the highest viral titer on days 4-6 post-inoculation and had a deletion in the E3 gene, which was confirmed as a CAdV-2 variant. Guinea pigs inoculated with CAV2232C showed slightly higher VNA titers than those inoculated with CAV2232R 2 weeks after booster vaccination. Raccoon dogs immunized with the CAV2232C vaccine developed high mean VNA titers, while non-vaccinated raccoon dogs were antibody-negative. Conclusion: The CAV2232C vaccine is safe and induces a protective VNA titer in raccoon dogs.

• Clinical and Experimental Vaccine Research
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• v.11 no.3
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• pp.249-263
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• 2022

Purpose: Lassa fever is a zoonotic acute viral hemorrhagic disease caused by Lassa virus (LASV). There is currently no licensed vaccine for the prevention of the disease. This study is aimed at discovering immunodominant epitopes from the envelope glycoprotein of the Lassa mammarenavirus and designing of a multi-epitope vaccine candidate (VC). Materials and Methods: The amino acid sequences of the envelope glycoprotein of 26 strains of LASV from five countries were selected. After evaluation for antigenicity, immunogenicity, allergenicity, and toxicity, immunodominant CD8, CD4, and linear B lymphocytes were also selected. The selected epitopes were modelled and a molecular docking with the appropriate major histocompatibility complex (MHC) proteins was performed. Using an adjuvant and linkers, a multi-epitope VC was designed. The VC was evaluated for its physicochemical and immunological properties and structurally refined, validated, and mutated (disulphide engineering). The complex formed by the VC and the toll-like receptor-4 receptor was subjected to molecular dynamic simulation (MDS) followed by in silico cloning in a plasmid vector. Results: A VC with 203 sequences, 22.13 kDa weight, isoelectric point of 9.85 (basic), instability index value of 27.62, aliphatic index of 68.87, and GRAVY value of -0.455 (hydrophilic) emerged. The VC is predicted to be non-allergenic with antigenicity, MHC I immunogenicity, and solubility upon overexpression values of 0.81, 2.04, and 0.86 respectively. The VC also has an estimated half-life greater than 10 hours in Escherichia coli and showed stability in all the parameters of MDS. Conclusion: The VC shows good promise in the prevention of Lassa fever but further tests are required to validate its safety and efficacy.

• Journal of Veterinary Science
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• v.25 no.5
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• pp.66.1-66.12
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• 2024

Importance: Porcine epidemic diarrhea virus (PEDV) binds to particular cell surface receptors to penetrate cells. The virus specifically identifies certain carbohydrate structures present on the surface of the cell to facilitate the binding process. Nevertheless, the influence of viral infections on specific alterations of glycoconjugates in the small intestines remains unexplored. Objective: This work aimed to examine the alterations in glycoconjugates in the small intestines of piglets naturally infected with PEDV using lectin histochemistry. Methods: Six piglets including three PEDV-infected and three non-infected piglets were evaluated. Small intestinal samples were histopathologically examined, and lectin histochemistry was performed. Results: Piglets infected with PEDV had significant histological abnormalities in their small intestines, such as pronounced villous atrophy, varying degrees of villous fusion, and diverse mucosal alterations. Specific regions of the duodenum, jejunum, and ileum showed discernible variations in glycoconjugate distribution, as determined by lectin histochemistry. Compared with the controls, the PEDV-infected piglets showed significant changes in N-acetylglucosamine- and galactose-binding lectins (particularly wheat germ agglutinin and Arachis hypogaea (peanut) agglutinin) in multiple intestinal regions. Conclusions and Relevance: These findings can enhance understanding of how viruses such as PEDV impact the glycoconjugate composition of the small intestines and emphasize the potential connection between the pathogenesis of PEDV and glycoconjugate.

• Journal of Life Science
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• v.30 no.3
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• pp.285-290
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• 2020

Foot-and-mouth disease virus (FMDV), a member of the genus Aphthovirus in the Picornaviridae family, affects wild and domesticated ruminants and pigs. FMDV causes various clinical symptoms, including severe inflammation in infected tissue. Genome RNA of FMDV shows a positive single-strand chain approximately 8.3 kb long and encodes a single long open reading frame (ORF). The ORF is translated into structural and non-structural proteins by viral proteases. The FMDV 2C protein is one of the non-structural proteins encoded by FMDV and plays a critical role in FMD pathogenesis, including inflammation, apoptosis, and viral replication. In this study, we examined whether FMDV 2C induces intracellular expression of pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). FMDV 2C expression in pig IBRS-2 cells increased mRNA and protein expression of TNFα at the transcriptional level via activation of TNFα promoter. Treatment with 4-phenylbutyric acid, an endoplasmic reticulum (ER) stress reducer, decreased TNFα expression induced by FMDV 2C. Activating transcription factor 4 (ATF4), a transcription factor mediating ER stress response, induced transactivation of TNFα promoter and expression of mRNA and protein of TNFα. However, the dominant negative mutant of ATF4 did not induce FMDV 2C-mediated TNFα expression. The results indicate that FMDV 2C protein increases clinical inflammation via ATF4-mediated TNFα expression and is associated with ER stress induction.