International Journal of Environmental Research and Public Health

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17 pages, 3728 KiB

Open AccessArticle

Integrated Pangenome Analysis and Pharmacophore Modeling Revealed Potential Novel Inhibitors against Enterobacter xiangfangensis

by Mohammed S. Almuhayawi, Soad K. Al Jaouni, Samy Selim, Dalal Hussien M. Alkhalifah, Romina Alina Marc, Sidra Aslam and Peter Poczai

Int. J. Environ. Res. Public Health 2022, 19(22), 14812; https://doi.org/10.3390/ijerph192214812 - 10 Nov 2022

Cited by 1 | Viewed by 1586

Abstract

Enterobacter xiangfangensis is a novel, multidrug-resistant pathogen belonging to the Enterobacter genus and has the ability to acquire resistance to multiple antibiotic classes. However, there is currently no registered E. xiangfangensis drug on the market that has been shown to be effective. Hence, [...] Read more.

Enterobacter xiangfangensis is a novel, multidrug-resistant pathogen belonging to the Enterobacter genus and has the ability to acquire resistance to multiple antibiotic classes. However, there is currently no registered E. xiangfangensis drug on the market that has been shown to be effective. Hence, there is an urgent need to identify novel therapeutic targets and effective treatments for E. xiangfangensis. In the current study, a bacterial pan genome analysis and subtractive proteomics approach was employed to the core proteomes of six strains of E. xiangfangensis using several bioinformatic tools, software, and servers. However, 2611 nonredundant proteins were predicted from the 21,720 core proteins of core proteome. Out of 2611 nonredundant proteins, 372 were obtained from Geptop2.0 as essential proteins. After the subtractive proteomics and subcellular localization analysis, only 133 proteins were found in cytoplasm. All cytoplasmic proteins were examined using BLASTp against the virulence factor database, which classifies 20 therapeutic targets as virulent. Out of these 20, 3 cytoplasmic proteins: ferric iron uptake transcriptional regulator (FUR), UDP-2,3diacylglucosamine diphosphatase (UDP), and lipid-A-disaccharide synthase (lpxB) were chosen as potential drug targets. These drug targets are important for bacterial survival, virulence, and growth and could be used as therapeutic targets. More than 2500 plant chemicals were used to molecularly dock these proteins. Furthermore, the lowest-binding energetic docked compounds were found. The top five hit compounds, Adenine, Mollugin, Xanthohumol C, Sakuranetin, and Toosendanin demonstrated optimum binding against all three target proteins. Furthermore, molecular dynamics simulations and MM/GBSA analyses validated the stability of ligand–protein complexes and revealed that these compounds could serve as potential E. xiangfangensis replication inhibitors. Consequently, this study marks a significant step forward in the creation of new and powerful drugs against E. xiangfangensis. Future studies should validate these targets experimentally to prove their function in E. xiangfangensis survival and virulence. Full article

(This article belongs to the Special Issue Clinical Microbiology and Infectious Diseases)

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13 pages, 781 KiB

Open AccessArticle

Prevalence of Antimicrobial Prescribing in Long-Term Care Facilities in a Local Health Authority of Northern Italy

by Andrea Sarro, Francesco Di Nardo, Michela Andreoletti, Chiara Airoldi, Lorenza Scotti and Massimiliano Panella

Int. J. Environ. Res. Public Health 2022, 19(20), 13412; https://doi.org/10.3390/ijerph192013412 - 17 Oct 2022

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Abstract

Background: Almost half of antimicrobial prescriptions in long-term care facilities (LTCFs) is inappropriate. This broad use might represent a strong contributor to antimicrobial resistance in these facilities. This study aimed to assess antibiotic use patterns and potential associated factors with a survey of [...] Read more.

Background: Almost half of antimicrobial prescriptions in long-term care facilities (LTCFs) is inappropriate. This broad use might represent a strong contributor to antimicrobial resistance in these facilities. This study aimed to assess antibiotic use patterns and potential associated factors with a survey of LTCFs in the local health authority (LHA) of Novara. Methods: A cross-sectional study was conducted in 25 LTCFs in the LHA of Novara following the healthcare-associated infection in LCTFs (HALT) protocol. Information on residents and facilities was assessed. Antibiotic usage and potential determinants were also estimated. Results: In total, 1137 patients were screened for antibiotic usage. Mean age was 84.58 years (SD 9.77), and the majority were female (76.52%). Twenty-six were antibiotic users (prevalence rate 2.29%, 95%CI 1.50–3.33). Antimicrobials were mainly prescribed orally (84.62%). Potential risk factors for antibiotic prescription were catheter use (central and peripheral venous, p-values 0.0475 and 0.0034, respectively, and urinary, p-value 0.0008), immobilization (p-value < 0.0001), and sex (p-value 0.0486). Conclusions: This study identified a low prevalence of antimicrobic consumption in LTCFs. Further surveillance studies are warranted to identify trends and changes in pathogen incidence and antimicrobial resistance and to inform public health authorities on the necessity of prudent use of antimicrobials in LCTFs. Full article

(This article belongs to the Special Issue Clinical Microbiology and Infectious Diseases)

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21 pages, 6481 KiB

Open AccessArticle

mRNA-Based Vaccine Designing against Epstein-Barr Virus to Induce an Immune Response Using Immunoinformatic and Molecular Modelling Approaches

by Hassan N. Althurwi, Khalid M. Alharthy, Faisal F. Albaqami, Ali Altharawi, Muhammad Rizwan Javed, Ziyad Tariq Muhseen and Muhammad Tahir ul Qamar

Int. J. Environ. Res. Public Health 2022, 19(20), 13054; https://doi.org/10.3390/ijerph192013054 - 11 Oct 2022

Cited by 7 | Viewed by 2595

Abstract

Epstein-Barr Virus (EBV) is a human pathogen that has a morbidity rate of 90% in adults worldwide. Infectious mononucleosis is caused by EBV replication in B cells and epithelial cells of the host. EBV has also been related to autoimmune illnesses, including multiple [...] Read more.

Epstein-Barr Virus (EBV) is a human pathogen that has a morbidity rate of 90% in adults worldwide. Infectious mononucleosis is caused by EBV replication in B cells and epithelial cells of the host. EBV has also been related to autoimmune illnesses, including multiple sclerosis and cancers like nasopharyngeal carcinomas and Burkitt’s lymphoma. Currently, no effective medications or vaccinations are available to treat or prevent EBV infection. Thus, the current study focuses on a bioinformatics approach to design an mRNA-based multi-epitope (MEV) vaccine to prevent EBV infections. For this purpose, we selected six antigenic proteins from the EBV proteome based on their role in pathogenicity to predict, extract, and analyze T and B cell epitopes using immunoinformatics tools. The epitopes were directed through filtering parameters including allergenicity, toxicity, antigenicity, solubility, and immunogenicity assessment, and finally, the most potent epitopes able to induce T and B cell immune response were selected. In silico molecular docking of prioritized T cell peptides with respective Human Leukocytes Antigens molecules, were carried out to evaluate the individual peptide’s binding affinity. Six CTL, four HTL, and ten linear B cell epitopes fulfilled the set parameters and were selected for MEV-based mRNA vaccine. The prioritized epitopes were joined using suitable linkers to improve epitope presentation. The immune simulation results affirmed the designed vaccine’s capacity to elicit a proper immune response. The MEV-based mRNA vaccine constructed in this study offers a promising choice for a potent vaccine against EBV. Full article

(This article belongs to the Special Issue Clinical Microbiology and Infectious Diseases)

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11 pages, 1003 KiB

Open AccessArticle

Epidemiology of Human Adenovirus in Pakistani Children Hospitalized with Community-Acquired Gastroenteritis under the Age of Five Years

by Nazif Ullah Khan, Shamsullah, Shahidullah, Aamer Ali Shah, Syed Sohail Zahoor Zaidi and Zhi Chen

Int. J. Environ. Res. Public Health 2022, 19(19), 12534; https://doi.org/10.3390/ijerph191912534 - 01 Oct 2022

Cited by 4 | Viewed by 2066

Abstract

Acute gastroenteritis is the major cause of morbidity and mortality among infants and children around the globe. Along with other enteropathogens, human adenovirus (HadV) is a major etiological agent associated with diarrhea in young children. However, information about the epidemiology of Adenoviruses in [...] Read more.

Acute gastroenteritis is the major cause of morbidity and mortality among infants and children around the globe. Along with other enteropathogens, human adenovirus (HadV) is a major etiological agent associated with diarrhea in young children. However, information about the epidemiology of Adenoviruses in Pakistan is limited or has not been reported. A total of 1082 stool samples were collected from patients with acute gastroenteritis under the age of five years with symptoms of diarrhea, vomiting, nausea, and abdominal cramps who visited Benazir Bhutto Hospital Rawalpindi and Children’s hospital in Lahore of Punjab Province in Pakistan. Of this, 384 cases with no blood in their stool, negative for Rotavirus, and under the age of five years were recruited in this study. Human Adenoviruses were isolated in the human epithelial HEp-2 cell line. Furthermore, adenovirus antigen detection was carried out by an enzyme-linked immunosorbent assay (ELISA), and then all positive and negative samples were confirmed by nested PCR. After inoculating a clear stool supernatant on HEp-2 cell lines, we observed a positive cytopathic effect in 65 (16%) cases. Using an enzyme-linked immunosorbent assay, HAdV antigens were detected in 54 (14.06%) of the clear supernatant from gastroenteritis cases. However, HAdV hexon coding regions were amplified in 57 (14.80%) fecal samples, mainly from patients ≤24 months of age. The findings of this study suggest that adenovirus circulates significantly in the children population under the age of five years and may be the potential etiological factor of acute gastroenteritis in the mentioned cities. This study provides baseline data about the possible role of adenovirus in causing viral diarrhea in children. Further large-scale epidemiological surveys are recommended to better understand disease burden, etiological agents, and its clinical impact across the country. Full article

(This article belongs to the Special Issue Clinical Microbiology and Infectious Diseases)

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15 pages, 1734 KiB

Open AccessArticle

Novel Chimeric Vaccine Candidate Development against Leptotrichia buccalis

by Abdulrahman Alshammari, Abdullah F. Alasmari, Metab Alharbi, Nemat Ali, Ziyad Tariq Muhseen, Usman Ali Ashfaq, Miraj Ud-din, Asad Ullah, Muhammad Arshad and Sajjad Ahmad

Int. J. Environ. Res. Public Health 2022, 19(17), 10742; https://doi.org/10.3390/ijerph191710742 - 29 Aug 2022

Cited by 2 | Viewed by 1277

Abstract

The misuse of antibiotics in our daily lives has led to the emergence of antimicrobial resistance. As a result, many antibiotics are becoming ineffective. This phenomenon is linked with high rates of mortality and morbidity. Therefore, new approaches are required to address this [...] Read more.

The misuse of antibiotics in our daily lives has led to the emergence of antimicrobial resistance. As a result, many antibiotics are becoming ineffective. This phenomenon is linked with high rates of mortality and morbidity. Therefore, new approaches are required to address this major health issue. Leptotrichia buccalis is a Gram-negative, rod-shaped bacterium which normally resides in the oral and vaginal cavities. It is an emerging bacterial pathogen which is developing new antibiotic-resistance mechanisms. No approved vaccine is available against this pathogen, which is a cause for growing concern. In this study, an in silico-based, multi-epitopes vaccine against this pathogen was designed by applying reverse vaccinology and immunoinformatic approaches. Of a total of 2193 predicted proteins, 294 were found to be redundant while 1899 were non-redundant. Among the non-redundant proteins, 6 were predicted to be present in the extracellular region, 12 in the periplasmic region and 23 in the outer-membrane region. Three proteins (trypsin-like peptidase domain-containing protein, sel1 repeat family protein and TrbI/VirB10 family protein) were predicted to be virulent and potential subunit vaccine targets. In the epitopes prediction phase, the three proteins were subjected to B- and T-cell epitope mapping; 19 epitopes were used for vaccine design. The vaccine construct was docked with MHC-I, MHC-II and TLR-4 immune receptors and only the top-ranked complex (based on global energy value) was selected in each case. The selected docked complexes were examined in a molecular dynamic simulation and binding free energies analysis in order to assess their intermolecular stability. It was observed that the vaccine binding mode with receptors was stable and that the system presented stable dynamics. The net binding free energy of complexes was in the range of −300 to −500 kcal/mol, indicating the formation of stable complexes. In conclusion, the data reported herein might help vaccinologists to formulate a chimeric vaccine against the aforementioned target pathogen. Full article

(This article belongs to the Special Issue Clinical Microbiology and Infectious Diseases)

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23 pages, 3884 KiB

Open AccessArticle

Pan-Genome Analysis of Oral Bacterial Pathogens to Predict a Potential Novel Multi-Epitopes Vaccine Candidate

by Tehniyat Rida, Sajjad Ahmad, Asad Ullah, Saba Ismail, Muhammad Tahir ul Qamar, Zobia Afsheen, Muhammad Khurram, Muhammad Saqib Ishaq, Ali G. Alkhathami, Eid A. Alatawi, Faris Alrumaihi and Khaled S. Allemailem

Int. J. Environ. Res. Public Health 2022, 19(14), 8408; https://doi.org/10.3390/ijerph19148408 - 09 Jul 2022

Cited by 16 | Viewed by 2405

Abstract

Porphyromonas gingivalis is a Gram-negative anaerobic bacterium, mainly present in the oral cavity and causes periodontal infections. Currently, no licensed vaccine is available against P. gingivalis and other oral bacterial pathogens. To develop a vaccine against P. gingivalis, herein, we applied a [...] Read more.

Porphyromonas gingivalis is a Gram-negative anaerobic bacterium, mainly present in the oral cavity and causes periodontal infections. Currently, no licensed vaccine is available against P. gingivalis and other oral bacterial pathogens. To develop a vaccine against P. gingivalis, herein, we applied a bacterial pan-genome analysis (BPGA) on the bacterial genomes that retrieved a total number of 4908 core proteins, which were further utilized for the identification of good vaccine candidates. After several vaccine candidacy analyses, three proteins, namely lytic transglycosylase domain-containing protein, FKBP-type peptidyl-propyl cis-trans isomerase and superoxide dismutase, were shortlisted for epitopes prediction. In the epitopes prediction phase, different types of B and T-cell epitopes were predicted and only those with an antigenic, immunogenic, non-allergenic, and non-toxic profile were selected. Moreover, all the predicted epitopes were joined with each other to make a multi-epitopes vaccine construct, which was linked further to the cholera toxin B-subunit to enhance the antigenicity of the vaccine. For downward analysis, a three dimensional structure of the designed vaccine was modeled. The modeled structure was checked for binding potency with major histocompatibility complex I (MHC-I), major histocompatibility complex II (MHC-II), and Toll-like receptor 4 (TLR-4) immune cell receptors which revealed that the designed vaccine performed proper binding with respect to immune cell receptors. Additionally, the binding efficacy of the vaccine was validated through a molecular dynamic simulation that interpreted strong intermolecular vaccine–receptor binding and confirmed the exposed situation of vaccine epitopes to the host immune system. In conclusion, the study suggested that the model vaccine construct has the potency to generate protective host immune responses and that it might be a good vaccine candidate for experimental in vivo and in vitro studies. Full article

(This article belongs to the Special Issue Clinical Microbiology and Infectious Diseases)

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21 pages, 6332 KiB

Open AccessArticle

Computer-Aided Multi-Epitope Vaccine Design against Enterobacter xiangfangensis

by Abdulrahman Alshammari, Metab Alharbi, Abdullah Alghamdi, Saif Ali Alharbi, Usman Ali Ashfaq, Muhammad Tahir ul Qamar, Asad Ullah, Muhammad Irfan, Amjad Khan and Sajjad Ahmad

Int. J. Environ. Res. Public Health 2022, 19(13), 7723; https://doi.org/10.3390/ijerph19137723 - 23 Jun 2022

Cited by 14 | Viewed by 2422

Abstract

Antibiotic resistance is a global public health threat and is associated with high mortality due to antibiotics’ inability to treat bacterial infections. Enterobacter xiangfangensis is an emerging antibiotic-resistant bacterial pathogen from the Enterobacter genus and has the ability to acquire resistance to multiple [...] Read more.

Antibiotic resistance is a global public health threat and is associated with high mortality due to antibiotics’ inability to treat bacterial infections. Enterobacter xiangfangensis is an emerging antibiotic-resistant bacterial pathogen from the Enterobacter genus and has the ability to acquire resistance to multiple antibiotic classes. Currently, there is no effective vaccine against Enterobacter species. In this study, a chimeric vaccine is designed comprising different epitopes screened from E. xiangfangensis proteomes using immunoinformatic and bioinformatic approaches. In the first phase, six fully sequenced proteomes were investigated by bacterial pan-genome analysis, which revealed that the pathogen consists of 21,996 core proteins, 3785 non-redundant proteins and 18,211 redundant proteins. The non-redundant proteins were considered for the vaccine target prioritization phase where different vaccine filters were applied. By doing so, two proteins; ferrichrome porin (FhuA) and peptidoglycan-associated lipoprotein (Pal) were shortlisted for epitope prediction. Based on properties of antigenicity, allergenicity, water solubility and DRB*0101 binding ability, three epitopes (GPAPTIAAKR, ATKTDTPIEK and RNNGTTAEI) were used in multi-epitope vaccine designing. The designed vaccine construct was analyzed in a docking study with immune cell receptors, which predicted the vaccine’s proper binding with said receptors. Molecular dynamics analysis revealed that the vaccine demonstrated stable binding dynamics, and binding free energy calculations further validated the docking results. In conclusion, these in silico results may help experimentalists in developing a vaccine against E. xiangfangensis in specific and Enterobacter in general. Full article

(This article belongs to the Special Issue Clinical Microbiology and Infectious Diseases)

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26 pages, 4210 KiB

Open AccessArticle

Vaccinomics to Design a Multi-Epitopes Vaccine for Acinetobacter baumannii

by Miraj ud-din, Aqel Albutti, Asad Ullah, Saba Ismail, Sajjad Ahmad, Anam Naz, Muhammad Khurram, Mahboob ul Haq, Zobia Afsheen, Youness El Bakri, Muhammad Salman, Bilal Shaker and Muhammad Tahir ul Qamar

Int. J. Environ. Res. Public Health 2022, 19(9), 5568; https://doi.org/10.3390/ijerph19095568 - 04 May 2022

Cited by 24 | Viewed by 3292

Abstract

Antibiotic resistance (AR) is the result of microbes’ natural evolution to withstand the action of antibiotics used against them. AR is rising to a high level across the globe, and novel resistant strains are emerging and spreading very fast. Acinetobacter baumannii is a [...] Read more.

Antibiotic resistance (AR) is the result of microbes’ natural evolution to withstand the action of antibiotics used against them. AR is rising to a high level across the globe, and novel resistant strains are emerging and spreading very fast. Acinetobacter baumannii is a multidrug resistant Gram-negative bacteria, responsible for causing severe nosocomial infections that are treated with several broad spectrum antibiotics: carbapenems, β-lactam, aminoglycosides, tetracycline, gentamicin, impanel, piperacillin, and amikacin. The A. baumannii genome is superplastic to acquire new resistant mechanisms and, as there is no vaccine in the development process for this pathogen, the situation is more worrisome. This study was conducted to identify protective antigens from the core genome of the pathogen. Genomic data of fully sequenced strains of A. baumannii were retrieved from the national center for biotechnological information (NCBI) database and subjected to various genomics, immunoinformatics, proteomics, and biophysical analyses to identify potential vaccine antigens against A. baumannii. By doing so, four outer membrane proteins were prioritized: TonB-dependent siderphore receptor, OmpA family protein, type IV pilus biogenesis stability protein, and OprD family outer membrane porin. Immuoinformatics predicted B-cell and T-cell epitopes from all four proteins. The antigenic epitopes were linked to design a multi-epitopes vaccine construct using GPGPG linkers and adjuvant cholera toxin B subunit to boost the immune responses. A 3D model of the vaccine construct was built, loop refined, and considered for extensive error examination. Disulfide engineering was performed for the stability of the vaccine construct. Blind docking of the vaccine was conducted with host MHC-I, MHC-II, and toll-like receptors 4 (TLR-4) molecules. Molecular dynamic simulation was carried out to understand the vaccine-receptors dynamics and binding stability, as well as to evaluate the presentation of epitopes to the host immune system. Binding energies estimation was achieved to understand intermolecular interaction energies and validate docking and simulation studies. The results suggested that the designed vaccine construct has high potential to induce protective host immune responses and can be a good vaccine candidate for experimental in vivo and in vitro studies. Full article

(This article belongs to the Special Issue Clinical Microbiology and Infectious Diseases)

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16 pages, 1388 KiB

Open AccessArticle

COVID-19 Clinical Profiles and Fatality Rates in Hospitalized Patients Reveal Case Aggravation and Selective Co-Infection by Limited Gram-Negative Bacteria

by Kamaleldin B. Said, Ahmed Alsolami, Safia Moussa, Fayez Alfouzan, Abdelhafiz I. Bashir, Musleh Rashidi, Rana Aborans, Taha E. Taha, Husam Almansour, Mashari Alazmi, Amal Al-Otaibi, Luluh Aljaloud, Basmah Al-Anazi, Ahmed Mohialdin and Ahmed Aljadani

Int. J. Environ. Res. Public Health 2022, 19(9), 5270; https://doi.org/10.3390/ijerph19095270 - 26 Apr 2022

Cited by 16 | Viewed by 2731

Abstract

Bacterial co-infections may aggravate COVID-19 disease, and therefore being cognizant of other pathogens is imperative. We studied the types, frequency, antibiogram, case fatality rates (CFR), and clinical profiles of co-infecting-pathogens in 301 COVID-19 patients. Co-infection was 36% (n = 109), while CFR [...] Read more.

Bacterial co-infections may aggravate COVID-19 disease, and therefore being cognizant of other pathogens is imperative. We studied the types, frequency, antibiogram, case fatality rates (CFR), and clinical profiles of co-infecting-pathogens in 301 COVID-19 patients. Co-infection was 36% (n = 109), while CFR was 31.2% compared to 9.9% in non-co-infected patients (z-value = 3.1). Four bacterial species dominated, namely, multidrug-resistant Klebsiella pneumoniae (37%, n = 48), extremely drug-resistant Acinetobacter baumannii (26%, n = 34), multidrug-resistant Eschericia. coli (18.6%, n = 24), and extremely drug-resistant Pseudomonas aeruginosa (8.5%, n = 11), in addition to other bacterial species (9.3%, n = 12). Increased co-infection of K. pneumoniae and A. baumannii was associated with increased death rates of 29% (n = 14) and 32% (n = 11), respectively. Klebsiella pneumoniae was equally frequent in respiratory and urinary tract infections (UTI), while E. coli mostly caused UTI (67%), and A. baumannii and P. aeruginosa dominated respiratory infections (38% and 45%, respectively). Co-infections correlated with advance in age: seniors ≥ 50 years (71%), young adults 21–49 years (25.6%), and children 0–20 years (3%). These findings have significant clinical implications in the successful COVID-19 therapies, particularly in geriatric management. Future studies would reveal insights into the potential selective mechanism(s) of Gram-negative bacterial co-infection in COVID-19 patients. Full article

(This article belongs to the Special Issue Clinical Microbiology and Infectious Diseases)

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19 pages, 3517 KiB

Open AccessArticle

Designing of a Recombinant Multi-Epitopes Based Vaccine against Enterococcus mundtii Using Bioinformatics and Immunoinformatics Approaches

by Metab Alharbi, Abdulrahman Alshammari, Abdullah F. Alasmari, Salman Mansour Alharbi, Muhammad Tahir ul Qamar, Asad Ullah, Sajjad Ahmad, Muhammad Irfan and Atif Ali Khan Khalil

Int. J. Environ. Res. Public Health 2022, 19(6), 3729; https://doi.org/10.3390/ijerph19063729 - 21 Mar 2022

Cited by 26 | Viewed by 3275

Abstract

Enterococcus species are an emerging group of bacterial pathogens that have a significant role in hospital-associated infections and are associated with higher mortality and morbidity rates. Among these pathogens, Enterococcus mundtii is one of the causative agents of multiple hospital associated infections. Currently, [...] Read more.

Enterococcus species are an emerging group of bacterial pathogens that have a significant role in hospital-associated infections and are associated with higher mortality and morbidity rates. Among these pathogens, Enterococcus mundtii is one of the causative agents of multiple hospital associated infections. Currently, no commercially available licensed vaccine is present, and multi-drug resistant strains of the pathogen are prominent. Due to several limitations of experimental vaccinology, computational vaccine designing proved to be helpful in vaccine designing against several bacterial pathogens. Herein, we designed a multi-epitope-based vaccine against E. mundtii using in silico approaches. After an in-depth analysis of the core genome, three probable antigenic proteins (lytic polysaccharide monooxygenase, siderophore ABC transporter substrate-binding protein, and lytic polysaccharide monooxygenase) were shortlisted for epitope prediction. Among predicted epitopes, ten epitopes—GPADGRIAS, TTINHGGAQA, SERTALSVTT, GDGGNGGGEV, GIKEPDLEK, KQADDRIEA, QAIGGDTSN, EPLDEQTASR, AQWEPQSIEA, QPLKFSDFEL—were selected for multi-epitope vaccine construct designing. The screened B- and T-cell epitopes were joined with each other via specific linkers and linked to the cholera toxin B subunit as an adjuvant to enhance vaccine immune protection efficacy. The designed vaccine construct induced cellular and humoral immune responses. Blind docking with immune cell receptors, followed by molecular dynamic simulation results confirms the good binding potency and stability of the vaccine in providing protection against the pathogen. Full article

(This article belongs to the Special Issue Clinical Microbiology and Infectious Diseases)

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Jump to: Research

6 pages, 925 KiB

Open AccessCase Report

DAA Treatment Failure in a HIV/HBV/HCV Co-Infected Patient Carrying a Chimeric HCV Genotype 4/1b

by Maria Antonia De Francesco, Franco Gargiulo, Serena Zaltron, Angiola Spinetti, Francesco Castelli and Arnaldo Caruso

Int. J. Environ. Res. Public Health 2022, 19(18), 11655; https://doi.org/10.3390/ijerph191811655 - 15 Sep 2022

Viewed by 1457

Abstract

Approved direct antiviral agent (DAA) combinations are associated with high rates of sustained virological response (SVR) and the absence of a detectable hepatitis C viral load 12–24 weeks after treatment discontinuation. However, a low percentage of individuals fail DAA therapy. Here, we report [...] Read more.

Approved direct antiviral agent (DAA) combinations are associated with high rates of sustained virological response (SVR) and the absence of a detectable hepatitis C viral load 12–24 weeks after treatment discontinuation. However, a low percentage of individuals fail DAA therapy. Here, we report the case of a HIV/HBV/HCV co-infected patient who failed to respond to DAA pangenotypic combination therapy. The sequencing of NS5a, NS5b, NS3 and core regions evidenced a recombinant intergenotypic strain 4/1b with a recombination crossover point located inside the NS3 region. The identification of this natural recombinant virus underlines the concept that HCV recombination, even if it occurs rarely, may play a key role in the virus fitness and evolution. Full article

(This article belongs to the Special Issue Clinical Microbiology and Infectious Diseases)

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