Virology Journal最新文献

{"title":"HBeAg-positive CHB patients with indeterminate phase associated with a high risk of significant fibrosis.","authors":"Yuanyuan Li, Yijia Zhu, Dongmei Gao, Yifan Pan, Jian Wang, Shaoqiu Zhang, Xiaomin Yan, Li Zhu, Chuanwu Zhu, Xingxiang Liu, Zhaoping Zhang, Jie Li, Yuxin Chen, Rui Huang, Chao Wu","doi":"10.1186/s12985-024-02561-1","DOIUrl":"10.1186/s12985-024-02561-1","url":null,"abstract":"<p><strong>Background: </strong>The risk of liver fibrosis in HBeAg-positive chronic hepatitis B (CHB) patients with indeterminate phase is not well characterized. We aimed to compare the presence of liver fibrosis in HBeAg-positive CHB patients between indeterminate phase and immune-tolerant phase.</p><p><strong>Methods: </strong>This multi-center, retrospective cohort study included 719 treatment-naïve HBeAg-positive CHB patients with normal alanine aminotransferase (ALT). Patients with HBV DNA > 10⁶ IU/mL were categorized into immune-tolerant phase, whereas those with HBV DNA ≤ 10⁶ IU/mL were classified into indeterminate phase. Significant liver fibrosis and cirrhosis were determined by APRI, FIB-4, transient elastography, or liver biopsy.</p><p><strong>Results: </strong>The median age of patients was 33.0 years and 59.8% of patients were male. 81.5% and 18.5% of patients were in the immune-tolerant phase and indeterminate phase, respectively. The APRI (0.33 vs. 0.27, P < 0.001), FIB-4 (1.07 vs. 0.72, P < 0.001), and liver stiffness values (7.80 kPa vs. 5.65 kPa, P = 0.011) were higher in patients with indeterminate phase than those with immune-tolerant phase. Patients in the indeterminate phase had significantly higher proportions of significant fibrosis (27.1% vs. 11.3%, P < 0.001) and cirrhosis (14.3% vs. 3.2%, P < 0.001) compared to those in the immune-tolerant phase. In the multivariate analysis, indeterminate phase (OR 2.138, 95% CI 1.253, 3.649, P = 0.005) was associated with a higher risk of significant fibrosis, especially for patients aged ≥ 30 years.</p><p><strong>Conclusion: </strong>HBeAg-positive CHB patients in the indeterminate phase had more severe liver fibrosis compared to those in the immune-tolerant phase.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"21 1","pages":"287"},"PeriodicalIF":4.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complete genome characterization by nanopore sequencing of rotaviruses A, B, and C circulating on large-scale pig farms in Russia.","authors":"Nikita Krasnikov, Alexey Gulyukin, Taras Aliper, Anton Yuzhakov","doi":"10.1186/s12985-024-02567-9","DOIUrl":"10.1186/s12985-024-02567-9","url":null,"abstract":"<p><strong>Background: </strong>Rotaviruses are the major etiological agents of gastroenteritis and diarrheal outbreaks in plenty of mammalian species. The genus Rotavirus is highly diverse and currently comprises nine genetically distinct species, and four of them (A, B, C, and H) are common for humans and pigs. There is a strong necessity to comprehend phylogenetic relationships among rotaviruses from different host species to assess interspecies transmission, specifically between humans and livestock. To reveal the genetic origin of rotaviruses from Russian pig farms, nanopore-based metagenomic sequencing was performed on the PCR-positive specimens.</p><p><strong>Methods: </strong>Samples were selected among the cases submitted to routine diagnostic or monitoring studies to the Laboratory of Biochemistry and Molecular Biology of \"Federal Scientific Center VIEV\" (Moscow, Russia). The selected positive samples were genotyped using nanopore sequencing method.</p><p><strong>Results: </strong>Five porcine RVA isolates were completely sequenced, and genotype analysis revealed various porcine G/P genogroups: G2, G3, G4, G5, G11 and P[6], P[7], P[13], P[23], P[27] with a typical backbone constellation I5-R1-C1-M1-A8-N1-T1/7-E1-H1. The RVB isolate was detected in combination with RVA in a rectal swab from a diseased pig in Krasnoyarsk Krai. It was characterized by the following genogroups: G15-P[X]-I11-R4-C4-M4-A8-N10-T4-E4-H7. The first complete porcine RVC genome from Russia was obtained with genomic constellation G6-P[5]-I14-R1-C1-M1-A7-N9-T6-E1-H1, and the phylogenetic analysis revealed putative novel genotype group for the VP6 gene-I14. Additionally, the first porcine kobuvirus isolate from Russia was phylogenetically characterized.</p><p><strong>Conclusions: </strong>The applied nanopore sequencing method successfully genotyped the RV isolates and additionally revealed co-circulated species. The study demonstrates high genetic variability of Russian RVA isolates in VP4/VP7 genes and phylogenetically describes local RVB and RVC. Complete characterization of genomic segments is a crucial methodology in tracing the rotavirus's evolution and evaluating interspecies transmissions.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"21 1","pages":"289"},"PeriodicalIF":4.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the MAGLUMI HIV Ab/Ag combi test for the detection of HIV infection.","authors":"Chunling Wang, Jie Rao, Zhonggang Fang, Hongwei Zhang, Jun Yin, Tinghua Li, Chen Zhang","doi":"10.1186/s12985-024-02565-x","DOIUrl":"10.1186/s12985-024-02565-x","url":null,"abstract":"<p><strong>Background: </strong>Human immunodeficiency virus (HIV) infection screening and diagnosis are critical to control the HIV epidemic. Testing for anti-HIV antibodies (Ab) and antigens (Ag) in blood samples is the first step to screen people who have been potentially exposed to the virus. This study aimed to evaluate the performance of the MAGLUMI HIV Ab/Ag Combi for detection of HIV antibodies and antigens.</p><p><strong>Methods: </strong>We used residual samples to assess the diagnostic specificity and sensitivity of the MAGLUMI HIV Ab/Ag Combi retrospectively. All samples that met the test criteria were tested with the MAGLUMI HIV Ab/Ag Combi according to manufacturer's instruction. Results of the MAGLUMI HIV Ab/Ag Combi were compared with the Architect HIV Ag/Ab Combo test.</p><p><strong>Results: </strong>The specificity of the MAGLUMI HIV Ab/Ag Combi was 99.85% in 5,057 unselected blood donors and 100.00% in 213 hospitalized patient samples, respectively. The sensitivity of the Test in 614 HIV-1 Ab, HIV-1 Ag or HIV-2 Ab positive samples was 100.00%. Seroconversion sensitivity from results of 30 panels was comparable between the MAGLUMI HIV Ab/Ag Combi and the Architect assay.</p><p><strong>Conclusions: </strong>The reactivity of the MAGLUMI HIV Ab/Ag Combi test is comparable to the Architect HIV Ag/Ab Combo assay.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"21 1","pages":"290"},"PeriodicalIF":4.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating SARS-CoV-2-related immunopathology in Crohn's disease: from molecular mechanisms to therapeutic challenges.","authors":"Chang-Cyuan Chen, Yu-An Lin, Kuan-Ting Liu, Chun-Yao Huang, Chun-Ming Shih, Yuan-Ti Lee, Jun-Liang Pan, Ai-Wei Lee","doi":"10.1186/s12985-024-02529-1","DOIUrl":"10.1186/s12985-024-02529-1","url":null,"abstract":"<p><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) not only posed major health and economic burdens to international societies but also threatens patients with comorbidities and underlying autoimmune disorders, including Crohn's disease (CD) patients. As the vaccinated population is gradually relieved from the stress of the latest omicron variant of SARS-CoV-2 due to competent immune responses, the anxiety of CD patients, especially those on immunosuppressive treatment, has not subsided. Whether the use of immunosuppressants for remission of CD outweighs the potential risk of severe coronavirus disease 2019 (COVID-19) has long been discussed. Thus, for the best benefit of CD patients, our primary goal in this study was to navigate the clinical management of CD during the COVID pandemic. Herein, we summarized COVID-19 outcomes of CD patients treated with immunosuppressive agents from multiple cohort studies and also investigated possible mechanisms of how SARS-CoV-2 impacts the host immunity with special consideration of CD patients. We first looked into the SARS-CoV-2-related immunopathology, including lymphocytopenia, T-cell exhaustion, cytokine storms, and their possible molecular interactions, and then focused on mechanistic actions of gastrointestinal systems, including interruption of tryptophan absorption, development of dysbiosis, and consequent local and systemic inflammation. Given challenges in managing CD, we summarized up-to-date clinical and molecular evidence to help physicians adjust therapeutic strategies to achieve the best clinical outcomes for CD patients.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"21 1","pages":"288"},"PeriodicalIF":4.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic epidemiology of early SARS-CoV-2 transmission dynamics in Bangladesh.","authors":"L Carnegie, J T McCrone, L du Plessis, M Hasan, M Z Ali, R Begum, M Z Hassan, S Islam, M H Rahman, A S M Uddin, M S Sarker, T Das, M Hossain, M Khan, M H Razu, A Akram, S Arina, E Hoque, M M A Molla, T Nafisaa, P Angra, A Rambaut, S T Pullan, K L Osman, M A Hoque, P Biswas, M S Flora, J Raghwani, G Fournié, M A Samad, S C Hill","doi":"10.1186/s12985-024-02560-2","DOIUrl":"10.1186/s12985-024-02560-2","url":null,"abstract":"<p><strong>Background: </strong>Genomic epidemiology has helped reconstruct the global and regional movement of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is still a lack of understanding of SARS-CoV-2 spread in some of the world's least developed countries (LDCs).</p><p><strong>Methods: </strong>To begin to address this disparity, we studied the transmission dynamics of the virus in Bangladesh during the country's first COVID-19 wave by analysing case reports and whole-genome sequences from all eight divisions of the country.</p><p><strong>Results: </strong>We detected > 50 virus introductions to the country during the period, including during a period of national lockdown. Additionally, through discrete phylogeographic analyses, we identified that geographical distance and population -density and/or -size influenced virus spatial dispersal in Bangladesh.</p><p><strong>Conclusions: </strong>Overall, this study expands our knowledge of SARS-CoV-2 genomic epidemiology in Bangladesh, shedding light on crucial transmission characteristics within the country, while also acknowledging resemblances and differences to patterns observed in other nations.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"21 1","pages":"291"},"PeriodicalIF":4.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of linear B cell epitopes on the E146L protein of African swine fever virus with monoclonal antibodies.","authors":"Shu-Jian Zhang, Bei Niu, Shi-Meng Liu, Zhi-Gao Bu, Rong-Hong Hua","doi":"10.1186/s12985-024-02570-0","DOIUrl":"10.1186/s12985-024-02570-0","url":null,"abstract":"<p><p>The outbreak and spread of African swine fever virus (ASFV) have caused considerable economic losses to the pig industry worldwide. Currently, to promote the development of effective ASF vaccines, especially subunit vaccines, more antigenic protein targets are urgently needed. In this work, six transmembrane proteins (I329L, E146L, C257L, EP153R, I177L, and F165R) were expressed in mammalian cell lines and screened with pig anti-ASFV serum. It was found that the E146L protein was an immunodominant protein antigen among the six selected proteins. Moreover, the E146L protein induced antibody responses in all immunized pigs. To gain insight into the antigenic characteristics of the E146L protein, three monoclonal antibodies (mAbs; 12H12, 15G1, and 15H10) were generated by immunizing BALB/c mice with the purified E146L protein. The epitopes of the mAbs were further finely mapped through a peptide fusion protein expression strategy. Finally, the epitopes of the mAbs were identified as ⁴⁸PDESSIAYMRFRN⁶¹ of the mAb 12H12, ¹³⁸TLTGLQRII¹⁴⁶ of the mAb 15G1, and ³⁰GWSPFKYSKGNT⁴¹ of the mAb 15H10. Furthermore, the epitope of mAb 15H10 was validated as the immunodominant epitope with ASFV-infected pig sera. The chemically synthesized mAb 15H10 epitope peptide (EP1) exhibited the most extensive immunoreactivity with artificially or naturally ASFV-infected pig sera. The epitope 15H10 is located on the surface of the E146L protein and is highly conserved. These findings provide insight into the structure and function of the E146L protein of ASFV.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"21 1","pages":"286"},"PeriodicalIF":4.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endogenous ZAP is associated with altered Zika virus infection phenotype.","authors":"Nguyen Phuong Khanh Le, Prince Pal Singh, Ahmad Jawad Sabir, Ivan Trus, Uladzimir Karniychuk","doi":"10.1186/s12985-024-02557-x","DOIUrl":"10.1186/s12985-024-02557-x","url":null,"abstract":"<p><p>The zinc finger antiviral protein 1 (ZAP) has broad antiviral activity. ZAP is an interferon (IFN)-stimulated gene, which itself may enhance type I IFN antiviral response. In a previous study, Zika virus was identified as ZAP-resistant and not sensitive to ZAP antiviral activity. Here, we found that ZAP was associated with the inhibition of Zika virus in Vero cells, in the absence of a robust type I IFN system because Vero cells are deficient for IFN-alpha and -beta. Also, quantitative RNA-seq data indicated that endogenous ZAP is associated with altered global gene expression both in the steady state and during Zika virus infection. Further studies are warranted to elucidate this IFN-alpha and -beta independent anti-Zika virus activity and involvement of ZAP.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"21 1","pages":"285"},"PeriodicalIF":4.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization and complete genome sequence of highly lytic phage active against methicillin-resistant Staphylococcus aureus (MRSA) isolated from Egypt.","authors":"Abeer K Abd El-Tawab, B A Othman, A Sharaf, Samar S El-Masry, T F El-Arabi","doi":"10.1186/s12985-024-02554-0","DOIUrl":"10.1186/s12985-024-02554-0","url":null,"abstract":"<p><strong>Background: </strong>Methicillin-Resistant Staphylococcus aureus (MRSA) is one of the most resistant bacteria to antibiotics. S. aureus is an important, widespread pathogen that can cause a variety of infectious diseases in humans and animals. Phages have been recognized as natural, safe, highly specific and effective alternatives agents to antibiotics for preventing and treating bacterial infections caused by MRSA. Therefore, this study aims at the characterization of a novel isolated lytic phage, vB_SauP_ASUmrsa123.</p><p><strong>Methods: </strong>Isolates of Staphylococcus aureus MRSA were obtained on Mannitol Salt Agar and Baird Parker Agar plates and confirmed using VITEK 2. Sewage and clinical samples were used to isolate specific phages for S. aureus MRSA, and plaque assays were used for host range determination on Luria-Bertani (LB) media. The phage morphology of the isolated phage was determined by transmission electron microscopy. The phage's whole genome sequencing was identified.</p><p><strong>Results: </strong>A total of 25 isolates of Staphylococci were obtained from different clinical sources and showed typical colonies on Baird-Parker and Mannitol Salt Agar plates. The VITEK 2 automated system revealed that all 25 isolates were confirmed as S. aureus (MRSA). Two of the most antibiotics-resistant isolates were further confirmed using 16S ribosomal RNA sequencing. A lytic phage was detected against the MRSA isolates tested In Vitro, namely vB_SauP_ASUmrsa123. The phage belonged to Rountreeviridae family based on morphological properties observed by TEM and the host range of the isolated phage was tested on the 25 clinical MRSA isolates in Vitro. The one-step growth curve of the isolated phage showed that the latent period was about 55 min, and the burst size was estimated at 167 PFU. The whole genome sequencing and annotation of genes revealed that phage vB_SauP_ASUmrsa123 contained a linear dsDNA with a size of about 17,155 bp with predicted 24 ORFs. Analysis of its genome provides valuable information approximately the variety of phages belonging to the staphylococcal phages class I.</p><p><strong>Conclusion: </strong>A lytic Podo Phage vB_SauP_ASUmrsa123 was identified against S. aureus MRSA isolates and its genome was sequenced. The phage was found to be eligible for potential application in biocontrol.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"21 1","pages":"284"},"PeriodicalIF":4.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Different immunogens and prime-boost vaccination strategies affect the efficacy of recombinant candidate vaccines against pathogenic orthopoxviruses.","authors":"Antonia Radaelli, Carlo Zanotto, Chiara Brambilla, Tommaso Adami, Francesca Paolini, Aldo Venuti, Adriana Manuka, Irsida Mehmeti, Carlo De Giuli Morghen","doi":"10.1186/s12985-024-02534-4","DOIUrl":"10.1186/s12985-024-02534-4","url":null,"abstract":"<p><p>Although not as lethal as variola virus (VARV), the cause of smallpox, monkeypox virus (MPXV) represents a threat to public health, with important infection rates and mortality in several African countries and signs of spreading worldwide. MPXV may establish new reservoirs in non-endemic countries and can be considered a possible biological weapon. Human-to-human MPXV transmission is increasing with a growing susceptibility, coincident with the declining herd immunity against smallpox. The emerging threat of MPXV highlights the urgent need for protection from new zoonotic infections, as mankind is completely unprepared for encounters with new viruses. Preventive vaccination remains the most effective control against orthopoxviruses (OPXVs) such as MPXV and prime-boost vaccination strategies can significantly influence vaccine efficacy and enhance immune responses. Our study aimed at characterizing potential vaccine candidates against OPXV infections in a murine model using DNA, viral and protein recombinant vaccines using different prime-boost regimens. The experiments employed Vaccinia virus (VACV) A33, B5, L1, and A27 envelope proteins as immunogens for both priming and boosting. Priming was carried out using a mixture of four plasmids (4pVAXmix), and boosts employed fowlpox (FWPV) recombinants (4FPmix) and/or the purified recombinant proteins (4protmix), all of them expressing the same antigens. One or two doses of the same immunogens were tested and identical protocols were also compared for intranasal (i.n.) or intramuscular (i.m.) viral administration, before challenge with the highly pathogenic VACV VV_IHD-J strain. Our results show that a single dose of any combined immunogen elicited a very low antibody response. Protein mixtures administered twice boosted the humoral response of DNA immunizations by electroporation (e. p.), but did not protect from viral challenge. The antibody neutralizing titer was inversely correlated with animals' weight loss, which was initially similar in all of the groups after the challenge, but was then reversed in mice that had been primed twice with the DNA recombinants and boosted twice with the FWPV recombinants.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"21 1","pages":"282"},"PeriodicalIF":4.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pilot-scale process development for recombinant adeno-associated virus (rAAV) production based on high-density Sf9 cell culture.","authors":"Xinran Li, Jieyi Gu, Haoquan Wu, Yuanyuan Xie","doi":"10.1186/s12985-024-02550-4","DOIUrl":"10.1186/s12985-024-02550-4","url":null,"abstract":"<p><strong>Background: </strong>In recent years, gene therapy drugs have been widely marketed, and their effectiveness and potential have been confirmed. Thus, increasing their production on an industrial scale is critical. Recombinant adeno-associated viruses (rAAVs) are optimal vectors for gene therapy applications, and the baculovirus expression vector system (BEVS), which is based on Sf9 cell culture, is a common tool for rAAV production.</p><p><strong>Methods: </strong>In this work, an Sf9 cell fed-batch process was developed using shake flasks. In the laboratory-scale bioreactor, four processes were selected as the key factors when carrying out the orthogonal experiment. On the basis of the equal P/V principle and considering the problem posed by air bubbles, a pilot-scale level bioreactor process was established.</p><p><strong>Results: </strong>Here, we describe a method in which a BEVS was used to produce rAAV vectors, with the cell density increasing to 22.8 × 10⁶ cells/mL and the rAAV titre increasing to 20 × 10¹¹ VG/mL upon adding feed material. By resolving the problems associated with high-density cell culture and air bubbles, this process was successfully scaled to a 50 L pilot-scale level.</p><p><strong>Conclusions: </strong>This successful experiment not only provides a technological basis for further scale-up but also guarantees product capacity. We hope that this development process can provide reference data for studying cell culture-based drug production.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":"21 1","pages":"281"},"PeriodicalIF":4.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}