Volume 11, Issue 3 (9-2023)                   JoMMID 2023, 11(3): 128-135 | Back to browse issues page


XML Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Hannan M, Jabalameli L, Aghasadeghi M R, Harzandi N, Sadat S M. Expression and Evaluation of a Novel HAV-VP1 and HBS-Ag Fusion Protein for Potential Applications in Immunization and Diagnosis. JoMMID 2023; 11 (3) :128-135
URL: http://jommid.pasteur.ac.ir/article-1-568-en.html
Department of Hepatitis and AIDS and Blood Borne Diseases, Pasteur Institute of Iran, Tehran, Iran
Abstract:   (958 Views)
Introduction: Hepatitis A virus (HAV) is a causative agent of acute hepatitis in humans, infecting more than one million individuals every year, including both symptomatic and asymptomatic infections. The currently available preventive vaccines for HAV are based on either wild-type or live-attenuated virus strains, which can contribute to the costliness of the vaccination process. Therefore, it may be worthwhile to explore the potential of subunit vaccines that utilize immunogenic viral products. Methods: This study presents the results of a novel recombinant protein production study that employed the native structures of HAV-VP1 and HBs-Ag. The fusion protein underwent comprehensive characterization to evaluate its potential applications in diagnostics and immunization. The truncated recombinant protein, HAV-VP1 (position 99-259 aa) -HBs-Ag, was successfully expressed in the Escherichia coli BL21-DE3 system. Results: The recombinant protein, with a molecular weight of 46 kDa, was evaluated using SDS-PAGE gel electrophoresis and confirmed by western blotting. The fusion protein was successfully detected in serum samples positive for HBV or HAV using anti-HBs and anti-VP1 antibodies. Additionally, it elicited a potent humoral response in BALB/c mice. Conclusion: The novel recombinant protein described in this study has the potential to serve as a bivalent vaccine against HAV and HBV infections. The next step involves evaluating the immunogenicity and safety profile of the protein.
Full-Text [PDF 884 kb]   (238 Downloads)    
Type of Study: Original article | Subject: Animal Models
Received: 2023/07/11 | Accepted: 2023/09/10 | Published: 2023/11/11

References
1. Castaneda D, Gonzalez AJ, Alomari M, Tandon K, Zervos XB. From hepatitis A to E: A critical review of viral hepatitis. World J Gastroenterol. 2021; 27 (16): 1691-715. [DOI:10.3748/wjg.v27.i16.1691] [PMID] [PMCID]
2. Bhadoria AS, Khwairakpam G, Grover GS, Pathak VK, Pandey P, Gupta R. Viral Hepatitis as a Public Health Concern: A Narrative Review About the Current Scenario and the Way Forward. Cureus. 2022; 14 (2): e21907-e. [DOI:10.7759/cureus.21907]
3. Larijani MS, Sadat SM, Nikbin M, Talebi SS, Javadi F, Mohajel N, et al. Correlation Study Between IL-28B Gene Polymorphism (rs8099917SNP) and Sustained Virological Response in Iranian Patients with Chronic Hepatitis C. Clinical laboratory. 2016; 62 (3): 417-23. [DOI:10.7754/Clin.Lab.2015.150724] [PMID]
4. Larijani MS, Rad LN, Nikbin M, Bahiraei N, Javadi F, Daneshvar M, et al. Impact of TGF-β1 Gene Polymorphism (rs1800469) on Treatment Response to Pegylated Interferon/Ribavirin in Iranian Patients with Hepatitis C. Clinical laboratory. 2016; 62 (4): 609-14. [DOI:10.7754/Clin.Lab.2015.150807] [PMID]
5. Larijani MS, Bahiraei N, Nikbin M, Mohajel N, Rad LN, Baghbani F, et al. Lack of TNF-α Gene Polymorphism (rs1799724) Association with Sustained Virological Response in Iranian Patients with Chronic HCV Infection. Asian Pac J Cancer Prev. 2016; 17 (8): 3923-7.
6. Armstrong GL, Bell BP. Hepatitis A virus infections in the United States: model-based estimates and implications for childhood immunization. Pediatrics. 2002; 109 (5): 839-45. [DOI:10.1542/peds.109.5.839] [PMID]
7. Chen CM, Chen SC, Yang HY, Yang ST, Wang CM. Hospitalization and mortality due to hepatitis A in Taiwan: a 15-year nationwide cohort study. J Viral Hepat. 2016; 23 (11): 940-5. [DOI:10.1111/jvh.12564] [PMID]
8. WHO position paper on hepatitis A vaccines-June 2012. Releve epidemiologique hebdomadaire. 2012; 87 (28/29): 261-76.
9. Rein DB, Stevens G, Flaxman A, Wittenborn JS, Timothy N, Wiktor SZ, et al. P703 the global burden of Hepatitis A virus in 1990 and 2005. J Hepatol. 2014; 60 (1): S303. [DOI:10.1016/S0168-8278(14)60865-5]
10. Hepatitis: Data and statistics [Internet]. 2021 [cited 2022/05/26]. Available from: https://www.euro.who.int/en/health-topics/communicable-diseases/hepatitis/data-and-statistics.
11. Scaglioni PP, Melegari M, Wands JR. Recent advances in the molecular biology of hepatitis B virus. Baillieres Clin Gastroenterol. 1996; 10 (2): 207-25. [DOI:10.1016/S0950-3528(96)90003-2] [PMID]
12. Hepatitis B [Internet]. World Health Organization. 2021 [cited 2022/05/26]. Available from: https://www.who.int/news-room/fact-sheets/detail/hepatitis-b.
13. Larijani MS, Ramezani A, Sadat SM. Updated Studies on the Development of HIV Therapeutic Vaccine. Curr HIV Res. 2019; 17 (2): 75-84. [DOI:10.2174/1570162X17666190618160608] [PMID]
14. Larijani MS, Sadat SM, Bolhassani A, Khodaie A, Pouriayevali MH, Ramezani A. HIV-1 p24-nef DNA Vaccine plus Protein Boost Expands T-Cell Responses in BALB/c. Curr Drug Deliv. 2021; 18 (7): 1014-21. [DOI:10.2174/1567201818666210101113601] [PMID]
15. Pollard AJ, Bijker EM. A guide to vaccinology: from basic principles to new developments. Nat Rev Immunol. 2021; 21 (2): 83-100. [DOI:10.1038/s41577-020-00479-7] [PMID] [PMCID]
16. Beran J. Bivalent inactivated hepatitis A and recombinant hepatitis B vaccine. Expert Rev Vaccines. 2007; 6 (6): 891-902. [DOI:10.1586/14760584.6.6.891] [PMID]
17. Herzog C, Van Herck K, Van Damme P. Hepatitis A vaccination and its immunological and epidemiological long-term effects - a review of the evidence. Hum Vaccin Immunother. 2021; 17 (5): 1496-519. [DOI:10.1080/21645515.2020.1819742] [PMID] [PMCID]
18. Hill HA, Elam-Evans LD, Yankey D, Singleton JA, Kolasa M. National, State, and Selected Local Area Vaccination Coverage Among Children Aged 19-35 Months - United States, 2014. MMWR Morb Mortal Wkly Rep. 2015; 64 (33): 889-96. [DOI:10.15585/mmwr.mm6433a1] [PMID]
19. Senger T, Schädlich L, Gissmann L, Müller M. Enhanced papillomavirus-like particle production in insect cells. Virology. 2009; 388 (2): 344-53. [DOI:10.1016/j.virol.2009.04.004] [PMID]
20. Haro I, Pinto RM, Gonzalez-Dankaart JF, Perez JA, Reig F, Bosch A. Anti-hepatitis A virus antibody response elicited in mice by different forms of a synthetic VP1 peptide. Microbiol Immunol. 1995; 39 (7): 485-90. [DOI:10.1111/j.1348-0421.1995.tb02232.x] [PMID]
21. Ping LH, Lemon SM. Antigenic structure of human hepatitis A virus defined by analysis of escape mutants selected against murine monoclonal antibodies. J Virol. 1992; 66 (4): 2208-16. [DOI:10.1128/jvi.66.4.2208-2216.1992] [PMID] [PMCID]
22. Nainan OV, Brinton MA, Margolis HS. Identification of amino acids located in the antibody binding sites of human hepatitis A virus. Virology. 1992; 191 (2): 984-7. [DOI:10.1016/0042-6822(92)90277-V] [PMID]
23. Lee JM, Lee HH, Hwang-Bo J, Shon DH, Kim W, Chung IS. Expression and immunogenicity of recombinant polypeptide VP1 of human hepatitis A virus in stably transformed fruitfly (Drosophila melanogaster) Schneider 2 cells. Biotechnol Appl Biochem. 2009; 53 (Pt 2):101-9. [DOI:10.1042/BA20080019] [PMID]
24. Chung HY, Lee HH, Kim KI, Chung HY, Hwang-Bo J, Park JH, et al. Expression of a recombinant chimeric protein of hepatitis A virus VP1-Fc using a replicating vector based on Beet curly top virus in tobacco leaves and its immunogenicity in mice. Plant Cell Rep. 2011; 30 (8): 1513-21. [DOI:10.1007/s00299-011-1062-6] [PMID]
25. Nain A, Kumar M, Banerjee M. Oligomers of hepatitis A virus (HAV) capsid protein VP1 generated in a heterologous expression system. Microb Cell Factories. 2022; 21 (1): 53. [DOI:10.1186/s12934-022-01780-x] [PMID] [PMCID]
26. Martin A, Lemon SM. Hepatitis A virus: from discovery to vaccines. Hepatology. 2006; 43 (2 Suppl 1): S164-72. [DOI:10.1002/hep.21052] [PMID]
27. Larijani MS, Sadat SM, Bolhassani A, Pouriayevali MH, Bahramali G, Ramezani A. In Silico Design and Immunologic Evaluation of HIV-1 p24-Nef Fusion Protein to Approach a Therapeutic Vaccine Candidate. Curr HIV Res. 2018; 16 (5): 322-37. [DOI:10.2174/1570162X17666190102151717] [PMID] [PMCID]
28. Larijani MS, Ramezani A, Shirazi MMA, Bolhassani A, Pouriayevali MH, Shahbazi S, et al. Evaluation of transduced dendritic cells expressing HIV-1 p24-Nef antigens in HIV-specific cytotoxic T cells induction as a therapeutic candidate vaccine. Virus Res. 2021; 298: 198403. [DOI:10.1016/j.virusres.2021.198403] [PMID]
29. Sambrook J RD. Molecular cloning. 3 rd edition. New York: CSHL press; 2001.
30. Migueres M, Lhomme S, Izopet J. Hepatitis A: Epidemiology, High-Risk Groups, Prevention and Research on Antiviral Treatment. Viruses. 2021; 13 (10): 1900. [DOI:10.3390/v13101900] [PMID] [PMCID]
31. Wang M, Feng Z. Mechanisms of Hepatocellular Injury in Hepatitis A. Viruses. 2021; 13 (5): 861. [DOI:10.3390/v13050861] [PMID] [PMCID]
32. Verma R, Khanna P. Hepatitis A vaccine should receive priority in National Immunization Schedule in India. Hum Vaccin Immunother. 2012; 8 (8): 1132-4. [DOI:10.4161/hv.20475] [PMID] [PMCID]
33. Lemon SM, Ott JJ, Van Damme P, Shouval D. Type A viral hepatitis: A summary and update on the molecular virology, epidemiology, pathogenesis and prevention. J Hepatol. 2017; S0168-8278 (17) 32278-X.
34. Stuurman AL, Marano C, Bunge EM, De Moerlooze L, Shouval D. Impact of universal mass vaccination with monovalent inactivated hepatitis A vaccines - A systematic review. Hum Vaccin Immunother. 2017; 13 (3): 724-36. [DOI:10.1080/21645515.2016.1242539] [PMID] [PMCID]
35. Larijani MS, Pouriayevali MH, Sadat SM, Ramezani A. Production of Recombinant HIV-1 p24-Nef Protein in Two Forms as Potential Candidate Vaccines in Three Vehicles. Curr Drug Deliv. 2020; 17 (5): 387-95. [DOI:10.2174/1567201817666200317121728] [PMID]
36. Ai J, Zhang H, Zhang Q, Zhang Y, Lin K, Fu Z, et al. Recombinant protein subunit vaccine booster following two-dose inactivated vaccines dramatically enhanced anti-RBD responses and neutralizing titers against SARS-CoV-2 and Variants of Concern. Cell Res. 2022; 32 (1): 103-6. [DOI:10.1038/s41422-021-00590-x] [PMID] [PMCID]
37. Khudyakov YE, Lopareva EN, Jue DL, Fang S, Spelbring J, Krawczynski K, et al. Antigenic epitopes of the hepatitis A virus polyprotein. Virology. 1999; 260 (2): 260-72. [DOI:10.1006/viro.1999.9813] [PMID]
38. da Silva Junior HC, da Silva ED, Lewis-Ximenez de Souza Rodrigues LL, Medeiros MA. Recombinant VP1 protein as a potential marker for the diagnosis of acute hepatitis A virus infection. J Virol Methods. 2017; 245: 1-4. [DOI:10.1016/j.jviromet.2017.03.005] [PMID]
39. Jang KO, Park JH, Lee HH, Chung DK, Kim W, Chung IS. Expression and immunogenic analysis of recombinant polypeptides derived from capsid protein VP1 for developing subunit vaccine material against hepatitis A virus. Protein Expr Purif. 2014; 100: 1-9. [DOI:10.1016/j.pep.2014.04.011] [PMID]

Add your comments about this article : Your username or Email:
CAPTCHA

Send email to the article author


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.