Using Immunoinformatics and Structural Approaches to Design a Novel HHV8 Vaccine
Tóm tắt
Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) has caused infection in different parts of the world, especially in Africa, the Middle East, and the Mediterranean. HHV8 is a gamma-2 class herpesvirus and its genome contains 26 open reading frames. K1 is a highly variable glycoprotein and can be used as a vaccine candidate. The aim of this study was to design a new vaccine by using immunoinformatics analysis and adding approved adjuvants. In this study, several computational programs were employed to define the most capable region in K1-based immunologic properties; also, different possible adjuvants and universal T-helper agonists were added to the new construct. The construct was examined to define the 3D structure, physicochemical properties and immunologic features. In addition, docking analysis was done to define the ability of the new construct to attach to mTLR. A region (155–170) was selected to be used in the new proposed vaccine; in addition, two TLR agonist adjuvants and two universal T-helpers were added to boost the immune response. Analysis of the new construct showed that the designed protein was able to be used as a vaccine and be expressed in the host. Moreover, the high energy value in docking analysis showed the high ability of this vaccine to induce immune system. The designed vaccine is expected to be capable of generating humoral and cellular responses that are crucial to protect against HHV8 as well as the vaccine has appropriate physicochemical properties and acceptable stability in different host cells.
Tài liệu tham khảo
Betsem E, Cassar O, Afonso PV, Fontanet A, Froment A, Gessain A (2014) Epidemiology and genetic variability of HHV-8/KSHV in Pygmy and Bantu populations in Cameroon. PLoS Negl Trop Dis 8:e2851
Borhani K, Bamdad T, Hashempour T (2017) Low dose of lenalidomide enhances NK cell activity: possible implication as an adjuvant. Iran J Immunol 14:151–158
Carbone A, Gloghini A, Vaccher E, Marchetti G, Gaidano G, Tirelli U (2005) KSHV/HHV-8 associated lymph node based lymphomas in HIV seronegative subjects. Report of two cases with anaplastic large cell morphology and plasmablastic immunophenotype. J Clin Pathol 58:1039–1045
Dehghani B, Rasooli I, Gargari SLM, Nadooshan MRJ, Owlia P, Nazarian S (2013) Immunogenicity of Salmonella enterica serovar Enteritidis virulence protein, InvH, and cross-reactivity of its antisera with Salmonella strains. Microbiol Res 168:84–90
Dehghani B, Rasooli I, Jalali-Nadoushan M, Owlia P, Rasooli Z (2014) Immunoprotectivity of Salmonella enterica serovar Enteritidis virulence protein, InvH, against Salmonella typhi. Iran J Basic Med Sci 17:560
Dehghani B, Ghasabi F, Hashempoor T, Joulaei H, Hasanshahi Z, Halaji M, Chatrabnous N, Mousavi Z, Moayedi J (2017) Functional and structural characterization of Ebola virus glycoprotein (1976–2015)—An in silico study. Int J Biomath 10:1750108
Duthie MS, Windish HP, Fox CB, Steven GR (2011) Use of defined TLR ligands as adjuvants within human vaccines. Immunol Rev 239:178–196
Edelman DC (2005) Human herpesvirus 8: a novel human pathogen. Virol J 2:78
Etta E, Alayande D, Mavhandu-Ramarumo L, Gachara G, Bessong P (2018) HHV-8 seroprevalence and genotype distribution in Africa, 1998–2017: a systematic review. Viruses 10:458
Farhadi T, Karimi Z, Ghasemi Y, Nezafat N, Hemmati S, Erfani N (2015) Production of a novel multi-epitope vaccine based on outer membrane proteins of Klebsiella pneumoniae. Trends Pharm Sci 1:167–172
Fraser CC, David H, Altreuter P, Ilyinskii L, Pittet RA, LaMothe M, Keegan, Johnston L, Kishimoto TK (2014) Generation of a universal CD4 memory T cell recall peptide effective in humans, mice and non-human primates. Vaccine 32:2896–2903
Giannini SL, Hanon PE, Moris M, Van Mechelen S, Morel F, Dessy MA, Fourneau B, Colau J, Suzich J, Losonksy G (2006) Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminium salt combination (AS04) compared to aluminium salt only. Vaccine 24:5937–5949
Hayashi F, Smith KD, Ozinsky A, Thomas R, Hawn CY, Goodlett DR, Eng JK, Akira S, Underhill DM, Aderem A (2001) The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410:1099
Jiang RT, Schellenbacher C, Chackerian B, Richard BSR (2016) Progress and prospects for L2-based human papillomavirus vaccines. Expert Rev Vaccines 15:853–862
Kalnin K, Tibbitts T, Stegalkina Y, Yan S, Shen L, Costa V, Sabharwal R, Anderson SF, Day PM, Christensen N (2014) Low doses of flagellin-L2 multimer vaccines protect against challenge with diverse papillomavirus genotypes. Vaccine 32:3540–3547
Kasturi SP, Skountzou I, Albrecht RA, Koutsonanos D, Hua T, Nakaya HI, Ravindran R, Stewart S, Alam M, Kwissa M (2011) Programming the magnitude and persistence of antibody responses with innate immunity. Nature 470:543
Lu J, Sun PD (2012) The structure of the TLR5-flagellin complex: a new mode of pathogen detection, conserved receptor dimerization for signaling. Sci Signal 5:pe11–pe11
Marston HD, Folkers GK, Morens DM, Anthony SF (2014) Emerging viral diseases: confronting threats with new technologies. Sci Transl Med 6:253ps10–53ps10
Masa S-R, Lando R, Sarid R (2008) Transcriptional regulation of the open reading frame 35 encoded by Kaposi’s sarcoma-associated herpesvirus. Virology 371:14–31
Mizel SB, John TB (2010) Flagellin as an adjuvant: cellular mechanisms and potential. J Immunol 185:5677–5682
Moattari A, Dehghani B, Khodadad N, Forogh, Tavakoli (2015) In silico functional and structural characterization of H1N1 influenza a viruses hemagglutinin, 2010–2013, Shiraz, Iran. Acta Biotheoretica 63:183–202
Mori J, Vranac T, Smrekar B, Černilec M, Šerbec VC, Horvat S, Ihan A, Benčina M, Jerala R (2012) Chimeric flagellin as the self-adjuvanting antigen for the activation of immune response against Helicobacter pylori, Vaccine, 30:5856–5863
Mui U, Ngoc CT, Haley R, Vangipuram, Stephen KT (2018) Human Oncoviruses: mucocutaneous manifestations, pathogenesis, therapeutics, and prevention (Part II: hepatitis viruses, human T-cell leukemia viruses, herpesviruses, and Epstein-Barr virus). J Am Acad Dermatol. https://doi.org/10.1016/j.jaad.2018.10.072
Negahdaripour M, Eslami M, Nezafat N, Hajighahramani N, Ghoshoon MB, Shoolian E, Dehshahri A, Erfani N, Morowvat MH, Ghasemi Y (2017) A novel HPV prophylactic peptide vaccine, designed by immunoinformatics and structural vaccinology approaches. Infect Genet Evol 54:402–416
Ouyang X, Zeng Y, Fu B, Wang X, Chen W, Fang Y, Luo M, Wang L (2014) Genotypic analysis of Kaposi’s sarcoma-associated herpesvirus from patients with Kaposi’s sarcoma in Xinjiang, China. Viruses 6:4800–4810
Prakash O, Swamy OR, Peng X, Tang Z-Y, Li L, Larson JE, Cohen JC, Gill J, Farr G, Wang S (2005) Activation of Src kinase Lyn by the Kaposi sarcoma-associated herpesvirus K1 protein: implications for lymphomagenesis. Blood 105:3987–9394
Pyakurel P, Pak F, Mwakigonja AR, Kaaya E, Biberfeld P (2007) KSHV/HHV-8 and HIV infection in Kaposi’s sarcoma development. Infect Agents Cancer 2:4
Ramón A, Señorale M, Marín M (2014) Inclusion bodies: not that bad… Front Microbiol 5:56
Rumbo M, Nempont C, Kraehenbuhl J-P, Jean-Claude Sirard (2006) Mucosal interplay among commensal and pathogenic bacteria: lessons from flagellin and Toll-like receptor 5. FEBS Lett 580:2976–2984
Shanmugam A, Rajoria S, George AL, Mittelman A, Suriano R, Raj KT (2012) Synthetic Toll like receptor-4 (TLR-4) agonist peptides as a novel class of adjuvants. PloS ONE 7:e30839
Song WS, Yoon S-i (2014) Crystal structure of FliC flagellin from Pseudomonas aeruginosa and its implication in TLR5 binding and formation of the flagellar filament. Biochem Biophys Res Commun 444:109–115
Song WS, Jeon YJ, Namgung B, Hong M, Yoon Sl (2017) A conserved TLR5 binding and activation hot spot on flagellin. Sci Rep 7:40878
Sra KK, Michelle Babb-Tarbox S, Aboutalebi P, Rady GL, Shipley DD, Dao, Stephen KT (2005) Molecular diagnosis of cutaneous diseases. Arch Dermatol 141:225–241
Tarahomjoo S (2014) Utilizing bacterial flagellins against infectious diseases and cancers. Antonie Van Leeuwenhoek 105:275–288
Wang L, Wakisaka N, Tomlinson CC, DeWire SM, Krall S, Pagano JS, Damania B (2004) The Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8) K1 protein induces expression of angiogenic and invasion factors. Cancer Res 64:2774–2781
Yoon S, Kurnasov O, Natarajan V, Hong M, Gudkov AV, Osterman AL, Ian AW (2012) Structural basis of TLR5-flagellin recognition and signaling. Science 335:859–864