Polymer-basednanoadjuvants for hepatitis C vaccine: The perspectives of immunologists

Document Type: Review Paper

Authors

1 Visiting Professor, Department of Biotechnology, University of Verona, Veneto, Italy

2 Faculty of Medical Technology, Western University, Kanchanaburi, Thailand, 71170

10.22038/nmj.2020.07.002

Abstract

The hepatitis C virus (HCV) is an infection that affects the liver tissues in humans, leading to the development of effective prophylactic and therapeutic HCV vaccines to prevent a global epidemic. Scientists consider it challenging to produce a therapeutic vaccine for the treatment of hepatocellular carcinoma as opposed to a preventative vaccine. However, several drawbacks are involved with a peptide vaccine, including the low immunogenicity of the protein, significant instability, difficulty in delivery, and inefficient presentation of the antigens. Therefore, the investigation of adjuvants (i.e., immunomodulators) to enhance the efficacy of the vaccine is essential. Nanoparticles could potentially serve as vaccine delivery vehicles, acting as adjuvants for the effective transfer of antigens. The safety and effectiveness of nanoparticles and liposomes in modern vaccinology have also been confirmed. Biodegradable nanopolymers such as polyesters, polylactic acid and the copolymers, polyorthoesters, polyanhydrides, and polycarbonates are commonly used owing to their proper qualities in the combination or loading for the prevention of the degradation of the delivered antigens. The present study is specifically focused on the polymer-based nanoparticles that are mostly comprised a poly (amino acid) based copolymer and poly (D, L-lactic-co-glycolide), which could act as adjuvants or potential immunomodulators for the systems providing effective HCV vaccine delivery.

Keywords


1.Guobuzaite A, Chokshi S, Balciuniene L, Voinic A, Stikleryte A, Zagminas K. Viral clearance or persistence after acute hepatitis C infection: interim results from a prospective study. Medicina (Kaunas). 2008; 44(7):510-520.
2.Khan S, Rai MA, Khan A, Farooqui A, Kazmi SU, Ali SH. Prevalence of HCV and HIV infections in 2005-Earthquake-affected areas of Pakistan. BMC Infect Dis. 2008; 8: 147.
3.El-Hazmi MM. Prevalence of HBV, HCV, HIV-1, 2 and HTLV-I/II infections among blood donors in a teaching hospital in the Central region of Saudi Arabia. Saudi Med J. 2004; 25(1): 26-33.
4.Arichi T, Saito T, Major ME, Belyakov IM, Shirai M, Engelhard VH. Prophylactic DNA vaccine for hepatitis C virus (HCV) infection: HCV-specific cytotoxic T lymphocyte induction and protection from HCV-recombinant vaccinia infection in an HLA-A2.1 transgenic mouse model. Proc Natl Acad Sci U S A. 2000; 97(1): 297-302.
5.Op De Beeck A, Cocquerel L, Dubuisson J. Biogenesis of hepatitis C virus envelope glycoproteins. J Gen Virol. 2001; 82(Pt 11): 2589-2595.
6.Kapadia SB, Chisari FV. Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids. Proc Natl Acad Sci U S A. 2005; 102(7): 2561-2566.
7.Moradpour D, Brass V, Gosert R, Wolk B, Blum HE. Hepatitis C: molecular virology and antiviral targets. Trends Mol Med. 2002; 8(10): 476-482.
8.Calvo Manuel E, Nieto Sanchez A, Espinos Perez D. [Interferon treatment in chronic HCV hepatitis and autoimmune hypothyroidism]. An Med Interna. 2000; 17(3): 164-165.
9.Hoofnagle JH, Seeff LB. Peginterferon and ribavirin for chronic hepatitis C. N Engl J Med. 2006; 355(23): 2444-2451.
10.Kallinowski B, Liehr H, Moeller B, Stremmel W, Wechsler JG, Wiese M. Combination therapy with interferon-alpha 2b and ribavirin for the treatment of relapse patients and non-responders with chronic HCV infection. Z Gastroenterol. 2001; 39(3): 199-204, 6.
11.Iino S, Tomita E, Kumada H, Suzuki H, Toyota J, Kiyosawa K. Prediction of treatment outcome with daily high-dose IFN alpha-2b plus ribavirin in patients with chronic hepatitis C with genotype 1b and high HCV RNA levels: relationship of baseline viral levels and viral dynamics during and after therapy. Hepatol Res. 2004; 30(2): 63-70.
12.Laguno M, Murillas J, Blanco JL, Martinez E, Miquel R, Sanchez-Tapias JM, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for treatment of HIV/HCV co-infected patients. AIDS. 2004;18(13):F27-36.
13.Allard L, Cheynet V, Oriol G, Gervasi G, Imbert-Laurenceau E, Mandrand B. Antigenicity of recombinant proteins after regioselective immobilization onto polyanhydride-based copolymers. Bioconjug Chem. 2004;15(3): 458-466.
14.Xie Y, Xu DZ, Lu ZM, Luo KX, Jia JD, Wang YM, et al. [The influence of HCV genotype on the IFN treatment of patients with chronic hepatitis C]. Zhonghua Gan Zang Bing Za Zhi. 2004; 12(2): 72-75.
15.Idrees S, Ashfaq UA, Idrees N. Development of global consensus sequence of HCV glycoproteins involved in viral entry. Theor Biol Med Model. 2013; 10: 24.
16.Bartosch B, Dubuisson J, Cosset FL. Infectious hepatitis C virus pseudo-particles containing functional E1-E2 envelope protein complexes. J Exp Med. 2003; 197(5): 633-642.
17.Nielsen SU, Bassendine MF, Burt AD, Bevitt DJ, Toms GL. Characterization of the genome and structural proteins of hepatitis C virus resolved from infected human liver. J Gen Virol. 2004; 85(Pt 6): 1497-1507.
18.Weiner AJ, Christopherson C, Hall JE, Bonino F, Saracco G, Brunetto MR, et al. Sequence variation in hepatitis C viral isolates. J Hepatol. 1991; 13 Suppl 4: S6-14.
19.Ashfaq UA, Qasim M, Yousaf MZ, Awan MT, Jahan S. Inhibition of HCV 3a genotype entry through host CD81 and HCV E2 antibodies. J Transl Med. 2011; 9: 194.
20.Flint M, McKeating JA. The role of the hepatitis C virus glycoproteins in infection. Rev Med Virol. 2000; 10(2): 101-117.
21.Scarselli E, Ansuini H, Cerino R, Roccasecca RM, Acali S, Filocamo G. The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J. 2002; 21(19): 5017-5025.
22.Gardner JP, Durso RJ, Arrigale RR, Donovan GP, Maddon PJ, Dragic T. L-SIGN (CD 209L) is a liver-specific capture receptor for hepatitis C virus. Proc Natl Acad Sci U S A. 2003; 100(8): 4498-4503.
23.Helle F, Dubuisson J. Hepatitis C virus entry into host cells. Cell Mol Life Sci. 2008; 65(1): 100-112.
24.Monazahian M, Bohme I, Bonk S, Koch A, Scholz C, Grethe S. Low density lipoprotein receptor as a candidate receptor for hepatitis C virus. J Med Virol. 1999; 57(3): 223-229.
25.Liu J, Zhu L, Zhang X, Lu M, Kong Y, Wang Y. Expression, purification, immunological characterization and application of Escherichia coli-derived hepatitis C virus E2 proteins. Biotechnol Appl Biochem. 2001; 34(Pt 2): 109-119.
26.Feinstone SM, Hu DJ, Major ME. Prospects for prophylactic and therapeutic vaccines against hepatitis C virus. Clin Infect Dis. 55 Suppl 1: S25-32.
27.Hung CF, Ma B, Monie A, Tsen SW, Wu TC. Therapeutic human papillomavirus vaccines: current clinical trials and future directions. Expert Opin Biol Ther. 2008; 8(4): 421-439.
28.Le Corre P, Rytting JH, Gajan V, Chevanne F, Le Verge R. In vitro controlled release kinetics of local anaesthetics from poly(D,L-lactide) and poly(lactide-co-glycolide) microspheres. J Microencapsul. 1997; 14(2): 243-255.
29.Vogel FR. Improving vaccine performance with adjuvants. Clin Infect Dis. 2000; 30 Suppl 3: S266-70.
30.Wu JY, Gardner BH, Kushner NN, Pozzi LA, Kensil CR, Cloutier PA, et al. Accessory cell requirements for saponin adjuvant-induced class I MHC antigen-restricted cytotoxic T-lymphocytes. Cell Immunol. 1994; 154(1): 393-406.
31.Dupuis M, Murphy TJ, Higgins D, Ugozzoli M, van Nest G, Ott G. Dendritic cells internalize vaccine adjuvant after intramuscular injection. Cell Immunol. 1998; 186(1): 18-27.
32.Kovacsovics-Bankowski M, Rock KL. A phagosome-to-cytosol pathway for exogenous antigens presented on MHC class I molecules. Science. 1995; 267(5195): 243-246.
33.Zhou F, Huang L. Liposome-mediated cytoplasmic delivery of proteins: an effective means of accessing the MHC class I-restricted antigen presentation pathway. Immunomethods. 1994; 4(3): 229-235.
34.Audibert FM, Lise LD. Adjuvants: current status, clinical perspectives and future prospects. Immunol Today. 1993; 14(6): 281-284.
35.Unkeless JC, Scigliano E, Freedman VH. Structure and function of human and murine receptors for IgG. Annu Rev Immunol. 1988; 6: 251-281.
36.Phillips NC, Emili A. Enhanced antibody response to liposome-associated protein antigens: preferential stimulation of IgG2a/b production. Vaccine. 1992; 10(3): 151-158.
37.Pardoll DM. Paracrine cytokine adjuvants in cancer immunotherapy. Annu Rev Immunol. 1995; 13: 399-415.
38.Jankovic D, Caspar P, Zweig M, Garcia-Moll M, Showalter SD, Vogel FR. Adsorption to aluminum hydroxide promotes the activity of IL-12 as an adjuvant for antibody as well as type 1 cytokine responses to HIV-1 gp120. J Immunol. 1997; 159(5): 2409-2417.
39.Holmgren J, Lycke N, Czerkinsky C. Cholera toxin and cholera B subunit as oral-mucosal adjuvant and antigen vector systems. Vaccine. 1993; 11(12): 1179-1184.
40.Xu-Amano J, Kiyono H, Jackson RJ, Staats HF, Fujihashi K, Burrows PD. Helper T cell subsets for immunoglobulin A responses: oral immunization with tetanus toxoid and cholera toxin as adjuvant selectively induces Th2 cells in mucosa associated tissues. J Exp Med. 1993; 178(4): 1309-1320.
41.Wilson AD, Robinson A, Irons L, Stokes CR. Adjuvant action of cholera toxin and pertussis toxin in the induction of IgA antibody response to orally administered antigen. Vaccine. 1993; 11(2): 113-118.
42.Lindsay DS, Parton R, Wardlaw AC. Adjuvant effect of pertussis toxin on the production of anti-ovalbumin IgE in mice and lack of direct correlation between PCA and ELISA. Int Arch Allergy Immunol. 1994; 105(3): 281-288.
43.Oyewumi MO, Kumar A, Cui Z. Nano-microparticles as immune adjuvants: correlating particle sizes and the resultant immune responses. Expert Rev Vaccines. 9(9): 1095-1107.
44.Ferreira SA, Gama FM, Vilanova M. Polymeric nanogels as vaccine delivery systems. Nanomedicine. 2013; 9(2): 159-173.
45.De Geest BG, Willart MA, Hammad H, Lambrecht BN, Pollard C, Bogaert P. Polymeric multilayer capsule-mediated vaccination induces protective immunity against cancer and viral infection. ACS Nano. 2012; 6(3): 2136-2149.
46.Zhuang Y, Ma Y, Wang C, Hai L, Yan C, Zhang Y. PEGylated cationic liposomes robustly augment vaccine-induced immune responses: Role of lymphatic trafficking and biodistribution. J Control Release. 2012; 159(1): 135-142.
47.Reddy ST, Swartz MA, Hubbell JA. Targeting dendritic cells with biomaterials: developing the next generation of vaccines. Trends Immunol. 2006; 27(12): 573-579.
48.Bobardt MD, Cheng G, de Witte L, Selvarajah S, Chatterji U, Sanders-Beer BE. Hepatitis C virus NS5A anchor peptide disrupts human immunodeficiency virus. Proc Natl Acad Sci U S A. 2008; 105(14): 5525-5530.
49.Cheng G, Montero A, Gastaminza P, Whitten-Bauer C, Wieland SF, Isogawa M. A virocidal amphipathic {alpha}-helical peptide that inhibits hepatitis C virus infection in vitro. Proc Natl Acad Sci U S A. 2008; 105(8): 3088-3093.
50.Zhang J, Mulvenon A, Makarov E, Wagoner J, Knibbe J, Kim JO. Antiviral peptide nanocomplexes as a potential therapeutic modality for HIV/HCV co-infection. Biomaterials. 2013; 34(15): 3846-3857.
51.Zhang J, Garrison JC, Poluektova LY, Bronich TK, Osna NA. Liver-targeted antiviral peptide nanocomplexes as potential anti-HCV therapeutics. Biomaterials. 2015; 70: 37-47.
52.Katare YK, Panda AK. Immunogenicity and lower dose requirement of polymer entrapped tetanus toxoid co-administered with alum. Vaccine. 2006; 24(17): 3599-3608.
53.Diwan M, Elamanchili P, Cao M, Samuel J. Dose sparing of CpG oligodeoxynucleotide vaccine adjuvants by nanoparticle delivery. Curr Drug Deliv. 2004; 1(4): 405-412.
54.Hamdy S, Haddadi A, Hung RW, Lavasanifar A. Targeting dendritic cells with nano-particulate PLGA cancer vaccine formulations. Adv Drug Deliv Rev. 63(10-11): 943-955.
55.Kovacsovics-Bankowski M, Clark K, Benacerraf B, Rock KL. Efficient major histocompatibility complex class I presentation of exogenous antigen upon phagocytosis by macrophages. Proc Natl Acad Sci U S A. 1993; 90(11): 4942-4946.
56.Cruz LJ, Tacken PJ, Fokkink R, Joosten B, Stuart MC, Albericio F. Targeted PLGA nano- but not microparticles specifically deliver antigen to human dendritic cells via DC-SIGN in vitro. J Control Release. 2010; 144(2): 118-126.
57.Panyam J, Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev. 2003; 55(3): 329-347.
58.Sarti F, Perera G, Hintzen F, Kotti K, Karageorgiou V, Kammona O. In vivo evidence of oral vaccination with PLGA nanoparticles containing the immunostimulant monophosphoryl lipid A. Biomaterials. 2011; 32(16): 4052-4057.
59.Jeon HJ, Jeong YI, Jang MK, Park YH, Nah JW. Effect of solvent on the preparation of surfactant-free poly(DL-lactide-co-glycolide) nanoparticles and norfloxacin release characteristics. Int J Pharm. 2000; 207(1-2): 99-108.
60.Shen H, Ackerman AL, Cody V, Giodini A, Hinson ER, Cresswell P. Enhanced and prolonged cross-presentation following endosomal escape of exogenous antigens encapsulated in biodegradable nanoparticles. Immunology. 2006; 117(1): 78-88.
61.Sharma C, Khan MA, Mohan T, Shrinet J, Latha N, Singh N. A synthetic chimeric peptide harboring human papillomavirus 16 cytotoxic T lymphocyte epitopes shows therapeutic potential in a murine model of cervical cancer. Immunol Res.58(1): 132-138.
62.Roopngam P, Liu K, Mei L, Zheng Y, Zhu X, Tsai HI. Hepatitis C virus E2 protein encapsulation into poly d, l-lactic-co-glycolide microspheres could induce mice cytotoxic T-cell response. Int J Nanomedicine. 2016; 11: 5361-5370.
63.Alonso MJ, Gupta RK, Min C, Siber GR, Langer R. Biodegradable microspheres as controlled-release tetanus toxoid delivery systems. Vaccine. 1994; 12(4): 299-306.
64.Boehm U, Klamp T, Groot M, Howard JC. Cellular responses to interferon-gamma. Annu Rev Immunol. 1997; 15: 749-795.
65.Whitmire JK, Tan JT, Whitton JL. Interferon-gamma acts directly on CD8+ T cells to increase their abundance during virus infection. J Exp Med. 2005; 201(7): 1053-1059.
66.Mocikat R, Braumuller H, Gumy A, Egeter O, Ziegler H, Reusch U. Natural killer cells activated by MHC class I(low) targets prime dendritic cells to induce protective CD8 T cell responses. Immunity. 2003; 19(4): 561-569.
67.Abd Ellah NH, Tawfeek HM, John J, Hetta HF. Nanomedicine as a future therapeutic approach for Hepatitis C virus. Nanomedicine (Lond). 2019; 14(11): 1471-1491.
68.Hekmat S, Siadat SD, Aghasadeghi MR, Sadat SM, Bahramali G, Aslani MM, et al. From in-silico immunogenicity verification to in vitro expression of recombinant Core-NS3 fusion protein of HCV. Bratislavske lekarske listy. 2017; 118(4): 189-195.
69.Sabet S, George MA, El-Shorbagy HM, Bassiony H, Farroh KY, Youssef T, et al. Gelatin nanoparticles enhance delivery of hepatitis C virus recombinant NS2 gene. PLoS One. 2017; 12(7): e0181723.
70.Lee H, Jeong JH, Park TG. PEG grafted polylysine with fusogenic peptide for gene delivery: high transfection efficiency with low cytotoxicity. J Control Release. 2002; 79(1-3): 283-2891.
71.Yang Y, Kuang Y, Liu Y, Li W, Jiang Z, Xiao L, et al. Immunogenicity of multiple-epitope antigen gene of HCV carried by novel biodegradable polymers. Comparative immunology, microbiology and infectious diseases. 2011; 34(1): 65-72.
72.Sepulveda-Crespo D, Jimenez JL, Gomez R, De La Mata FJ, Majano PL, Munoz-Fernandez MA. Polyanionic carbosilane dendrimers prevent hepatitis C virus infection in cell culture. Nanomedicine. 2017; 13(1): 49-58.