Intranasal Administration of Novel Chitosan Nanoparticle/DNA Complexes Induces Antibody Response to Hepatitis B Surface Antigen in Mice
Abstract

The generation of strong pathogen-specific immune responses at mucosal surfaces where hepatitis B virus (HBV) transmission can occur is still a major challenge. Therefore, new vaccines are urgently needed in order to overcome the limitations of existing parenteral ones. Recent studies show that this may be achieved by intranasal immunization. Chitosan has gained attention as a nonviral gene delivery system; however, its use in vivo is limited due to low transfection efficiency mostly related to strong interaction between the negatively charged DNA and the positively charged chitosan. We hypothesize that the adsorption of negatively charged human serum albumin (HSA) onto the surface of the chitosan particles would facilitate the intracellular release of DNA, enhancing transfection activity. Here, we demonstrate that a robust systemic immune response was induced after vaccination using HSA-loaded chitosan nanoparticle/DNA (HSA-CH NP/DNA) complexes. Furthermore, intranasal immunization with HSA-CH NP/DNA complexes induced HBV specific IgA in nasal and vaginal secretions; no systemic or mucosal responses were detected after immunization with DNA alone. Overall, our results show that chitosan-based DNA complexes elicited both humoral and mucosal immune response, making them an interesting and valuable gene delivery system for nasal vaccination against HBV.
Cited By
This article is cited by 42 publications.
- Lampouguin Yenkoidiok-Douti, Christopher M. Jewell. Integrating Biomaterials and Immunology to Improve Vaccines Against Infectious Diseases. ACS Biomaterials Science & Engineering 2020, 6 (2) , 759-778. https://doi.org/10.1021/acsbiomaterials.9b01255
- Daniela Santo, Patrícia V. Mendonça, Mafalda S. Lima, Rosemeyre A. Cordeiro, Luis Cabanas, Arménio Serra, Jorge F.J. Coelho, Henrique Faneca. Poly(ethylene glycol)-block-poly(2-aminoethyl methacrylate hydrochloride)-Based Polyplexes as Serum-Tolerant Nanosystems for Enhanced Gene Delivery. Molecular Pharmaceutics 2019, 16 (5) , 2129-2141. https://doi.org/10.1021/acs.molpharmaceut.9b00101
- Daniela Santo, Rosemeyre A. Cordeiro, Ana Sousa, Arménio Serra, Jorge F.J. Coelho, and Henrique Faneca . Combination of Poly[(2-dimethylamino)ethyl methacrylate] and Poly(β-amino ester) Results in a Strong and Synergistic Transfection Activity. Biomacromolecules 2017, 18 (10) , 3331-3342. https://doi.org/10.1021/acs.biomac.7b00983
- Sara Salatin, Elham Ahmadian, Masumeh Mokhtarpour, Simin Sharifi, Aziz Eftekhari, Maleki Dizaj Solmaz, Shahriar Shahi. Introduction: An overview of the non-parenteral delivery of nanomedicine. 2021,,, 1-25. https://doi.org/10.1016/B978-0-12-820466-5.00001-6
- Nazma N. Inamdar, Vishnukant Mourya. Applications of Polymers in Delivery of Biologics. 2021,,, 449-534. https://doi.org/10.1016/B978-0-12-819659-5.00016-1
- Soojin Shim, Han Sang Yoo. The Application of Mucoadhesive Chitosan Nanoparticles in Nasal Drug Delivery. Marine Drugs 2020, 18 (12) , 605. https://doi.org/10.3390/md18120605
- Anna E. Caprifico, Elena Polycarpou, Peter J. S. Foot, Gianpiero Calabrese. Biomedical and Pharmacological Uses of Fluorescein Isothiocyanate Chitosan‐Based Nanocarriers. Macromolecular Bioscience 2020, 59 , 2000312. https://doi.org/10.1002/mabi.202000312
- Hu‐Lin Jiang, Lei Xing, Tian‐Jiao Zhou, Jia‐Hui Gong, Yu‐Jing He, Wan‐Ru Zhuang, Ki‐Hyun Cho, Chong‐Su Cho. pH‐Sensitive Modification of Chitosan as a Gene Carrier among Marine Biomaterials. 2020,,, 1249-1282. https://doi.org/10.1002/9781119143802.ch52
- Jing Zhao, Jinqi Li, Zhongliang Jiang, Rongsheng Tong, Xingmei Duan, Lan Bai, Jianyou Shi. Chitosan, N,N,N-trimethyl chitosan (TMC) and 2-hydroxypropyltrimethyl ammonium chloride chitosan (HTCC): The potential immune adjuvants and nano carriers. International Journal of Biological Macromolecules 2020, 154 , 339-348. https://doi.org/10.1016/j.ijbiomac.2020.03.065
- Sandra Jesus, Ana Patrícia Marques, Alana Duarte, Edna Soares, João Panão Costa, Mariana Colaço, Mélanie Schmutz, Claudia Som, Gerrit Borchard, Peter Wick, Olga Borges. Chitosan Nanoparticles: Shedding Light on Immunotoxicity and Hemocompatibility. Frontiers in Bioengineering and Biotechnology 2020, 8 https://doi.org/10.3389/fbioe.2020.00100
- Michael Lim, Abu Zayed Md Badruddoza, Jannatul Firdous, Mohammad Azad, Adnan Mannan, Taslim Ahmed Al-Hilal, Chong-Su Cho, Mohammad Ariful Islam. Engineered Nanodelivery Systems to Improve DNA Vaccine Technologies. Pharmaceutics 2020, 12 (1) , 30. https://doi.org/10.3390/pharmaceutics12010030
- Claudia Garnero, Virginia Aiassa, Marcela R. Longhi. Innovative technological systems to optimize the delivery and therapeutic activity of antimicrobial drugs. 2020,,, 105-139. https://doi.org/10.1016/B978-0-12-819666-3.00004-3
- Atef A. Hassan, Mogda K. Mansour, Ahmed M. El Hamaky, Rasha M. Sayed El Ahl, Noha H. Oraby. . 2020,,, 583. https://doi.org/10.1016/B978-0-12-821354-4.00024-8
- Qingliang Kong, Momoko Kitaoka, Yoshiro Tahara, Rie Wakabayashi, Noriho Kamiya, Masahiro Goto. Solid-in-oil nanodispersions for intranasal vaccination: Enhancement of mucosal and systemic immune responses. International Journal of Pharmaceutics 2019, 572 , 118777. https://doi.org/10.1016/j.ijpharm.2019.118777
- Balsam R. Rizeq, Nadin N. Younes, Kashif Rasool, Gheyath K. Nasrallah. Synthesis, Bioapplications, and Toxicity Evaluation of Chitosan-Based Nanoparticles. International Journal of Molecular Sciences 2019, 20 (22) , 5776. https://doi.org/10.3390/ijms20225776
- Filipa Lebre, Ed C. Lavelle, Olga Borges. Easy and effective method to generate endotoxin‐free chitosan particles for immunotoxicology and immunopharmacology studies. Journal of Pharmacy and Pharmacology 2019, 71 (6) , 920-928. https://doi.org/10.1111/jphp.13082
- Ye Cao, Yang Fei Tan, Yee Shan Wong, Melvin Wen Jie Liew, Subbu Venkatraman. Recent Advances in Chitosan-Based Carriers for Gene Delivery. Marine Drugs 2019, 17 (6) , 381. https://doi.org/10.3390/md17060381
- João Panão Costa, Sofia Carvalho, Sandra Jesus, Edna Soares, Ana Patrícia Marques, Olga Borges. Optimization of Chitosan-α-casein Nanoparticles for Improved Gene Delivery: Characterization, Stability, and Transfection Efficiency. AAPS PharmSciTech 2019, 20 (3) https://doi.org/10.1208/s12249-019-1342-y
- Edna Soares, Rosemeyre Cordeiro, Henrique Faneca, Olga Borges. Polymeric nanoengineered HBsAg DNA vaccine designed in combination with β‑glucan. International Journal of Biological Macromolecules 2019, 122 , 930-939. https://doi.org/10.1016/j.ijbiomac.2018.11.024
- Dulce Bento, Sandra Jesus, Filipa Lebre, Teresa Gonçalves, Olga Borges. Chitosan Plus Compound 48/80: Formulation and Preliminary Evaluation as a Hepatitis B Vaccine Adjuvant. Pharmaceutics 2019, 11 (2) , 72. https://doi.org/10.3390/pharmaceutics11020072
- Tapan Kumar Giri. Chitosan based nanoparticulate system for controlled delivery of biological macromolecules. 2019,,, 435-459. https://doi.org/10.1016/B978-0-12-816505-8.00004-7
- D.A. Diaz-Dinamarca, D.A. Soto, Y.Y. Leyton, M.J. Altamirano-Lagos, M.J. Avendaño, A.M. Kalergis, A.E. Vasquez. Oral vaccine based on a surface immunogenic protein mixed with alum promotes a decrease in Streptococcus agalactiae vaginal colonization in a mouse model. Molecular Immunology 2018, 103 , 63-70. https://doi.org/10.1016/j.molimm.2018.08.028
- Ding-Ping Bai, Xin-Yu Lin, Yi-Fan Huang, Xi-Feng Zhang. Theranostics Aspects of Various Nanoparticles in Veterinary Medicine. International Journal of Molecular Sciences 2018, 19 (11) , 3299. https://doi.org/10.3390/ijms19113299
- Edna Soares, Sandra Jesus, Olga Borges. Chitosan:β-glucan particles as a new adjuvant for the hepatitis B antigen. European Journal of Pharmaceutics and Biopharmaceutics 2018, 131 , 33-43. https://doi.org/10.1016/j.ejpb.2018.07.018
- Cristóbal Lárez Velásquez. Chitosan-based nanomaterials on controlled bioactive agents delivery: a review. Journal of Analytical & Pharmaceutical Research 2018, 7 (4) https://doi.org/10.15406/japlr.2018.07.00271
- Santosh Dhakal, Sankar Renu, Shristi Ghimire, Yashavanth Shaan Lakshmanappa, Bradley T. Hogshead, Ninoshkaly Feliciano-Ruiz, Fangjia Lu, Harm HogenEsch, Steven Krakowka, Chang Won Lee, Gourapura J. Renukaradhya. Mucosal Immunity and Protective Efficacy of Intranasal Inactivated Influenza Vaccine Is Improved by Chitosan Nanoparticle Delivery in Pigs. Frontiers in Immunology 2018, 9 https://doi.org/10.3389/fimmu.2018.00934
- Seo Jin Hong, Min Hye Ahn, Jaiprakash Sangshetti, Pill Hoon Choung, Rohidas B. Arote. Sugar-based gene delivery systems: Current knowledge and new perspectives. Carbohydrate Polymers 2018, 181 , 1180-1193. https://doi.org/10.1016/j.carbpol.2017.11.105
- Seo Jin Hong, Min Hye Ahn, Yong Woo Lee, Sukdeb Pal, Jaiprakash Sangshetti, Rohidas B. Arote. Biodegradable Polymeric Nanocarrier-Based Immunotherapy in Hepatitis Vaccination. 2018,,, 303-320. https://doi.org/10.1007/978-981-13-0950-2_16
- R. Mankamna Kumari, Nikita Sharma, Nidhi Gupta, Ramesh Chandra, Surendra Nimesh. Synthesis and evolution of polymeric nanoparticles. 2018,,, 401-438. https://doi.org/10.1016/B978-0-12-813627-0.00011-9
- Samah H. Mohamed, Abdel Satar Arafa, Wesam H. Mady, Hanan A. Fahmy, Lamiaa M. Omer, Rania E. Morsi. Preparation and immunological evaluation of inactivated avian influenza virus vaccine encapsulated in chitosan nanoparticles. Biologicals 2018, 51 , 46-53. https://doi.org/10.1016/j.biologicals.2017.10.004
- Suryani Saallah, I. Wuled Lenggoro. Nanoparticles Carrying Biological Molecules: Recent Advances and Applications. KONA Powder and Particle Journal 2018, 35 (0) , 89-111. https://doi.org/10.14356/kona.2018015
- B. Bernocchi, R. Carpentier, D. Betbeder. Nasal nanovaccines. International Journal of Pharmaceutics 2017, 530 (1-2) , 128-138. https://doi.org/10.1016/j.ijpharm.2017.07.012
- F. Lebre, D. Bento, J. Ribeiro, M. Colaço, G. Borchard, M.C. Pedroso de Lima, O. Borges. Association of chitosan and aluminium as a new adjuvant strategy for improved vaccination. International Journal of Pharmaceutics 2017, 527 (1-2) , 103-114. https://doi.org/10.1016/j.ijpharm.2017.05.028
- Lavanya Singh, Hendrik G. Kruger, Glenn E.M. Maguire, Thavendran Govender, Raveen Parboosing. The role of nanotechnology in the treatment of viral infections. Therapeutic Advances in Infectious Disease 2017, 4 (4) , 105-131. https://doi.org/10.1177/2049936117713593
- Olga Kammona, Vassilis Bourganis, Theodora Karamanidou, Costas Kiparissides. Recent developments in nanocarrier-aided mucosal vaccination. Nanomedicine 2017, 12 (9) , 1057-1074. https://doi.org/10.2217/nnm-2017-0015
- Nirmal Marasini, Mariusz Skwarczynski, Istvan Toth. Intranasal delivery of nanoparticle-based vaccines. Therapeutic Delivery 2017, 8 (3) , 151-167. https://doi.org/10.4155/tde-2016-0068
- Helmy Yusuf, Vicky Kett. Current prospects and future challenges for nasal vaccine delivery. Human Vaccines & Immunotherapeutics 2017, 13 (1) , 34-45. https://doi.org/10.1080/21645515.2016.1239668
- B. Pitard, D. Habrant. Supramolecular Gene Transfection Agents. 2017,,, 365-389. https://doi.org/10.1016/B978-0-12-409547-2.12563-6
- Motoyuki Matsuho, Riku Kubota, Shoichiro Asayama, Hiroyoshi Kawakami. Lactoferrin-modified nanoparticles loaded with potent antioxidant Mn-porphyrins exhibit enhanced antioxidative activity in vitro intranasal brain delivery model. Journal of Materials Chemistry B 2017, 5 (9) , 1765-1771. https://doi.org/10.1039/C6TB02599D
- Nattika Nantachit, Panya Sunintaboon, Sukathida Ubol. Responses of primary human nasal epithelial cells to EDIII-DENV stimulation: the first step to intranasal dengue vaccination. Virology Journal 2016, 13 (1) https://doi.org/10.1186/s12985-016-0598-z
- Eva Torres-Sangiao, Alina Holban, Monica Gestal. Advanced Nanobiomaterials: Vaccines, Diagnosis and Treatment of Infectious Diseases. Molecules 2016, 21 (7) , 867. https://doi.org/10.3390/molecules21070867
- Sai S. Sagiri, Suraj K. Nayak, S. Lakshmi, Kunal Pal. Preparation and Characterization of Biopolymeric Nanoparticles as Drug Delivery Vehicles. ,,, 225-246. https://doi.org/10.4018/978-1-5225-3023-7.ch010



