A chitosan-mediated inhalable nanovaccine against SARS-CoV-2
)
Download citation
750
Views
70
Downloads
28
Crossref
27
WoS
27
Scopus
1
CSCD
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with several antigenic variants, has grown into a global challenge, and the rapid establishment of an immune barrier is crucial to achieving long-term control of the virus. This has led to a great demand for easy preparation and scalable vaccines, especially in low-income countries. Here, we present an inhalable nanovaccine comprising chitosan and SARS-CoV-2 spike protein. The chitosan-mediated nanovaccine enabled a strong spike-specific antibody immune response and augmented local mucosal immunity in bronchoalveolar lavage and lungs, which might be capable of protecting the host from infection without systemic toxicity. In addition, the enhanced adaptive immunity stimulated by chitosan showed potential protection against SARS-CoV-2. Furthermore, inhalation of the nanovaccine induced a comparable antibody response compared to intramuscular injection. This inhalable nanovaccine against SARS-CoV-2 offers a convenient and compliant strategy to reduce the use of needles and the need for medical staff.
menu
A chitosan-mediated inhalable nanovaccine against SARS-CoV-2
)
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with several antigenic variants, has grown into a global challenge, and the rapid establishment of an immune barrier is crucial to achieving long-term control of the virus. This has led to a great demand for easy preparation and scalable vaccines, especially in low-income countries. Here, we present an inhalable nanovaccine comprising chitosan and SARS-CoV-2 spike protein. The chitosan-mediated nanovaccine enabled a strong spike-specific antibody immune response and augmented local mucosal immunity in bronchoalveolar lavage and lungs, which might be capable of protecting the host from infection without systemic toxicity. In addition, the enhanced adaptive immunity stimulated by chitosan showed potential protection against SARS-CoV-2. Furthermore, inhalation of the nanovaccine induced a comparable antibody response compared to intramuscular injection. This inhalable nanovaccine against SARS-CoV-2 offers a convenient and compliant strategy to reduce the use of needles and the need for medical staff.
References(52)
Davies, N. G.; Abbott, S.; Barnard, R. C.; Jarvis, C. I.; Kucharski, A. J.; Munday, J. D.; Pearson, C. A. B.; Russell, T. W.; Tully, D. C.; Washburne, A. D. et al. Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science 2021, 372, eabg3055.
Nonaka, C. K. V.; Franco, M. M.; Gräf, T.; de Lorenzo Barcia, C. A.; de Ávila Mendonça, R. N.; de Sousa, K. A. F.; Neiva, L. M. C.; Fosenca, V.; Mendes, A. V. A.; de Aguiar, R. S. et al. Genomic evidence of SARS-CoV-2 reinfection involving E484K spike mutation, brazil. Emerg. Infect. Dis. 2021, 27, 1522–1524.
Tegally, H.; Wilkinson, E.; Giovanetti, M.; Iranzadeh, A.; Fonseca, V.; Giandhari, J.; Doolabh, D.; Pillay, S.; San, E. J.; Msomi, N. et al. Detection of a SARS-CoV-2 variant of concern in South Africa. Nature 2021, 592, 438–443.
Liu, Y.; Liu, J. Y.; Xia, H. J.; Zhang, X. W.; Fontes-Garfias, C. R.; Swanson, K. A.; Cai, H.; Sarkar, R.; Chen, W.; Cutler, M. et al. Neutralizing activity of BNT162b2-elicited serum. N. Engl. J. Med. 2021, 384, 1466–1468.
Chen, R. E.; Zhang, X. W.; Case, J. B.; Winkler, E. S.; Liu, Y.; VanBlargan, L. A.; Liu, J. Y.; Errico, J. M.; Xie, X. P.; Suryadevara, N. et al. Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies. Nat. Med. 2021, 27, 717–726.
Wang, P. F.; Nair, M. S.; Liu, L. H.; Iketani, S.; Luo, Y.; Guo, Y. C.; Wang, M.; Yu, J.; Zhang, B. S.; Kwong, P. D. et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature 2021, 593, 130–135.
Wang, Z. J.; Schmidt, F.; Weisblum, Y.; Muecksch, F.; Barnes, C. O.; Finkin, S.; Schaefer-Babajew, D.; Cipolla, M.; Gaebler, C.; Lieberman, J. A. et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature 2021, 592, 616–622.
Letko, M.; Marzi, A.; Munster, V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat. Microbiol. 2020, 5, 562–569.
Zhou, P.; Yang, X. L.; Wang, X. G.; Hu, B.; Zhang, L.; Zhang, W.; Si, H. R.; Zhu, Y.; Li, B.; Huang, C. L. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020, 579, 270–273.
Acter, T.; Uddin, N.; Das, J.; Akhter, A.; Choudhury, T. R.; Kim, S. Evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as coronavirus disease 2019 (COVID-19) pandemic: A global health emergency. Sci. Total Environ. 2020, 730, 138996.
Li, H. J.; Wang, Y. Y.; Ji, M. Y.; Pei, F. Y.; Zhao, Q. Q.; Zhou, Y. Y.; Hong, Y. T.; Han, S. Y.; Wang, J.; Wang, Q. X. et al. Transmission routes analysis of SARS-CoV-2: A systematic review and case report. Front. Cell Dev. Biol. 2020, 8, 618.
Hassan, A. O.; Feldmann, F.; Zhao, H. Y.; Curiel, D. T.; Okumura, A.; Tang-Huau, T. L.; Case, J. B.; Meade-White, K.; Callison, J.; Chen, R. E. et al. A single intranasal dose of chimpanzee adenovirus-vectored vaccine protects against SARS-CoV-2 infection in rhesus macaques. Cell Rep. Med. 2021, 2, 100230.
Polack, F. P.; Thomas, S. J.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Perez, J. L.; Marc, G. P.; Moreira, E. D.; Zerbini, C. et al. Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine. N. Engl. J. Med. 2020, 383, 2603–2615.
Baden, L. R.; El Sahly, H. M.; Essink, B.; Kotloff, K.; Frey, S.; Novak, R.; Diemert, D.; Spector, S. A.; Rouphael, N.; Creech, C. B. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 2021, 384, 403–416.
Sadoff, J.; Le Gars, M.; Shukarev, G.; Heerwegh, D.; Truyers, C.; de Groot, A. M.; Stoop, J.; Tete, S.; Van Damme, W.; Leroux-Roels, I. et al. Interim results of a phase 1–2a trial of Ad26.COV2.S Covid-19 vaccine. N. Engl. J. Med. 2021, 384, 1824–1835.
Jin, Q. T.; Zhu, W. J.; Zhu, J. F.; Zhu, J. J.; Shen, J. J.; Liu, Z.; Yang, Y.; Chen, Q. Nanoparticle-mediated delivery of inhaled immunotherapeutics for treating lung metastasis. Adv. Mater. 2021, 33, 2007557.
Zhang, H.; Zhu, W. J.; Jin, Q. T.; Pan, F.; Zhu, J. F.; Liu, Y. B.; Chen, L. F.; Shen, J. J.; Yang, Y.; Chen, Q. et al. Inhalable nanocatchers for SARS-CoV-2 inhibition. Proc. Natl. Acad. Sci. USA 2021, 118, e2102957118.
Zheng, B.; Peng, W. C.; Guo, M. M.; Huang, M. Q.; Gu, Y. X.; Wang, T.; Ni, G. J.; Ming, D. Inhalable nanovaccine with biomimetic coronavirus structure to trigger mucosal immunity of respiratory tract against COVID-19. Chem. Eng. J. 2021, 418, 129392.
Lycke, N. Recent progress in mucosal vaccine development: Potential and limitations. Nat. Rev. Immunol. 2012, 12, 592–605.
Gerada, C.; Campbell, T. M.; Kennedy, J. J.; McSharry, B. P.; Steain, M.; Slobedman, B.; Abendroth, A. Manipulation of the innate immune response by varicella zoster virus. Front. Immunol. 2020, 11, 1.
Carroll, E. C.; Jin, L.; Mori, A.; Muñoz-Wolf, N.; Oleszycka, E.; Moran, H. B. T.; Mansouri, S.; McEntee, C. P.; Lambe, E.; Agger, E. M. et al. The vaccine adjuvant chitosan promotes cellular immunity via DNA sensor cGAS-STING-dependent induction of type i interferons. Immunity 2016, 44, 597–608.
Li, W. H.; Li, Y. M. Chemical strategies to boost cancer vaccines. Chem. Rev. 2020, 120, 11420–11478.
Wu, J. J.; Zhao, L.; Hu, H. G.; Li, W. H.; Li, Y. M. Agonists and inhibitors of the sting pathway: Potential agents for immunotherapy. Med. Res. Rev. 2020, 40, 1117–1141.
Bedford, J. G.; Caminschi, I.; Wakim, L. M. Intranasal delivery of a chitosan-hydrogel vaccine generates nasal tissue resident memory CD8+ T cells that are protective against influenza virus infection. Vaccines (Basel) 2020, 8, 572.
Tatlow, D.; Tatlow, C.; Tatlow, S.; Tatlow, S. A novel concept for treatment and vaccination against Covid-19 with an inhaled chitosan-coated DNA vaccine encoding a secreted spike protein portion. Clin. Exp. Pharmacol. Physiol. 2020, 47, 1874–1878.
Jearanaiwitayakul, T.; Seesen, M.; Chawengkirttikul, R.; Limthongkul, J.; Apichirapokey, S.; Sapsutthipas, S.; Phumiamorn, S.; Sunintaboon, P.; Ubol, S. Intranasal administration of RBD nanoparticles confers induction of mucosal and systemic immunity against SARS-CoV-2. Vaccines (Basel) 2021, 9, 768.
Zihni, C.; Mills, C.; Matter, K.; Balda, M. S. Tight junctions: From simple barriers to multifunctional molecular gates. Nat. Rev. Mol. Cell Biol. 2016, 17, 564–580.
Milewska, A.; Chi, Y.; Szczepanski, A.; Barreto-Duran, E.; Dabrowska, A.; Botwina, P.; Obloza, M.; Liu, K.; Liu, D.; Guo, X. L. et al. HTCC as a polymeric inhibitor of SARS-CoV-2 and MERS-CoV. J. Virol. 2021, 95, e01622–20.
Sharma, N.; Modak, C.; Singh, P. K.; Kumar, R.; Khatri, D.; Singh, S. B. Underscoring the immense potential of chitosan in fighting a wide spectrum of viruses: A plausible molecule against SARS-CoV-2? Int. J. Biol. Macromol. 2021, 179, 33–44.
Giurgea, L. T.; Han, A.; Memoli, M. J. Universal coronavirus vaccines: The time to start is now. npj Vaccines 2020, 5, 43–45.
Wang, J.; Chin, D.; Poon, C.; Mancino, V.; Pham, J.; Li, H.; Ho, P. Y.; Hallows, K. R.; Chung, E. J. Oral delivery of metformin by chitosan nanoparticles for polycystic kidney disease. J. Control. Release 2021, 329, 1198–1209.
Sette, A.; Crotty, S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell 2021, 184, 861–880.
Moderbacher, C R.; Ramirez, S. I.; Dan, J. M.; Grifoni, A.; Hastie, K. M.; Weiskopf, D.; Belanger, S.; Abbott, R. K.; Kim, C.; Choi, J. et al. Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity. Cell 2020, 183, 996–1012.
Cai, H.; Sun, Z. Y.; Chen, M. S.; Zhao, Y. F.; Kunz, H.; Li, Y. M. Synthetic multivalent glycopeptide-lipopeptide antitumor vaccines: Impact of the cluster effect on the killing of tumor cells. Angew. Chem., Int. Ed. 2014, 53, 1699–1703.
Wu, J. J.; Li, W. H.; Chen, P. G.; Zhang, B. D.; Hu, H. G.; Li, Q. Q.; Zhao, L.; Chen, Y. X.; Zhao, Y. F.; Li, Y. M. Targeting STING with cyclic di-GMP greatly augmented immune responses of glycopeptide cancer vaccines. Chem. Commun. 2018, 54, 9655–9658.
Wu, J. J.; Zhao, L.; Han, B. B.; Hu, H. G.; Zhang, B. D.; Li, W. H.; Chen, Y. X.; Li, Y. M. A novel STING agonist for cancer immunotherapy and a SARS-CoV-2 vaccine adjuvant. Chem. Commun. 2021, 57, 504–507.
Seregin, S. S.; Appledorn, D. M.; McBride, A. J.; Schuldt, N. J.; Aldhamen, Y. A.; Voss, T.; Wei, J. P.; Bujold, M.; Nance, W.; Godbehere, S. et al. Transient pretreatment with glucocorticoid ablates innate toxicity of systemically delivered adenoviral vectors without reducing efficacy. Mol. Ther. 2009, 17, 685–696.
Cai, H.; Huang, Z. H.; Shi, L.; Sun, Z. Y.; Zhao, Y. F.; Kunz, H.; Li, Y. M. Variation of the glycosylation pattern in MUC1 glycopeptide BSA vaccines and its influence on the immune response. Angew. Chem., Int. Ed. 2012, 51, 1719–1723.
Huang, Z. H.; Shi, L.; Ma, J. W.; Sun, Z. Y.; Cai, H.; Chen, Y. X.; Zhao, Y. F.; Li, Y. M. a totally synthetic, self-assembling, adjuvant-free MUC1 glycopeptide vaccine for cancer therapy. J. Am. Chem. Soc. 2012, 134, 8730–8733.
See, R. H.; Zakhartchouk, A. N.; Petric, M.; Lawrence, D. J.; Mok, C. P. Y.; Hogan, R. J.; Rowe, T.; Zitzow, L. A.; Karunakaran, K. P.; Hitt, M. M. et al. Comparative evaluation of two severe acute respiratory syndrome (SARS) vaccine candidates in mice challenged with SARS coronavirus. J. Gen. Virol. 2006, 87, 641–650.
Sterlin, D.; Mathian, A.; Miyara, M.; Mohr, A.; Anna, F.; Claër, L.; Quentric, P.; Fadlallah, J.; Devilliers, H.; Ghillani, P. et al. IgA dominates the early neutralizing antibody response to SARS-CoV-2. Sci. Transl. Med. 2021, 13, eabd2223.
Cervia, C.; Nilsson, J.; Zurbuchen, Y.; Valaperti, A.; Schreiner, J.; Wolfensberger, A.; Raeber, M. E.; Adamo, S.; Weigang, S.; Emmenegger, M. et al. Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19. J. Allergy Clin. Immunol. 2021, 147, 545–557.e9.
Shao, Y.; Sun, Z. Y.; Wang, Y. J.; Zhang, B. D.; Liu, D. S.; Li, Y. M. Designable immune therapeutical vaccine system based on DNA supramolecular hydrogels. ACS Appl. Mater. Interfaces 2018, 10, 9310–9314.
Grifoni, A.; Weiskopf, D.; Ramirez, S. I.; Mateus, J.; Dan, J. M.; Moderbacher, C. R.; Rawlings, S. A.; Sutherland, A.; Premkumar, L.; Jadi, R. S. et al. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell 2020, 181, 1489–1501.
Le Bert, N.; Tan, A. T.; Kunasegaran, K.; Tham, C. Y. L.; Hafezi, M.; Chia, A.; Chng, M. H. Y.; Lin, M. Y.; Tan, N.; Linster, M. et al. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature 2020, 584, 457–462.
Sekine, T.; Perez-Potti, A.; Rivera-Ballesteros, O.; Strålin, K.; Gorin, J. B.; Olsson, A.; Llewellyn-Lacey, S.; Kamal, H.; Bogdanovic, G.; Muschiol, S. et al. Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19. Cell 2020, 183, 158–168.
Pušnik, J.; Richter, E.; Schulte, B.; Dolscheid-Pommerich, R.; Bode, C.; Putensen, C.; Hartmann, G.; Alter, G.; Streeck, H. Memory B cells targeting SARS-CoV-2 spike protein and their dependence on CD4+ T cell help. Cell Rep. 2021, 35, 109320.
Yuan, Z. X.; Sun, X.; Gong, T.; Ding, H.; Fu, Y.; Zhang, Z. R. Randomly 50% N-acetylated low molecular weight chitosan as a novel renal targeting carrier. J. Drug Target. 2007, 15, 269–278.
Liu, Y.; Crowe, W. N.; Wang, L. L.; Lu, Y.; Petty, W. J.; Habib, A. A.; Zhao, D. W. An inhalable nanoparticulate STING agonist synergizes with radiotherapy to confer long-term control of lung metastases. Nat. Commun. 2019, 10, 5108.
Painter, M. M.; Mathew, D.; Goel, R. R.; Apostolidis, S. A.; Pattekar, A.; Kuthuru, O.; Baxter, A. E.; Herati, R. S.; Oldridge, D. A.; Gouma, S. et al. Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination. Immunity 2021, 54, 2133–2142.
FEEDBACK 
TOP