Intranasal Delivery of Liposomes-Based Lipopeptide Hookworm Vaccine Diminished its Ability to Protect Mice Against Hookworm Challenge

Crossmark: check for updates

Authors

  • Stacey Bartlett School of Chemistry and Molecular Biosciences,The University of Queensland, St. Lucia, QLD 4072, Australia
  • Ramon M. Eichenberger James Cook University, Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, Cairns, Australia
  • Ahmed Shalash School of Chemistry and Molecular Biosciences,The University of Queensland, St. Lucia, QLD 4072, Australia
  • Alex Loukas James Cook University, Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, Cairns, Australia
  • Mariusz Skwarczynski School of Chemistry and Molecular Biosciences,The University of Queensland, St. Lucia, QLD 4072, Australia
  • Istvan Toth School of Chemistry and Molecular Biosciences,The University of Queensland, St. Lucia, QLD 4072, Australia; Institute of Molecular Bioscience,The University of Queensland, St. Lucia, QLD 4072, Australia; School of Pharmacy,The University of Queensland,Woolloongabba, QLD 4072, Australia
  • Waleed M. Hussein School of Chemistry and Molecular Biosciences,The University of Queensland, St. Lucia, QLD 4072, Australia

DOI:

https://doi.org/10.17140/VROJ-6-118

Keywords:

Peptide-based subunit vaccine, Hookworm, Lipopeptide, Intranasal vaccine, Nippostrongylus brasiliensis, Necator americanus

Abstract

Background
Hookworm infection is particularly problematic for middle- to low-income countries. While treatment methods are currently
available, vaccination may be the ideal intervention, as it could offer cost-effective long-term protection against infection and
reinfection.
Methods
Previously established lipopeptide-based vaccine formulations, proven to be effective in an oral application, were adapted for
an intranasal administration using a predicted B-cell peptide epitope derived from the hookworm Necator americanus aspartic
protease-1 (Na-APR-1) protein and a universal T-helper epitope attached to two lipid moieties, Pam2Cys or lipid core peptide
(LCP). The lipopeptides were encapsulated into liposomes or self-assembled into nanoparticles. The intranasal vaccine candidates
were evaluated in a rodent hookworm challenge model. .
Results
The vaccine candidates were formulated to optimal sizes and charges for uptake by immune cells. However, no significant serum
antibody response was elicited, and no protection was demonstrated following hookworm challenge.
Conclusion
In contrast to the previously reported effective oral immunization, intranasal delivery of lipopeptide-based vaccine failed to trigger
significant antibody responses in mice against hookworm and had no effect on parasite numbers following challenge infection.

References

Hotez PJ, Brooker S, Bethony JM, Bottazzi ME, Loukas A, Xiao SH. Hookworm infection. N Engl J Med. 2004; 351(8): 799-807. doi: 10.1056/NEJMra032492

Diemert DJ, Bottazzi ME, Plieskatt J, Hotez PJ, Bethony JM. Lessons along the critical path: Developing vaccines against human helminths. Trends Parasitol. 2018; 34(9): 747-758. doi: 10.1016/j. pt.2018.07.005

Pearson MS, Pickering DA, Tribolet L, Cooper L, Mulvenna J, Oliveira LM, et al. Neutralizing antibodies to the hookworm he-moglobinase Na-APR-1: Implications for a multivalent vaccine against hookworm infection and schistosomiasis. J Infect. Dis. 2010; 201(10): 1561-1569. doi: 10.1086/651953

Fuaad AAHA. Pearson MS, Pickering DA, Becker L, Zhao G, Loukas AC, et al. Lipopeptide nanoparticles: Development of vac-cines against hookworm parasite. Chem Med Chem. 2015; 10(10): 1647-1654. doi: 10.1002/cmdc.201500227

Seid CA, Curti E, Jones RM, Hudspeth E, Rezende W, Pollet J, et al. Expression, purification, and characterization of the Necator americanus aspartic protease-1 (Na-APR-1 (M74)) antigen, a com-ponent of the bivalent human hookworm vaccine. Hum Vaccin Immu-nother. 2015; 11(6): 1474-88. doi: 10.1080/21645515.2015.1036207

Bartlett S, Eichenberger RM, Nevagi RJ, Ghaffar KA, Marasini N, Dai Y, et al. Lipopeptide-based oral vaccine against hookworm infection. J Infect Dis. 2020; 221(6): 934-942. doi: 10.1093/infdis/ jiz528

Nevagi RJ, Dai W, Khalil ZG, Hussein WM, Capon RJ, Skwarc-zynski M, et al. Self-assembly of trimethyl chitosan and poly(anionic amino acid)-peptide antigen conjugate to produce a potent self-adjuvanting nanovaccine delivery system. Bioorg Med Chem. 2019; 27(14): 3082-3088. doi: 10.1016/j.bmc.2019.05.033

Tao W, Ziemer KS, Gill HS. Gold nanoparticle–M2e conjugate coformulated with CpG induces protective immunity against in-fluenza A virus. Nanomedicine (Lond). 2014; 9(2): 237-251. doi: 10.2217/nnm.13.58

Senevirathne A, Hewawaduge C, Hajam IA, Lalsiamthara J, Lee JH. Intranasally administered anti-Brucella subunit vaccine formu-lation induces protective immune responses against nasal brucella challenge. Vet Microbiol. 2019; 228: 112-118. doi: 10.1016/j.vet-mic.2018.11.022

Marasini N, Skwarczynski M, Toth I. Intranasal delivery of nanoparticle-based vaccines. Ther Deliv. 2017; 8(3): 151-167. doi: 10.4155/tde-2016-0068

Ducournau C, Moire N, Carpentier R, Cantin P, Herkt C, Lan-tier I, et al. Dimier-poisson, effective nanoparticle-based nasal vac-cine against latent and congenital toxoplasmosis in sheep. Front Im-10 Hussein WM et al munol. 2020; 11: 2183. doi: 10.3389/fimmu.2020.02183

Jackson DC, Lau YF, Le T, Suhrbier A, Deliyannis G, Cheers C, et al. A totally synthetic vaccine of generic structure that targets toll-like receptor 2 on dendritic cells and promotes antibody or cytotoxic T cell responses. Proc Natl Acad Sci USA. 2004; 101(43): 15440-15445. doi: 10.1073/pnas.0406740101

Ghosh S, Walker J, Jackson DC. Identification of canine helper T-cell epitopes from the fusion protein of canine distem-per virus. Immunology. 2001; 104(1): 58-66. doi: 10.1046/j.0019- 2805.2001.01271.x

Skwarczynski M, Zaman M, Urbani CN, Lin IC, Jia Z, Batzloff MR, et al. Polyacrylate dendrimer nanoparticles: a self-adjuvanting vaccine delivery system, Angew Chem Int Ed Engl. 2010; 49(33): 5742-5745. doi: 10.1002/anie.201002221

Ghaffar KA, Marasini N, Giddam AK, Batzloff MR, Good MF, Skwarczynski M, et al. Liposome-based intranasal delivery of lipopeptide vaccine candidates against group A streptococcus. Acta Biomater. 2016; 41: 161-168. doi: 10.1016/j.actbio.2016.04.012

Hussein WM, Liu TY, Maruthayanar P, Mukaida S, Moyle PM, Wells JW, et al. Double conjugation strategy to incorporate lipid adjuvants into multiantigenic vaccines. Chem Sci. 2016; 7(3): 2308- 2321. doi: 10.1039/C5SC03859F

Fuaad AA, Skwarczynski M, Toth I. The use of microwave-assisted solid-phase peptide synthesis and click chemistry for the synthesis of vaccine candidates against hookworm infection. Meth-ods Mol Biol. 2016; 1403; 639-653. doi: 10.1007/978-1-4939-3387- 7_36

Camberis M, Gros GL, Urban J. Animal model of nippostron-gylus brasiliensis and heligmosomoides polygyrus. Curr Protoc Im-munol. 2003; Unit 19.12. doi: 10.1002/0471142735.im1912s55

Giacomin P, Gordon D, Botto M, Daha M, Sanderson SD, Taylor S, et al. The role of complement in innate, adaptive and eosinophil-dependent immunity to the nematode nippostrongylus brasiliensis. Mol Immunol. 2008; 45(2): 446-455. doi: 10.1016/j.mo-limm.2007.05.029

Marasini N, Khalil ZG, Giddam AK, Ghaffar KA, Hussein WM, Capon RJ, et al. Lipid core peptide/poly(lactic-co-glycolic acid) as a highly potent intranasal vaccine delivery system against Group A streptococcus. Int J Pharm. 2016; 513(1-2): 410-420. doi: 10.1016/j.ijpharm.2016.09.057

Zaman M, Abdel-Aal ABM, Fujita Y, Ziora ZM, Batzloff MR, Good MF, et al. Structure-activity relationship for the development of a self-adjuvanting mucosally active lipopeptide vaccine against streptococcus pyogenes. J Med Chem. 2012; 55(19): 8515-8523. doi: 10.1021/jm301074n

Hartas J, Good MF, Batzloff MR, Jackson DC, Zeng W. Intra-Original Research | Volume 6 | Number 1| nasal vaccination with a lipopeptide containing a conformationally constrained conserved minimal peptide, a universal T cell epitope, and a self-adjuvanting lipid protects mice from group A strepto-coccus challenge and reduces throat colonization. J Infect Dis. 2006; 194(3): 325-330. doi: 10.1086/505146

Zeng W, Ghosh S, Lau YF, Brown LE, Jackson DC. Highly immunogenic and totally synthetic lipopeptides as self-adjuvanting immunocontraceptive vaccines. J Immunol. 2002; 169(9): 4905- 4912. doi: 10.4049/jimmunol.169.9.4905

Fujita Y, Abdel-Aal AE, Wimmer N, Batzloff MR, Good MF, Toth I. Synthesis and immunological evaluation of self-adjuvanting glycolipopeptide vaccine candidates. Bioorg Med Chem. 2008; 16(19): 8907-8913. doi: 10.1016/j.bmc.2008.08.064

Fuaad AAHA, Roubille R, Pearson MS, Pickering DA, Loukas AC, Skwarczynski M, et al. The use of a conformational cathepsin D-derived epitope for vaccine development against Schistosoma mansoni. Bioorg Med Chem. 2015; 23(6): 1307-1312. doi: 10.1016/j. bmc.2015.01.033

Chandrudu S, Skwarczynski M, Pattinson D, Apte SH, Doolan DL, Toth I. Synthesis and immunological evaluation of peptide-based vaccine candidates against malaria. Biochemical Compounds. 2016; 4(1): 1. doi: 10.7243/2052-9341-4-1

Skwarczynski M, Toth I. Peptide-based synthetic vaccines. Chem Sci. 2016; 7(2): 842-854. doi: 10.1039/c5sc03892h

Zhao L, Seth A, Wibowo N, Zhao CX, Mitter N, Yu C, et al. Nanoparticle vaccines. Vaccine. 2014; 32(3): 327-337. doi: 10.1016/j. vaccine.2013.11.069

Xiang SD, Scholzen A, Minigo G, David C, Apostolopoulos V, Mottram PL, et al. Pathogen recognition and development of particulate vaccines: Does size matter? Methods. 2006; 40(1): 1-9. doi: 10.1016/j.ymeth.2006.05.016

Giddam AK, Zaman M, Skwarczynski M, Toth I. Liposome-based delivery system for vaccine candidates: constructing an ef-fective formulation. Nanomedicine (Lond). 2012; 7(12): 1877-1893. doi: 10.2217/nnm.12.157

Aramaki Y, Akiyama K, Hara T, Tsuchiya S. Recognition of charged liposomes by rat peritoneal and splenic macrophages: Effects of fibronectin on the uptake of charged liposomes. Eu-ropean Journal of Pharmaceutical Sciences. 1995; 3(2): 63-70. doi: 10.1016/0928-0987(94)00075-B

A.K. Giddam, J.M. Reiman, M. Zaman, M. Skwarczynski, I. Toth, M.F. Good, A semi-synthetic whole parasite vaccine de-signed to protect against blood stage malaria. Acta Biomater. 2016; 44: 295-303. doi: 10.1016/j.actbio.2016.08.020

Khongkow M, Liu TY, Bartlett S, Hussein WM, Nevagi R, Jia ZF, et al. Liposomal formulation of polyacrylate-peptide conjugate as a new vaccine candidate against cervical cancer.. Prec Nanomed. Original Research | Volume 6 | Number 1| Hussein WM et al 2018; 1(3): 183-193. doi: 10.33218/prnano1(3).181003.1

Logan J, Pearson MS, Manda SS, Choi YJ, Field M, Eichenberg-er RM, et al. Comprehensive analysis of the secreted proteome of adult necator americanus hookworms. PLoS Negl Trop Dis. 2020; 14(5): e0008237. doi: 10.1371/journal.pntd.0008237

Sotillo J, Sanchez-Flores A, Cantacessi C, Harcus Y, Pickering D, Bouchery T, et al. Secreted proteomes of different developmen-tal stages of the gastrointestinal nematode nippostrongylus brasil-iensis. Mol Cell Proteomics. 2014; 13(10): 2736-2751. doi: 10.1074/ mcp.M114.038950

Bouchery T, Filbey K, Shepherd A, Chandler J, Patel D, Schmidt A, et al. A novel blood-feeding detoxification pathway in Nippostrongylus brasiliensis L3 reveals a potential checkpoint for arresting hookworm development. PLoS Pathog. 2018; 14(3): e1006931. doi: 10.1371/journal.ppat.1006931

Wisniewski M, Jaros S, Baska P, Cappello M, Wedrychowicz H. Ancylostoma ceylanicum metalloprotease 6 DNA vaccination induces partial protection against hookworm challenge infection. Acta Parasitol. 2013; 58(3): 376-383. doi: 10.2478/s11686-013- 0151-9

Wiśniewski M, Jaros S, Bąska P, Cappello M, Długosz E, Wędrychowicz H. Hamsters vaccinated with Ace-mep-7 DNA vaccine produced protective immunity against Ancylostoma cey-lanicum infection. Experimental Parasitology. 2016; 163: 1-7. doi: 10.1016/j.exppara.2016.01.006

Russell MW, Moldoveanu Z, Ogra PL, Mestecky J. Mucosal immunity in COVID-19: A neglected but critical aspect of SARS-CoV-2 infection. Front Immunol. 2020; 11: 611337. doi: 10.3389/ fimmu.2020.611337

Leleux J, Roy K. Micro and nanoparticle-based delivery sys-tems for vaccine immunotherapy: An immunological and materi-als perspective. Adv Healthc Mater. 2013; 2(1): 72-94. doi: 10.1002/ adhm.201200268

Nevagi RJ, Dai W, Khalil ZG, Hussein WM, Capon RJ, Skwarc-zynski M, et al. Structure-activity relationship of group A strepto-coccus lipopeptide vaccine candidates in trimethyl chitosan-based self-adjuvanting delivery system. Eur J Med Chem. 2019; 179: 100- 108. doi: 10.1016/j.ejmech.2019.06.047

Marasini N, Ghaffar KA, Giddam AK, Batzloff MR, Good MF, Skwarczynski M, et al. Highly immunogenic trimethyl chitosan-based delivery system for intranasal lipopeptide vaccines against Group A streptococcus. Curr Drug Deliv. 2017; 14(5): 701-708. doi: 10.2174/1567201813666160721141322

Marasini N, Giddam AK, Khalil ZG, Hussein WM, Capon RJ, Batzloff MR, et al. Double adjuvanting strategy for peptide-based vaccines: Trimethyl chitosan nanoparticles for lipopeptide delivery. Nanomedicine (Lond). 2016; 11: 3223-3235. doi: 10.2217/nnm-2016- 0291

Bartlett S, Skwarczynski M, Toth I. Lipids as activators of in-nate immunity in peptide vaccine delivery. Curr Med Chem. 2020; 27(17): 2887-2901. doi: 10.2174/0929867325666181026100849

Skwarczynski M, Dougall AM, Khoshnejad M, Chandrudu S, Pearson MS, Loukas A, et al. Peptide-based subunit vaccine against hookworm infection. PLoS One. 2012; 7(10): e46870. doi: 10.1371/ 12 Hussein WM et al journal.pone.0046870

Bartlett S, Eichenberger RM, Nevagi RJ, Ghaffar KA, Marasini N, Dai Y, et al. Development of natural and unnatural amino acid delivery systems against hookworm infection. Prec Nanomed. 2020; 3(1): 471-482.

Downloads

Published

2021-07-03

How to Cite

Stacey Bartlett, Ramon M. Eichenberger, Ahmed Shalash, Alex Loukas, Mariusz Skwarczynski, Istvan Toth, & Waleed M. Hussein. (2021). Intranasal Delivery of Liposomes-Based Lipopeptide Hookworm Vaccine Diminished its Ability to Protect Mice Against Hookworm Challenge. Vaccination Research, 6(1), 1–17. https://doi.org/10.17140/VROJ-6-118

Issue

Vol. 6 No. 1 (2021): Volume 6 Issue 1 2021

Section

Articles

License

Creative Commons License

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

All content published in Vaccination Research (VR) is licensed under the Creative Commons Attribution 4.0 International License (CC BY 4.0). This license allows anyone to copy, distribute, transmit, and adapt the work — including for commercial purposes — provided appropriate credit is given to the original author(s) and source.

Most read articles by the same author(s)