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Liposomal nanoparticle-based conserved peptide influenza vaccine and monosodium urate crystal adjuvant elicit protective immune response in pigs

Authors Dhakal S, Cheng X, Salcido J, Renu S, Bondra K, Lakshmanappa YS, Misch C, Ghimire S, Feliciano-Ruiz N, Hogshead B, Krakowka S, Carson K, McDonough J, Lee CW, Renukaradhya GJ

Received 1 July 2018

Accepted for publication 18 August 2018

Published 24 October 2018 Volume 2018:13 Pages 6699—6715

DOI https://doi.org/10.2147/IJN.S178809

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 3

Editor who approved publication: Dr Thomas J Webster


Santosh Dhakal,1,2 Xingguo Cheng,3 John Salcido,3 Sankar Renu,1,2 Kathy Bondra,1,2 Yashavantha Shaan Lakshmanappa,1,2 Christina Misch,1,2 Shristi Ghimire,1,2 Ninoshkaly Feliciano-Ruiz,1,2 Bradley Hogshead,1,2 Steven Krakowka,4 Kenneth Carson,3 Joseph McDonough,3 Chang Won Lee,1,2 Gourapura J Renukaradhya1,2

1Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Wooster, OH 44691, USA; 2Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA; 3Pharmaceuticals and Bioengineering Department, Chemistry and Chemical Engineering Division, Southwest Research Institute, San Antonio, TX 78238-0510, USA; 4The Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA

Background: Influenza (flu) is a constant threat to humans and animals, and vaccination is one of the most effective ways to mitigate the disease. Due to incomplete protection induced by current flu vaccines, development of novel flu vaccine candidates is warranted to achieve greater efficacy against constantly evolving flu viruses.
Methods: In the present study, we used liposome nanoparticle (<200 nm diameter)-based subunit flu vaccine containing ten encapsulated highly conserved B and T cell epitope peptides to induce protective immune response against a zoonotic swine influenza A virus (SwIAV) H1N1 challenge infection in a pig model. Furthermore, we used monosodium urate (MSU) crystals as an adjuvant and co-administered the vaccine formulation as an intranasal mist to flu-free nursery pigs, twice at 3-week intervals.
Results: Liposome peptides flu vaccine delivered with MSU adjuvant improved the hemagglutination inhibition antibody titer and mucosal IgA response against the SwIAV challenge and also against two other highly genetically variant IAVs. Liposomal vaccines also enhanced the frequency of peptides and virus-specific T-helper/memory cells and IFN-γ response. The improved specific cellular and mucosal humoral immune responses in adjuvanted liposomal peptides flu vaccine partially protected pigs from flu-induced fever and pneumonic lesions, and reduced the nasal virus shedding and viral load in the lungs.
Conclusion: Overall, our study shows great promise for using liposome and MSU adjuvant-based subunit flu vaccine through the intranasal route, and provides scope for future, pre-clinical investigations in a pig model for developing potent human intranasal subunit flu vaccines.

Keywords: influenza A virus peptides, liposome nanoparticles, monosodium urate crystal adjuvant, intranasal vaccination, swine influenza virus, pigs

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