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Title: Pre-clinical evaluation of a quadrivalent HCV VLP vaccine in pigs following microneedle delivery.
Austin Authors: Christiansen, D;Earnest-Silveira, L;Grubor-Bauk, B;Wijesundara, D K;Boo, I;Ramsland, Paul A ;Vincan, E;Drummer, H E;Gowans, E J;Torresi, Joseph 
Affiliation: Department of Immunology, Central Clinical School, Monash University, Melbourne, Victoria, Australia
The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia
School of Science, College of Science, Engineering and Health, RMIT University, Melbourne, Victoria, Australia
Department of Surgery, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria, Australia
Department of Surgery, The University of Adelaide and The Basil Hetzel Institute for Translational Health Research, Adelaide, South Australia, Australia
Burnet Institute, Melbourne, Victoria, Australia
Department of Microbiology, Monash University, Clayton, Australia
Issue Date: 25-Jun-2019
Date: 2019-06-25
Publication information: Scientific Reports 2019; 9(1): 9251
Abstract: The introduction of directly acting antiviral agents (DAAs) has produced significant improvements in the ability to cure chronic hepatitis C infection. However, with over 2% of the world's population infected with HCV, complications arising from the development of cirrhosis of the liver, chronic hepatitis C infection remains the leading indication for liver transplantation. Several modelling studies have indicated that DAAs alone will not be sufficient to eliminate HCV, but if combined with an effective vaccine this regimen would provide a significant advance towards achieving this critical World Health Organisation goal. We have previously generated a genotype 1a, 1b, 2a, 3a HCV virus like particle (VLP) quadrivalent vaccine. The HCV VLPs contain the core and envelope proteins (E1 and E2) of HCV and the vaccine has been shown to produce broad humoral and T cell immune responses following vaccination of mice. In this report we further advanced this work by investigating vaccine responses in a large animal model. We demonstrate that intradermal microneedle vaccination of pigs with our quadrivalent HCV VLP based vaccine produces long-lived multi-genotype specific and neutralizing antibody (NAb) responses together with strong T cell and granzyme B responses and normal Th1 and Th2 cytokine responses. These responses were achieved without the addition of adjuvant. Our study demonstrates that our vaccine is able to produce broad immune responses in a large animal that, next to primates, is the closest animal model to humans. Our results are important as they show that the vaccine can produce robust immune responses in a large animal model before progressing the vaccine to human trials.
DOI: 10.1038/s41598-019-45461-z
ORCID: 0000-0002-2107-2738
Journal: Scientific Reports
PubMed URL: 31239471
Type: Journal Article
Appears in Collections:Journal articles

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