A self-adjuvanted nanoparticle based vaccine against infectious bronchitis virus

PLOS ONE, Sep 2018

Infectious bronchitis virus (IBV) affects poultry respiratory, renal and reproductive systems. Currently the efficacy of available live attenuated or killed vaccines against IBV has been challenged. We designed a novel IBV vaccine alternative using a highly innovative platform called Self-Assembling Protein Nanoparticle (SAPN). In this vaccine, B cell epitopes derived from the second heptad repeat (HR2) region of IBV spike proteins were repetitively presented in its native trimeric conformation. In addition, flagellin was co-displayed in the SAPN to achieve a self-adjuvanted effect. Three groups of chickens were immunized at four weeks of age with the vaccine prototype, IBV-Flagellin-SAPN, a negative-control construct Flagellin-SAPN or a buffer control. The immunized chickens were challenged with 5x104.7 EID50 IBV M41 strain. High antibody responses were detected in chickens immunized with IBV-Flagellin-SAPN. In ex vivo proliferation tests, peripheral mononuclear cells (PBMCs) derived from IBV-Flagellin-SAPN immunized chickens had a significantly higher stimulation index than that of PBMCs from chickens receiving Flagellin-SAPN. Chickens immunized with IBV-Flagellin-SAPN had a significant reduction of tracheal virus shedding and lesser tracheal lesion scores than did negative control chickens. The data demonstrated that the IBV-Flagellin-SAPN holds promise as a vaccine for IBV.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0203771&type=printable

A self-adjuvanted nanoparticle based vaccine against infectious bronchitis virus

September A self-adjuvanted nanoparticle based vaccine against infectious bronchitis virus Jianping Li 0 1 2 Zeinab H. Helal 0 1 2 Christopher P. Karch 0 2 Neha Mishra 0 1 2 Theodore Girshick 0 2 5 Antonio Garmendia 0 1 2 Peter Burkhard 0 2 3 4 Mazhar I. Khan 0 1 2 0 Current address: Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital and Harvard Medical School , Cambridge, MA , United States of America 1 Department of Pathobiology and Veterinary Science University of Connecticut , Storrs, CT , United States of America, 2 Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt, 3 The Institute of Material Sciences, University of Connecticut , Storrs, CT , United States of America 2 Editor: Paulo Lee Ho, Instituto Butantan , BRAZIL 3 Alpha-O-Peptides AG , Riehen , Switzerland 4 Department of Molecular Cell Biology, University of Connecticut , Storrs, CT , United States of America 5 Charles River Laboratories , Avian vaccine services, North Franklin, CT , United States of America Infectious bronchitis virus (IBV) affects poultry respiratory, renal and reproductive systems. Currently the efficacy of available live attenuated or killed vaccines against IBV has been challenged. We designed a novel IBV vaccine alternative using a highly innovative platform called Self-Assembling Protein Nanoparticle (SAPN). In this vaccine, B cell epitopes derived from the second heptad repeat (HR2) region of IBV spike proteins were repetitively presented in its native trimeric conformation. In addition, flagellin was co-displayed in the SAPN to achieve a self-adjuvanted effect. Three groups of chickens were immunized at four weeks of age with the vaccine prototype, IBV-Flagellin-SAPN, a negative-control construct Flagellin-SAPN or a buffer control. The immunized chickens were challenged with 5x104.7 EID50 IBV M41 strain. High antibody responses were detected in chickens immunized with IBV-Flagellin-SAPN. In ex vivo proliferation tests, peripheral mononuclear cells (PBMCs) derived from IBV-Flagellin-SAPN immunized chickens had a significantly higher stimulation index than that of PBMCs from chickens receiving Flagellin-SAPN. Chickens immunized with IBV-Flagellin-SAPN had a significant reduction of tracheal virus shedding and lesser tracheal lesion scores than did negative control chickens. The data demonstrated that the - Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: NIFA-USDA provided support for authors PB and MK and The Charles River Laboratories, Avian vaccine services, provided support in the form of salaries for authors (T.G), but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these author are articulated in the ¹author contributions‟ section. IBV-Flagellin-SAPN holds promise as a vaccine for IBV. Introduction Infectious bronchitis (IB) is a highly contagious avian disease that causes significant economic losses to the poultry industry. Commercial losses are mainly due to decreased weight gain and egg production, and a poor egg quality [ 1 ]. Infectious bronchitis virus (IBV), the causative agent of IB, belongs to the genus gamma coronavirus, and the order Nidovirales [ 2 ]. In addition to causing respiratory disease and reproductive system defects in chickens, some nephropathogenic IBV strains also affect the renal system and cause nephritis [ 3 ]. Infection with IBV is complicated when an opportunistic pathogen like E. coli is present [ 4 ]. Vaccination is utilized as a major means of controlling IB. Both live attenuated and inactivated virus vaccines are used to protect chickens against IB. However, limitations of live attenuated IBV vaccines include; reversion to virulence, tissue damage which can lead to secondary bacterial infections. In addition, the potential interference of maternal antibody on vaccine efficacy should also be taken into consideration [ 5 ]. Moreover, there is a possibility of recombination between virulent strains and vaccine strains, which may lead to the development of new pathogenic variants of IBV [6±8]. On the other hand, inactivated vaccines require priming with live attenuated vaccines, large doses of adjuvants, multiple vaccinations due to the shorter duration of the immune responses [ 9, 10 ]. These elevate the costs of vaccine production and limit its application [11]. Although DNA vaccines offer a novel method of immunization and can induce a cytotoxic T cell response, the low efficiency of these vaccines limit their application in the field [ 12 ]. Synthetic peptide vaccines alone are not immunogenic enough and require co-administration of adjuvants [ 13 ]. Therefore, there is demand for safe and more effective vaccines to control IB. Lately, there has been an increasing interest directed towards the use of nanoparticles (...truncated)


This is a preview of a remote PDF: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0203771&type=printable

Jianping Li, Zeinab H. Helal, Christopher P. Karch, Neha Mishra, Theodore Girshick, Antonio Garmendia, Peter Burkhard, Mazhar I. Khan. A self-adjuvanted nanoparticle based vaccine against infectious bronchitis virus, PLOS ONE, 2018, Volume 13, Issue 9, DOI: 10.1371/journal.pone.0203771