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
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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)