Elsevier

Veterinary Microbiology

Volume 250, November 2020, 108859
Veterinary Microbiology

A chimeric influenza hemagglutinin delivered by parainfluenza virus 5 vector induces broadly protective immunity against genetically divergent influenza a H1 viruses in swine

https://doi.org/10.1016/j.vetmic.2020.108859Get rights and content

Highlights

  • An HA-based vaccine candidate, created by DNA shuffling (HA-113), can be immunogenic when recombinant antigen is expressed by PIV5 (PIV5-113).

  • Immunity induced by the PIV5-113 vaccine can protect mice against infection with 4 of 5 parental HAs used to create the vaccine.

  • Immunity induced by PIV5-113 can protect pigs against infection with an influenza virus isolate that is known to be infectious in pigs.

Abstract

Pigs are an important reservoir for human influenza viruses, and influenza causes significant economic loss to the swine industry. As demonstrated during the 2009 H1N1 pandemic, control of swine influenza virus infection is a critical step toward blocking emergence of human influenza virus. An effective vaccine that can induce broadly protective immunity against heterologous influenza virus strains is critically needed. In our previous studies [McCormick et al., 2015; PLoS One, 10(6):e0127649], we used molecular breeding (DNA shuffling) strategies to increase the breadth of the variable and conserved epitopes expressed within a single influenza A virus chimeric hemagglutinin (HA) protein. Chimeric HAs were constructed using parental HAs from the 2009 pandemic virus and swine influenza viruses that had a history of zoonotic transmission to humans. In the current study, we used parainfluenza virus 5 (PIV-5) as a vector to express one of these chimeric HA antigens, HA-113. Recombinant PIV-5 expressing HA-113 (PIV5-113) were rescued, and immunogenicity and protective efficacy were tested in both mouse and pig models. The results showed that PIV5-113 can protect mice and pigs against challenge with viruses expressing parental HAs. The protective immunity was extended against other genetically diversified influenza H1-expressing viruses. Our work demonstrates that PIV5-based influenza vaccines are efficacious as vaccines for pigs. The PIV5 vaccine vector and chimeric HA-113 antigen are discussed in the context of the development of universal influenza vaccines and the potential contribution of PIV5-113 as a candidate universal vaccine.

Abbreviations

HA
hemagglutinin
PIV5
parainfluenza virus 5
PIV5-113
parainfluenza virus 5 expressing the HA from DNA expressing the HA-113 antigen
RSV
respiratory syncytial virus
MERS-CoV
Middle East Respiratory Syndrome Coronavirus
NJ76
A/New Jersey/8/1976
IA06
A/Iowa/01/2006
OH07
A/Ohio/01/2007
ME08
A/Memphis/03/2008
TN09
A/Tennessee/1-560/09
GE81
A/swine/Germany/2/1981
IA92
A/swine/Iowa/40766/1992
BR07
A/Brisbane/59/2007
CA09
A/California/4/2009
MI15
A/Michigan/45/2015
13E100
A/swine/Iowa/13E100/2013
BALF
bronchoalveolar lavage fluid
HAI
hemagglutination inhibition
ELISA
enzyme-linked immunosorbent assay
RDE
receptor-destroying enzyme
COBRA
computationally optimized broadly reactive antigen
FBS-PBST
Phosphate-buffered saline containing 10 % fetal bovine serum and 0.05 % Tween-20
IACUC
Institutional Animal Care and Use Committee
i.n.
intranasal
TCID50
50 % infectious dose in tissue culture
LD50
50 % lethal dose in mice
MDBK
Madin-Darby bovine kidney
MDCK
Madin-Darby canine kidney
MOI
multiplicity of infection
BHK
baby hamster kidney
NP
nucleoprotein
PR8
A/Puerto Rico/8/34
SH
small hydrophobic
HN
hemagglutinin-neuraminidase
ANOVA
Analysis of variance
IIV
inactivated influenza virus
LAIV
live, attenuated influenza virus

Keywords

Influenza
Universal vaccine
Interspecies transmission
Pigs
Mice

Cited by (0)

1

Current affiliation: CyanVac LLC, Athens, GA, 30602, United States.

2

Current affiliation: Department of Pediatrics, University of Pittsburgh, United States.

3

Current affiliation: Yangzhou University, Yangzhou, China.

4

Current affiliation: College of Veterinary Medicine, Department of Pathobiology, University of Illinois at Urbana-Champaign, United States.

5

Authors contributed equally to the work.

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