Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection

Kun Li; Zhuo Li; Christine Wohlford-Lenane; David K Meyerholz; Rudragouda Channappanavar; Dong An; Stanley Perlman; Paul B McCray Jr; Biao He

doi:10.1128/mBio.00554-20

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Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection

Journal article

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Peer reviewed

Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection

Kun Li, Zhuo Li, Christine Wohlford-Lenane, David K Meyerholz, Rudragouda Channappanavar, Dong An, Stanley Perlman, Paul B McCray Jr and Biao He

mBio, Vol.11(2), p.e00554-20

04/07/2020

DOI: 10.1128/mBio.00554-20

PMCID: PMC7157776

PMID: 32265331

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Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans and remains endemic in the Middle East since first being identified in 2012. There are currently no approved vaccines or therapies available for MERS-CoV. In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. A single intranasal administration of 10 PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERS 6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 10 PFU UV-inactivated MERS 6.1.2 mixed with Imject alum provided protection to only 25% of immunized mice. Intriguingly, an influx of eosinophils was observed only in the lungs of mice immunized with inactivated MERS-CoV, suggestive of a hypersensitivity-type response. Overall, our study indicated that PIV5-MERS-S is a promising effective vaccine candidate against MERS-CoV infection. MERS-CoV causes lethal infection in humans, and there is no vaccine. Our work demonstrates that PIV5 is a promising vector for developing a MERS vaccine. Furthermore, success of PIV5-based MERS vaccine can be employed to develop a vaccine for emerging CoVs such as SARS-CoV-2, which causes COVID-19.

Immunization

Coronavirus Infections - prevention & control

Spike Glycoprotein, Coronavirus - genetics

Mice, Inbred C57BL

Vaccines, Synthetic - genetics

Viral Vaccines - genetics

Parainfluenza Virus 5 - genetics

Vaccines, Synthetic - immunology

Coronavirus Infections - mortality

Administration, Intranasal

Antibodies, Viral - blood

Coronavirus Infections - immunology

Animals

Spike Glycoprotein, Coronavirus - immunology

Mice

Vaccines, Synthetic - administration & dosage

Viral Vaccines - immunology

Disease Models, Animal

Details

Title: Subtitle: Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection
Creators: Kun Li - Department of Pediatrics, Pappajohn Biomedical Institute, University of Iowa, Iowa City, Iowa, USA
Zhuo Li - Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA
Christine Wohlford-Lenane - Department of Pediatrics, Pappajohn Biomedical Institute, University of Iowa, Iowa City, Iowa, USA
David K Meyerholz - Department of Pathology, University of Iowa, Iowa City, Iowa, USA
Rudragouda Channappanavar - Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA
Dong An - Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA
Stanley Perlman - Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA
Paul B McCray Jr - Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA
Biao He - Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA paul-mccray@uiowa.edu bhe@uga.edu
Resource Type: Journal article
Publication Details: mBio, Vol.11(2), p.e00554-20
DOI: 10.1128/mBio.00554-20
PMID: 32265331
PMCID: PMC7157776
NLM abbreviation: mBio
ISSN: 2150-7511
eISSN: 2150-7511
Publisher: United States
Grant note: P01 AI060699 / NIAID NIH HHS P30 DK054759 / NIDDK NIH HHS R01 AI129269 / NIAID NIH HHS
Language: English
Date published: 04/07/2020
Academic Unit: Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Infectious Disease (Pediatrics); Internal Medicine
Record Identifier: 9984070443502771

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