A DNA vaccine expressing consensus hemagglutinin-esterase fusion protein protected guinea pigs from infection by two lineages of influenza D virus

Yanmin Wan, Guobin Kang, Chithra Sreenivasan, Lance Daharsh, Junfeng Zhang, Wenjin Fan, Dan Wang, Hideaki Moriyama, Feng Li, Qingsheng Li

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Two lineages of influenza D virus (IDV) have been found to infect cattle and promote bovine respiratory disease complex, one of the most commonly diagnosed causes of morbidity and mortality within the cattle industry. Furthermore, IDV can infect other economically important domestic livestock, including pigs, and has the potential to infect humans, which necessitates the need for an efficacious vaccine. In this study, we designed a DNA vaccine expressing consensus hemagglutinin-esterase fusion (HEF) protein (FluD-Vax) and tested its protective efficacy against two lineages of IDV (D/OK and D/660) in guinea pigs. Animals that received FluD-Vax (n = 12) developed appreciable titers of neutralizing antibodies against IDV lineage representatives, D/OK and D/660. Importantly, vaccinated animals were protected against intranasal challenge with IDV [3 × 10 5 50% tissue culture infective dose(s) (TCID 50 )] D/OK (n = 6) or D/600 (n = 6), based on the absence of viral RNA in necropsied tissues (5 and 7 days postchallenge) using quantitative reverse transcription-PCR and in situ hybridization. In contrast, animals that received a sham DNA vaccine (n = 12) had no detectable neutralizing antibodies against IDV, and viral RNA was readily detectable in respiratory tract tissues after intranasal challenge (3 × 10 5 TCID 50 ) with IDV D/OK (n = 6) or D/660 (n = 6). Using a TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) assay, we found that IDV D/OK and D/600 infections induced apoptosis in epithelial cells lining alveoli and bronchioles, as well as nonepithelial cells in lung tissues. Our results demonstrate for the first time that the consensus IDV HEF DNA vaccine can elicit complete protection against infection from two lineages of IDV in the guinea pig model.

Original languageEnglish (US)
Article numbere00110-18
JournalJournal of virology
Volume92
Issue number11
DOIs
StatePublished - Jun 1 2018

Fingerprint

Thogotovirus
DNA Vaccines
recombinant vaccines
hemagglutinins
esterases
guinea pigs
Guinea Pigs
Infection
infection
Proteins
proteins
Gallopamil
Viral RNA
Neutralizing Antibodies
neutralizing antibodies
Bovine Respiratory Disease Complex
hemagglutinin esterase
RNA
Bronchioles
bovine respiratory disease

Keywords

  • Consensus sequence
  • DNA vaccine
  • Guinea pigs
  • Hemagglutinin-esterase-fusion protein
  • Influenza D virus

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

A DNA vaccine expressing consensus hemagglutinin-esterase fusion protein protected guinea pigs from infection by two lineages of influenza D virus. / Wan, Yanmin; Kang, Guobin; Sreenivasan, Chithra; Daharsh, Lance; Zhang, Junfeng; Fan, Wenjin; Wang, Dan; Moriyama, Hideaki; Li, Feng; Li, Qingsheng.

In: Journal of virology, Vol. 92, No. 11, e00110-18, 01.06.2018.

Research output: Contribution to journalArticle

Wan, Yanmin ; Kang, Guobin ; Sreenivasan, Chithra ; Daharsh, Lance ; Zhang, Junfeng ; Fan, Wenjin ; Wang, Dan ; Moriyama, Hideaki ; Li, Feng ; Li, Qingsheng. / A DNA vaccine expressing consensus hemagglutinin-esterase fusion protein protected guinea pigs from infection by two lineages of influenza D virus. In: Journal of virology. 2018 ; Vol. 92, No. 11.
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AU - Daharsh, Lance

AU - Zhang, Junfeng

AU - Fan, Wenjin

AU - Wang, Dan

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