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J Virol. 2018 Mar 7. pii: JVI.00110-18. doi: 10.1128/JVI.00110-18. [Epub ahead of print]
A DNA vaccine expressing consensus hemagglutinin-esterase fusion protein protected guinea pigs from infection by two lineages of influenza D virus.
Wan Y1,1, Kang G1,1, Sreenivasan C2, Daharsh L1,1, Zhang J1,1, Fan W1,1, Wang D2, Moriyama H1, Li F2, Li Q3,1.
Author information
Abstract
Two lineages of Influenza D virus (IDV) have been found to infect cattle and promote bovine respiratory disease complex (BRDC), 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 (3E5 TCID50) D/OK (n=6) or D/600 (n=6) based on the absence of viral RNA in necropsied tissues (5 and 7 days post challenge) using qRT-PCR and in situ hybridization (ISH). 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 with IDV (3E5 TCID50) D/OK (n=6) or D/660 (n=6). Using a TUNEL assay, we found that IDV D/OK and D/600 infections induced apoptosis in epithelial cells lining alveoli and bronchioles as well as non-epithelial cells in lung tissues. Our results have demonstrated 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.IMPORTANCE IDV infection has been associated with BRDC, one of the most devastating diseases of the cattle population. Moreover, with broad host range and high environmental stability, IDV has the potential to further gain virulence, or even infect humans. An efficacious vaccine is needed to prevent infection and stop potential cross-species transmission. In this study, we designed a DNA vaccine encoding the consensus HEF of two lineages of IDV (D/OK and D/660) and tested its efficacy in a guinea pig model. Our results showed that the consensus DNA vaccine elicited high-titer neutralizing antibodies and achieved sterilizing protection against two lineage-representative IDV intra-nasal infections. To our knowledge, this is the first study showing a DNA vaccine-expressing consensus HEF is efficacious in preventing different lineages of influenza D virus infections.
PMID: 29514906 DOI: 10.1128/JVI.00110-18
A DNA vaccine expressing consensus hemagglutinin-esterase fusion protein protected guinea pigs from infection by two lineages of influenza D virus.
Wan Y1,1, Kang G1,1, Sreenivasan C2, Daharsh L1,1, Zhang J1,1, Fan W1,1, Wang D2, Moriyama H1, Li F2, Li Q3,1.
Author information
Abstract
Two lineages of Influenza D virus (IDV) have been found to infect cattle and promote bovine respiratory disease complex (BRDC), 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 (3E5 TCID50) D/OK (n=6) or D/600 (n=6) based on the absence of viral RNA in necropsied tissues (5 and 7 days post challenge) using qRT-PCR and in situ hybridization (ISH). 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 with IDV (3E5 TCID50) D/OK (n=6) or D/660 (n=6). Using a TUNEL assay, we found that IDV D/OK and D/600 infections induced apoptosis in epithelial cells lining alveoli and bronchioles as well as non-epithelial cells in lung tissues. Our results have demonstrated 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.IMPORTANCE IDV infection has been associated with BRDC, one of the most devastating diseases of the cattle population. Moreover, with broad host range and high environmental stability, IDV has the potential to further gain virulence, or even infect humans. An efficacious vaccine is needed to prevent infection and stop potential cross-species transmission. In this study, we designed a DNA vaccine encoding the consensus HEF of two lineages of IDV (D/OK and D/660) and tested its efficacy in a guinea pig model. Our results showed that the consensus DNA vaccine elicited high-titer neutralizing antibodies and achieved sterilizing protection against two lineage-representative IDV intra-nasal infections. To our knowledge, this is the first study showing a DNA vaccine-expressing consensus HEF is efficacious in preventing different lineages of influenza D virus infections.
PMID: 29514906 DOI: 10.1128/JVI.00110-18