Abstract
Since December 2014, Eurasian-origin, highly pathogenic avian influenza H5 viruses including H5N1, H5N2, and H5N8 subtypes (called H5Nx viruses), which belong to the H5 clade 2.3.4.4, have been detected in U.S. wild birds. Subsequently, highly pathogenic H5N2 and H5N8 viruses have caused outbreaks in U.S. domestic poultry. Vaccination is one of the most effective ways to control influenza outbreaks and protect animal and public health. Newcastle disease virus (NDV)-based influenza vaccines have been demonstrated to be efficacious and safe in poultry. Herein, we developed an NDV-based H5 vaccine (NDV-H5) that expresses a codon-optimized ectodomain of the hemagglutinin from the A/chicken/Iowa/04-20/2015 (H5N2) virus and evaluated its efficacy in chickens. Results showed that both live and inactivated NDV-H5 vaccines induced hemagglutinin inhibition antibody titers against the H5N2 virus in immunized chickens after prime and booster, and both NDV-H5 vaccines completely protected chickens from lethal challenge with the highly pathogenic H5N2 A/turkey/Minnesota/9845-4/2015 virus. No clinical signs and only minimal virus shedding was observed in both vaccinated groups. In contrast, all mock-vaccinated, H5N2-infected chickens shed virus and died within 5 days post challenge. Furthermore, one dose of the live NDV-H5 vaccine also provided protection of 90% chickens immunized by coarse spraying; after exposure to H5N2 challenge, sera from vaccinated surviving chickens neutralized both highly pathogenic H5N1 and H5N8 viruses. Taken together, our results suggest that the NDV-based H5 vaccine is able to protect chickens against intercontinental highly pathogenic H5Nx viruses and can be used by mass application to protect the poultry industry.
Highlights
Pathogenic avian influenza (HPAI) H5N8 viruses have spread globally to many countries; firstly, they were reported in Korea, subsequently in 2014 in China, Japan, Germany, United Kingdom, and Italy.[1,2] A reassortant Highly pathogenic avian influenza (HPAI) H5 viruses including A/chicken/Iowa/04-20/2015 (H5N2) virus that contains5 gene segments (PB2, PA, HA, M, and NS) related to Eurasian HPAI H5N8 was found in Canada in November 2014.3 The US Department of Agriculture (USDA) confirmed HPAI H5N8 and H5N2 virus infections in wild birds in the state of Washington in December, 2014.4 The H5N8, and reassortant H5N2, and H5N1 viruses, in which the H5 gene belongs to clade 2.3.4.4, have been subsequently detected in 21 U.S
The chickens vaccinated with the live Newcastle disease virus (NDV)-H5 virus displayed a similar or even decreased hemagglutination inhibition (HI) titer in most of the birds after booster vaccination; only on 6 birds which had a low titer (10–20) after the first vaccination, an increased HI titer was detected (Fig. 2b). These results indicated that live and inactivated NDV-based H5 vaccine (NDV-H5) vaccines were immunogenic in chickens, whereas the inactivated NDV-H5 vaccine was more immunogenic in chickens than the live NDV-H5 vaccine
The codon-optimized ectodomain of an H5 HA based on the H5N2 A/chicken/Iowa/04-20/2015 virus was cloned into the NDV vector and confirmed by sequencing
Summary
Pathogenic avian influenza (HPAI) H5N8 viruses have spread globally to many countries; firstly, they were reported in Korea, subsequently in 2014 in China, Japan, Germany, United Kingdom, and Italy.[1,2] A reassortant HPAI H5N2 virus that contains. 6 out of 15 chickens immunized with the inactivated NDV-H5 vaccine seroconverted at 2 weeks post the first vaccination with an HI titer ranging from 20 to 80 against the H5 virus; a significantly higher HI titer against the H5 virus was avirulent virus and has been widely used as a vaccine in chickens.[17] NDV-vectored influenza vaccines based on the LaSota found in all birds (HI titer ranges from 10 to 1280) after 2 weeks post booster (Fig. 2a). Regarding the HI titers against NDV LaSota strain have been demonstrated to be safe and efficacious against HPAI or LPAI virus challenge.[9,11,18,19,20,21,22] One advantage of these strain virus, all vaccinated birds with either live or inactivated NDVH5 vaccine seroconverted at 2 weeks post the first vaccination recombinant vaccines is that they can be produced within four to six weeks, which is critical since influenza vaccine should be based on the circulating virus strain in the field. Both live and inactivated NDV-H5 vaccines are able to protect chickens from lethal challenge
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