Co-expression of the Hemagglutinin and Neuraminidase by Heterologous Newcastle Disease Virus Vectors Protected Chickens against H5 Clade 2.3.4.4 HPAI Viruses

Yeonwoo Cho,Barisha Lamichhane,Ishita Roy Chowdhury,Shin-Hee Kim,Abdou Nagy,Siba K Samal

doi:10.1038/s41598-018-35337-z

Abstract

Avian influenza remains an important zoonotic disease with a significant global impact. The spread of H5 highly pathogenic avian influenza (HPAI) viruses (clade 2.3.4.4) by migratory birds has caused outbreaks in wide geographic regions (Asia, Europe, and North America) with great economic losses during 2014–2015. Efficient vaccines and vaccination approaches are needed to enhance protective immunity against HPAI viruses. Although several vaccination strategies have been developed, none has been satisfactory. Our strategy has been to use avirulent vaccine strain of Newcastle disease virus (NDV) as a vaccine vector for HPAI viruses. For poultry vaccination, we previously generated a new platform of chimeric NDV vector to overcome preexisting maternal antibodies to NDV in poultry. In this study, we have generated vaccine candidates targeting H5 clade 2.3.4.4 HPAI viruses by using our chimeric NDV and conventional NDV strain LaSota vectors for a heterologous prime-boost immunization approach. Co-expression of the HA and NA proteins by our vaccine vectors induced enhanced HPAI virus specific immune responses in specific-pathogen free and broiler chickens prior to challenge. Further, these vaccine candidates efficiently protected broiler chickens from mortality, clinical signs, and shedding of homologous and heterologous H5 HPAI viruses and highly virulent NDV, thus providing a dual vaccination approach in the field.

Highlights

In the past 20 years, the number of highly pathogenic avian influenza (HPAI) virus outbreaks has increased, and the goose/Guangdong (Gs/ GD) H5N1 and Mexican H7N3 lineages of viruses have become endemic in poultry[6]
Continuous circulation of HPAIV has led to a reassortant H5N8 virus in which with the HA gene segment is from an H5N1 HPAI virus and other gene segments are from several other AI viruses circulating in eastern China[7]
We previously developed an antigenically distinct chimeric Newcastle disease virus (NDV) vector expressing the protective antigen of H5N1 HPAI (A/Vietnam/1203/2004)[21]

Summary

Introduction

In the past 20 years, the number of HPAI virus outbreaks has increased, and the goose/Guangdong (Gs/ GD) H5N1 and Mexican H7N3 lineages of viruses have become endemic in poultry[6]. The U.S experienced an unprecedented outbreak of H5 HPAI virus with detections of the virus in wild waterfowl and backyard and commercial poultry flocks throughout the Northwestern and upper Midwestern states across the Pacific, Central, and Mississippi wild bird flyways[10,11]. Preexisting maternal antibody to the vector can reduce the efficacy of the vaccine in the field To overcome this limitation, we previously developed an antigenically distinct chimeric NDV vector expressing the protective antigen of H5N1 HPAI (A/Vietnam/1203/2004)[21]. Our study demonstrated that a heterologous prime-boost immunization approach using our chimeric NDV and conventional NDV (LaSota) vectored vaccines efficiently protected commercial chickens against HPAI virus challenge[22]. We have applied our heterologous prime and boost vaccination strategy for efficient control of a novel H5 virus (clade 2.3.4.4) infection in broiler chickens

Methods

Results

Conclusion