Immunization of Chickens with Newcastle Disease Virus Expressing H5 Hemagglutinin Protects against Highly Pathogenic H5N1 Avian Influenza Viruses

Abstract

BackgroundHighly-pathogenic avian influenza virus (HPAIV) and Newcastle disease virus (NDV) are the two most important poultry viruses in the world. Natural low-virulence NDV strains have been used as vaccines over the past 70 years with proven track records. We have previously developed a reverse genetics system to produce low-virulent NDV vaccine strain LaSota from cloned cDNA. This system allows us to use NDV as a vaccine vector for other avian pathogens.Methodology/Principal FindingHere, we constructed two recombinant NDVs (rNDVs) each of which expresses the hemagglutinin (HA) gene of HPAIV H5N1strain A/Vietnam/1203/2004 from an added gene. In one, rNDV (rNDV-HA), the open reading frame (ORF) of HA gene was expressed without modification. In the second, rNDV (rNDV-HAF), the ORF was modified so that the transmembrane and cytoplasmic domains of the encoded HA gene were replaced with those of the NDV F protein. The insertion of either version of the HA ORF did not increase the virulence of the rNDV vector. The HA protein was found to be incorporated into the envelopes of both rNDV-HA and rNDV-HAF. However, there was an enhanced incorporation of the HA protein in rNDV-HAF. Chickens immunized with a single dose of either rNDV-HA or rNDV-HAF induced a high titer of HPAIV H5-specific antibodies and were completely protected against challenge with NDV as well as lethal challenges of both homologous and heterologous HPAIV H5N1.Conclusion and SignificanceOur results suggest that these chimeric viruses have potential as safe and effective bivalent vaccines against NDV and. HPAIV. These vaccines will be convenient and affordable, which will be highly beneficial to the poultry industry. Furthermore, immunization with these vaccines will permit serological differentiation of vaccinated and avian influenza field virus infected animals.

Induction of respiratory immune responses in the chicken; implications for development of mucosal avian influenza virus vaccines

“…In humans, HA-specific IgA in nasal washes is considered to be an important mediator in protection from influenza infection (Clements et al 1986). Also in chicken, Ig are involved in protection against AIV as birds that are protected by vaccination have high serum titres of influenza-specific Ig (Kumar et al 2007;Maas et al 2009;Nayak et al 2009). The role of respiratory Ig in AIV-specific immunity has previously been investigated after vaccination at the level of secreted Ig in tears and serum and ASC in HG.…”

“…The role of respiratory Ig in AIV-specific immunity has previously been investigated after vaccination at the level of secreted Ig in tears and serum and ASC in HG. It is known that Ig are involved in protection against AIV as birds that are protected by vaccination have high serum titres of influenza-specific Ig (Kumar et al 2007;Maas et al 2009;Nayak et al 2009). Van Ginkel et al (2008) studied mucosal and systemic humoral immune responses following ocular influenza vaccination with a H5-expressing replication competent adenovirus (RCA)-free human E1/E3-defective Ad5 vector.…”

“…The recombinant fowl pox vaccine induced good protection from heterologous challenge (Swayne et al 2007), but can interfere with preexisting immunity against fowl pox. HA-expressing NDV vector vaccines can be applied by spray or in drinking water and have shown to protect against challenge infection in chicken Nayak et al 2009;Schroer et al 2011). Similar to the fowl pox vaccine, the NDV vector vaccine can also interfere with preexisting NDV immunity induced by NDV vaccination.…”

Comparison of single 1-day-old chick vaccination using a Newcastle disease virus vector with a prime/boost vaccination scheme against a highly pathogenic avian influenza H5N1 challenge

“…In some circumstances, well-monitored vaccination can be an additional tool for an effective control programme of AI in combination with good biosecurity practices, education about prevention, preventive culling, early diagnosis, and surveillance to detect the disease and infection. Several AI vaccines, such as inactivated , live attenuated vectored Ge et al, 2007;Römer-Oberdörfer et al, 2008;Nayak et al, 2009;Pavlova et al, 2009;Ramp et al, 2011;Lardinois et al, 2012), subunit (Swayne et al, 2001), reassortant (Lee et al, 2013) or DNA vaccines (TorrieriDramard et al, 2011), have been shown to protect against HPAI, but only inactivated whole AI virus vaccines and viral vectored vaccines based on fowlpox virus or Newcastle disease virus (NDV) vectors (Swayne & Kapczynski, 2008) have so far been licensed in some countries.…”

“…Indeed, similar to live NDV vaccines, rNDV-AI vaccines induce NDV-specific antibodies and provide excellent clinical and virological protection against velogenic NDV challenges. Most of these vaccines afforded good clinical and virological protection against homologous H5N1 HPAI challenges with minimal Nayak et al, 2009;Lardinois et al, 2012) or high (Ge et al, 2007) AIVspecific antibodies. However, a lower level of protection could be observed after heterologous challenge, underlining the importance of the homology between the H5 insert vaccine and the HPAI challenge strain (Ramp et al, 2011;Lardinois et al, 2012).…”