Chimeric Newcastle Disease Virus Protects Chickens against Avian Influenza in the Presence of Maternally Derived NDV Immunity

Abstract

Newcastle disease virus (NDV), an avian paramyxovirus type 1, is a promising vector for expression of heterologous proteins from a variety of unrelated viruses including highly pathogenic avian influenza virus (HPAIV). However, pre-existing NDV antibodies may impair vector virus replication, resulting in an inefficient immune response against the foreign antigen. A chimeric NDV-based vector with functional surface glycoproteins unrelated to NDV could overcome this problem. Therefore, an NDV vector was constructed which carries the fusion (F) and hemagglutinin-neuraminidase (HN) proteins of avian paramyxovirus type 8 (APMV-8) instead of the corresponding NDV proteins in an NDV backbone derived from the lentogenic NDV Clone 30 and a gene expressing HPAIV H5 inserted between the F and HN genes. After successful virus rescue by reverse genetics, the resulting chNDVFHN PMV8H5 was characterized in vitro and in vivo. Expression and virion incorporation of the heterologous proteins was verified by Western blot and electron microscopy. Replication of the newly generated recombinant virus was comparable to parental NDV in embryonated chicken eggs. Immunization with chNDVFHN PMV8H5 stimulated full protection against lethal HPAIV infection in chickens without as well as with maternally derived NDV antibodies. Thus, tailored NDV vector vaccines can be provided for use in the presence or absence of routine NDV vaccination.

Viral vector-based influenza vaccines

“…148 Consequently, a recombinant NDV expressing HA genes of A(H5N1) viruses has been licensed as a poultry vaccine in some countries and was shown to have a protective effect against challenge infection with A(H5N1) viruses in chickens and ducks in various studies. [149][150][151][152][153][154][155][156][157][158][159][160][161][162][163] The NDV based A(H5N1) vaccine offered only partial cross-clade protection, but was immunogenic in the presence of maternal antibodies. 162,163 Expression or coexpression of NA by NDV did not improve immunogenicity in chickens.…”

Ngari Virus in Goats during Rift Valley Fever Outbreak, Mauritania, 2010

“…Only sample 51 displayed a cytopathic effect after 72 h and was further analyzed. We isolated the viral RNA from cell culture with TRIzol reagent (Invitrogen, Carlsbad, CA, USA) and used it to prepare a sequencing library according to a recently published protocol ( 7 ) but using Illumina adaptors (Illumina, San Diego, CA, USA). We sequenced the resulting library using the Illumina MiSeq instrument with v2 chemistry.…”

Avian paramyoxvirus-8 immunization reduces viral shedding after homologous APMV-8 challenge but fails to protect against Newcastle disease

“…This is in agreement with earlier experiments of Nayak and colleagues [ 20 ]: They observed mortality up to day 11 in APMV-8 preinfected chickens, compared to 9 days in non-immunized control chickens, and one out of five chickens survived challenge with 200 chicken lethal dose 50 (CLD 50 ) of virulent NDV strain Texas-GB. It is interesting to note, that also after vaccination with chimeric APMV-1/APMV-8 vector vaccine ( ch NDV FHN PMV8 H5 ) a comparable delay of 2 days in the clinical course of ND was observed applying the same NDV challenge model [ 13 ]. Apparently, this effect of retarded clinical onset of disease is independent of the subtype.…”

“…highly pathogenic avian influenza virus (HPAIV) [ 11 , 12 ]. To avoid interference by maternal NDV antibodies with vaccine vector performance, we created a chimeric virus ( ch NDV FHN PMV8 H5 ) by substituting the envelope glycoproteins hemagglutinin-neuraminidase (HN) and fusion protein (F) of NDV by those of APMV-8 and expressing H5 of HPAIV [ 13 ]. APMV-8 was chosen as donor of HN and F because of its apathogenicity for poultry [ 14 ], description of only weak cross-reactivity between APMV-1 and APMV-8 [ 15 , 16 ] and low prevalence [ 17 – 19 ].…”