Engineered viral vaccine constructs with dual specificity: Avian influenza and Newcastle disease

Abstract

Avian influenza viruses of the H5 and H7 hemagglutinin subtypes, and Newcastle disease virus (NDV), are important pathogens in poultry worldwide. Specifically, the highly pathogenic H5N1 avian influenza virus is a particular threat because it has now occurred in more than 40 countries on several continents. Inasmuch as most chickens worldwide are vaccinated with a live NDV vaccine, we embarked on the development of vaccine prototypes that would have dual specificity and would allow a single immunization against both avian influenza and Newcastle disease. Using reverse genetics, we constructed a chimeric avian influenza virus that expressed the ectodomain of the hemagglutinin-neuraminidase gene of NDV instead of the neuraminidase protein of the H5N1 avian influenza virus. Our second approach to creating a bivalent vaccine was based on expressing the ectodomain of an H7 avian influenza virus hemagglutinin in a fusogenic and attenuated NDV background. The insertion into the NDV genome of the foreign gene (containing only its ectodomain, with the transmembrane and cytoplasmic domains derived from the F protein of NDV) resulted in a chimeric virus with enhanced incorporation of the foreign protein into virus particles. A single immunization of chickens with this improved vaccine prototype virus induced not only a 90% protection against an H7N7 highly pathogenic avian influenza virus, but also complete immunity against a highly virulent NDV. We propose that chimeric constructs should be developed for convenient, affordable, and effective vaccination against avian influenza and Newcastle disease in chickens and other poultry.chicken ͉ Newcastle disease virus ͉ pandemic ͉ avian influenza virus ͉ hemagglutinin

Newcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens

“…nicity (38). Alternatively, the reduced immunogenicity of NDV-BC/S1 might mean that the S2 domain of the S protein contains or contributes to one or more important neutralizing epitopes (39).…”

“…Moreover, presence of the S insert did not increase pathogenicity of the virus in birds, as evaluated by the mean embryo death time. In recent studies, the insertion of foreign genes, including that encoding the hemagglutinin protein of highly pathogenic avian influenza virus, into the genomes of lentogenic or mesogenic strains of NDV resulted in reduced rather than increased pathogenicity in birds, even when the foreign glycoprotein was from a highly pathogenic avian influenza virus and was incorporated into the vector particle (38,43). Taken together, these data suggest that the vaccine constructs present no environmental or agricultural risk, although this possibility will continue to be carefully monitored.…”

Influence of insertion site of the avian influenza virus haemagglutinin (HA) gene within the Newcastle disease virus genome on HA expression

“…This problem could be overcome by vector vaccines. The successful use of NDV as a vector for the expression of AIV HA has been described in different studies, where the foreign gene was integrated between the P and M genes (DiNapoli et al, 2010;Ge et al, 2007;Nakaya et al, 2001;Park et al, 2006) or the F and HN genes (Schröer et al, 2009;Veits et al, 2006). In both cases, the recombinant viruses conveyed protection against NDV, as well as against influenza infection of the corresponding subtype.…”

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“…This statistical improvement of protection in the embedded birds could be due to the presence of conserved homologous fusion protein of genotype VI in the inactivated strain present in the autogenous vaccine and in the live prevalent field strains. Other researchers documented an improvement in protection of broilers due to the presence of similar fusion antigens in the NDV vaccine and in the field v-NDV strains [33]. The acquired immunity, by the major flocks versus the embedded ones, to the H-protein of the v-NDV (genotype VI) strain that was incorporated in the HI-test, is shown in Table 4.…”