Recombinant vaccines protect poultry from avian flu, Newcastle disease

Jun 2, 2006 (CIDRAP News) – Two vaccines protected chickens against Newcastle disease (ND) and avian influenza and may provide approaches for producing human vaccines against the H5N1 avian flu virus, according to two studies published in the May 26 issue of the Proceedings of the National Academy of Sciences.

The new vaccines relied on recombinant methodology to create chimeric viruses containing portions of both ND and avian influenza virus (AIV) genomes. Recombinant viruses were employed as bivalent, live-virus vaccines to immunize chickens against avian influenza. Immunized chickens were later challenged for both diseases and also tested for viral shedding.

Both vaccines protected animals from ND and AIV. One vaccine also had the advantage of allowing serologic discrimination between vaccinated and field-infected birds, an important aid for controlling spread among poultry flocks. Because of concerns about potential recombination between the vaccine strain and native viruses, vaccinated chickens were also tested for recombinant viruses. Analysis did not reveal any evidence of vaccine-derived recombinant viruses or enhanced virulence.

Vaccine combines Newcastle, H5N2 viruses
Jutta Veits and colleagues cloned a full-length copy of a low-pathogenic ND strain and then inserted the coding sequence for the hemagglutinin of a highly pathogenic avian influenza virus (H5N2) between two ND virus genes. The resultant product was an ND virus that expressed the hemagglutinin H5 (HA) of avian influenza. The team synthetically modified this virus to enhance production of HA transcripts and protein and to minimize potential viral recombination.

Twenty-five 3-week old, pathogen-free chickens were immunized by oculonasal administration of the modified virus. Chickens tested 3 weeks after inoculation had ND- and AIV-specific antibodies and were also protected against clinical challenges with lethal doses of either virus, the report says. No AIV was shed from vaccinated chickens. Recombinant viruses isolated from chickens that had been inoculated with the vaccine at 1 day old were found to be benign rather than virulent.

Enhanced virulence and viral shedding from vaccinated animals, two concerns about recombinant vaccines, were eased by these findings, according to the article. Recombination events among vaccine and wild viruses may produce more virulent strains, and propagation of AIV among vaccinated birds might mask such events, making control more difficult. In addition, shedding of virus could promote spread of disease.

An important characteristic of this vaccine, the authors write, is that it allows serologic discrimination between vaccinated and wild virus–infected animals. Testing detected antibodies against the nucleoprotein of AIV. This antibody is absent in vaccinated chickens but present and identifiable in vaccinated chickens that are infected with AIV.

Such a vaccine would allow identification and culling of birds infected after vaccination. It thus circumvents the problem of undetected circulation of virus among vaccinated birds and represents a potentially important tool for controlling AIV. The authors state that this vaccine "is suitable as a bivalent vaccine against ND and AIV and may be used as a marker vaccine for the control of avian influenza."

Another recombinant approach
A second group of researchers used reverse genetics to produce vaccines for negative-stranded RNA viruses that also protected chickens against a highly pathogenic AIV (H5N1) and a highly virulent ND. Man-Seong Park and colleagues constructed an AIV vaccine that substituted the "a" portion of the hemagglutinin-neuraminidase gene of ND for the neuraminidase protein gene of the H5N1 avian influenza virus as one approach. These constructs were used to test modified viral sequences aimed at reducing potential spontaneous conversion to virulence and for making an effective bivalent vaccine.

The resultant bivalent vaccine (rNDV/F3aa-chimeric H7) was based on expression of part of H7 AIV hemagglutinin in a truncated and attenuated ND background. The chimeric virus enhanced the incorporation of the foreign protein into virus particles and reduced concerns about the other vaccine's potential for spontaneous conversion to virulence.

Twenty white Leghorn chickens were vaccinated with the bivalent vaccine by eyedrop application, with half receiving one dose and half getting two doses. Vaccinated chickens were challenged with both diseases. A single immunization induced 90% protection against H7N7, a highly pathogenic AIV strain, and complete immunity against a highly virulent ND virus.

The authors suggest that chimeric constructs might serve as the basis for developing convenient, affordable, and effective vaccination against these diseases in chickens and other poultry. A similar approach might also be used to produce human viral vaccines, provided suitable viral vectors can be found for humans. Humans are not susceptible to Newcastle disease, so developing such a vaccine would hinge on using a virus that easily infects people to get a safe and effective immune system response.

Veits J, Wiesner D, Fuchs W, et al. Newcastle disease virus expressing H5 hemagglutinin gene protects chickens against Newcastle disease and avian influenza. Proc Natl Acad Sci 2006 May 23;103(21):8197-202 [Abstract]

Park MS, Steel J, Garcia-Sastre A, et al. Engineered viral vaccine constructs with dual specificity: avian influenza and Newcastle disease. Proc Natl Acad Sci 2006 May 23;103(21):8203-8 [Full text]

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