SBIR-STTR Award

The aim of this proposal is to develop an effective and rapid method for disrupting the poultry-to- human transmission of avian influenza by in ovo injection of flu vaccines that can be mass- administered with a mechanized injector. The hypothesis is that mass-vaccination of poultry against an outbreak of avian influenza reduces the dissemination of the virus to new flocks and consequently the risk to humans. As avian influenza gets more and more deadly, it is increasingly urgent to produce vaccines rapidly in response to an unprecedented escalation in demand. Emerging evidence suggests that poultry can be immunized en masse by in ovo administration of DMA vaccines and non-replicating adenovirus (Ad)-vectored vaccines without masking infections. Both vaccines are produced by molecular biology techniques without the requirement to propagate lethal virus strains. These studies will compare these two vaccination modalities in their potency to mobilize the immune repertoire toward a beneficial immune protection against avian influenza virus infection in chickens. In this project, efficacy of a DMA vaccine will be compared to that induced by a non-replicating Ad vector encoding the same codon-optimized A/Turkey/Wisconsin/68 hemagglutinin gene. Both vaccines will be injected into the amnion of chicken embryos. The tetradecylmaltoside surfactant will be evaluated as a gene delivery enhancer for both classes of vaccines. Hemagglutination- inhibition (HI) antibody titers against the A/Turkey/Wisconsin/68 virus will be analyzed in chickens post-hatch. Ad vectors will be generated using a new AdHigh system developed for manufacturing replication-competent Ad (RCA)-free Ad vectors at high speed and high titer. The overall goal of these experiments is to determine whether high HI antibody titers against avian influenza virus can be elicited in chickens by in ovo injection of non-replicating vectored vaccines without using the avian influenza virus itself, and thus avoiding the related biohazard of growing a deadly virus strain as well as difficulty of distinguishing the effect of vaccination from that of infection

The aim of this proposal is to develop an effective and rapid method for disrupting the poultry-to-human transmission of avian influenza by in ovo injection of adenovirus-vectored avian influenza vaccines that can be mass-produced in cultured cells and mass-administered with a mechanized injector. The hypothesis is that mass-vaccination of poultry against an outbreak of avian influenza reduces the dissemination of the virus to new flocks and consequently the risk to humans. As avian influenza gets more and more deadly, it is increasingly urgent to produce vaccines rapidly in response to an unprecedented escalation in demand. We have demonstrated that chickens can be immunized against highly pathogenic avian influenza viruses by in ovo administration of non-replicating adenovirus vectors encoding an avian influenza virus hemagglutinin. In contrast to conventional avian influenza vaccines, this new class of avian influenza vaccine does not mask natural infections by an avian influenza virus. The recombinant adenovirus vector can be rapidly generated using Vaxin's proprietary AdHigh system without the requirement to propagate lethal avian influenza viruses. The Phase II studies will further explore the potential of an adenovirus-vectored in ovo vaccine in mobilizing the immune repertoire toward a beneficial immune protection against avian influenza in chickens. In this project, the potential for an adenovirus-vectored in ovo avian influenza vaccine to immunize breeder hens and progeny chickens will be investigated; the fate of adenovirus vectors in chickens following in ovo administration will be determined; vaccination of chickens against multiple avian diseases by adenovirus-vectored in ovo vaccines will be developed; the compatibility between an adenovirus-vectored in ovo vaccine and the DIVA strategy for immunization of poultry will be defined; and the potency of adenovirus-vectored in ovo vaccines under field conditions will be analyzed. The overall goal of these experiments is to develop a new generation of avian influenza vaccine that can be rapidly manufactured and administered for mass-immunization of poultry in response to a crisis.

Public Health Relevance:
Avian influenza represents a major impending threat to public health. Mass-vaccination of poultry flocks against this deadly disease will be a crucial tool for reducing the rapid spread of the anticipated human pandemic. Vaccinating eggs before they hatch is much faster, easier, and less expensive than vaccinating live birds. The aim of this proposal is to develop a safe and effective vaccine which can rapidly vaccinate eggs to stop or slow the spread of the avian influenza, thus protecting humans as well as a significant food source. A genetically modified adenovirus is the basis of this new type of vaccine.

Public Health Relevance:
This Public Health Relevance is not available.

Thesaurus Terms:
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