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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
2R44AI068285-02
Application #
7541315
Study Section
Special Emphasis Panel (ZRG1-IMM-K (12))
Program Officer
Cassels, Frederick J
Project Start
2006-03-15
Project End
2011-08-31
Budget Start
2008-09-05
Budget End
2009-08-31
Support Year
2
Fiscal Year
2008
Total Cost
$332,379
Indirect Cost
Name
Vaxin Inc.
Department
Type
DUNS #
032198363
City
Gaithersburg
State
MD
Country
United States
Zip Code
20878
Tang, De-Chu C (2017) Noninvasive vaccination as a casus belli to redeem vaccine value in the face of anti-vaccine movements. Integr Mol Med 4:
Tang, De-chu Christopher (2014) A trail blazed through DNA vaccine, noninvasive vaccine, and innate-adaptive immunity duo. Hum Vaccin Immunother 10:2143-6
Tang, De-Chu Christopher; Nguyen, Huan Huu (2014) The Yin-Yang arms of vaccines: disease-fighting power versus tissue-destructive inflammation. Expert Rev Vaccines 13:417-27
Zhang, Jianfeng (2012) Advances and future challenges in recombinant adenoviral vectored H5N1 influenza vaccines. Viruses 4:2711-35
Zhang, Jianfeng; Tarbet, E Bart; Toro, Haroldo et al. (2011) Adenovirus-vectored drug-vaccine duo as a potential driver for conferring mass protection against infectious diseases. Expert Rev Vaccines 10:1539-52
Zhang, Jianfeng; Tarbet, E Bart; Feng, Tsungwei et al. (2011) Adenovirus-vectored drug-vaccine duo as a rapid-response tool for conferring seamless protection against influenza. PLoS One 6:e22605
Toro, Haroldo; van Ginkel, Frederik W; Tang, De-Chu C et al. (2010) Avian influenza vaccination in chickens and pigs with replication-competent adenovirus-free human recombinant adenovirus 5. Avian Dis 54:224-31
Singh, Shailbala; Toro, Haroldo; Tang, De-Chu et al. (2010) Non-replicating adenovirus vectors expressing avian influenza virus hemagglutinin and nucleocapsid proteins induce chicken specific effector, memory and effector memory CD8(+) T lymphocytes. Virology 405:62-9
Toro, H; Tang, D C (2009) Protection of chickens against avian influenza with nonreplicating adenovirus-vectored vaccine. Poult Sci 88:867-71
Tang, De-chu C; Zhang, Jianfeng; Toro, Haroldo et al. (2009) Adenovirus as a carrier for the development of influenza virus-free avian influenza vaccines. Expert Rev Vaccines 8:469-81

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