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Development of Recombinant Pandemic Influenza Vaccines
Institution: University of Arkansas for Medical Sciences, Little Rock, AR
Principal Investigator: Xuming Zhang, PhD
Expected Product: High-yield vaccine candidates that are safe and effective for human pandemic influenza.
Description: Highly
pathogenic avian H5N1 influenza viruses continue to circulate
in animals and infect humans with high mortality in many parts
of the world, particularly in Asia, in recent years. Adaptation
to humans or genetic reassortment with human influenza viruses
could result in pandemic strains with devastating consequences.
This poses a significant threat to public health worldwide. Development
of effective vaccines for preventing such a potential pandemic
influenza is therefore of great urgency. However, current H5N1
vaccine candidates tested in humans generally have poor immunogenicity.
In addition, avian H5N1 influenza viruses grow poorly in embryonated
chicken eggs, which makes them difficult for mass production.
The long-term goal of this project is to develop high-yield vaccine
candidates that are safe and effective for human pandemic influenza.
Two specific aims are proposed in this project. In aim 1, recombinant
influenza viruses will be generated by reverse genetics system.
The recombinant influenza viruses will contain the genetic background
of the human A/Puerto Rico/8/34(H1N1) virus that is the highly
mouse-adapted, low-virulent vaccine strain, while the hemagglutinin
and neuraminidase genes are replaced with genetically altered
counterparts of the avian A/Hong Kong/156/97 (H5N1) or A/Vietnam/1203/2004
(H5N1) viruses. Such recombinant viruses are expected to be safe
and effective vaccine candidates for H5N1 human pandemic. Their
growth properties will be determined both in cell cultures and
embryonated chicken eggs, and their antigenicity will be evaluated
in vitro using reference antibodies. In aim 2, the safety and
immunogenicity of the candidate recombinant vaccines will be
evaluated in a mouse model. The ability of the purified hemagglutinin
proteins, inactivated whole viruses, and live viruses to induce
specific neutralizing antibody response against the H5N1 subtype
will be studied in naive mice and in mice primed with H1N1 human
viruses. This exploratory project is designed to test the feasibility
of such genetic approaches for rapid generation of pandemic influenza
vaccines. If successful, it will identify promising candidate
vaccines for further testing the safety, immunogenicity and efficacy
in chicken and ferret models. Candidate vaccines will be produced
under the current Good Manufacturing Practice for human testing
in the future. |
