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NC State Biochemistry

 

 

Raquel Hernandez
Research Associate Professor of Molecular and Structural Biochemistry

Education:
PhD, University of Texas

Contact:
Office: 346 Polk Hall
Phone:
   Office: 919.515.5765
   Fax: 919.515.2047
Email: Raquel Hernandez

Dr. Hernandez

Website: Visit our Lab Home Page

Research Areas: Vaccines against arthropod vectored virus diseases

Arthropod bourne viruses are major sources of human disease.  They are collectively second only to malaria as world health problem number one.  About 700 of these agents are presently known with emerging strains appearing annually.  For one of these agents, Dengue Fever, approximately 100 million cases are reported annually with many more cases unreported. About 2.5 billion people are at risk of contracting this disease annually. Despite the enormous economic and medical impact of these agents very few effective vaccines exist for their control.  Live virus vaccines, which are the most effective forms of vaccines, have been particularly difficult to produce.  

We have developed a technique for the production of live virus vaccines for arthropod vectored viruses.  This technology is based on the discovery that evolution has provided these viruses with genetic information essential for replication in one of the two hosts (mammals and insects) but not the other.  We have identified genetic elements required for efficient replication in the mammalian host and removed them.  These deletion mutations restrict the growth of the virus to the insect host resulting in a host range mutation that is a deletion with little prospect of reversion to wild type.  Injection of the insect produced virus into mammals results in the production of high titers of neutralizing antibody and protection against challenge with wild type virus in the absence of disease.  In principle this technology will produce a live virus vaccine against any of these arthropod vectored diseases for which a cDNA clone can be produced.  The significance of this possibility is obvious.


We have successfully produced host range mutations in all 4 serotypes of dengue virus which are the result of deletions in the membrane spanning domain of the virus envelope protein.  We have shown that these viruses grow efficiently in insect cells but poorly in mammalian cells.  In collaboration with the company "Arbovax" we have shown that these mutations elicit protective immunity in mice and in the case of serotype 2 dengue virus in monkeys. A tetravalent formulation designed to produce protective immunity against all 4 serotypes has just  completed testing in monkeys.  Significant effort will be dedicated to the analysis of the outcome of this trial.