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Effects of Passive Immunization on Immunogenicity of Filovirus Vaccines


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The overall research idea of this proposal is to ascertain the feasibility of providing short-term protection against Ebola virus infection while co-administering Ebola virus vaccines to provide long-term protection against disease. Ebola virus vaccine candidates (a live replicating vesicular stomatitis virus (VSV) expressing Ebola-GP and a replication-deficient adenovirus (AdV) expressing Ebola GP) have been used in humans. For therapeutic purposes, monoclonal antibodies (ZMapp, mAb114) and antiviral small molecules (Favipiravir, Remdesivir) are also being tested in human infections. However, neither antibody therapy nor small molecule inhibitors of Ebola virus replication will protect against infection long-term, and vaccines do not provide immediate protection. To that end, this proposal will test multiple strategies to combine therapeutic drugs with vaccines to generate rapid short-term as well as long-term protection against Ebola virus. In the first year we found that administration of neutralizing antibodies had an effect on the short-term immunogenicity of both VSV and AdV vaccines. There was no significant effect on longer-term antibody responses for the VSV vaccine, and a variable effect for the AdV vaccine. However, there was no inhibition of antibody cocktail levels caused by vaccination. Therefore, the first and second years have demonstrated regimens that may provide both short-and long-term immunity.



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