Enhancing the Immunogenicity of a Dengue-2 DNA Vaccine With Adjuvants and Anti-FCyRI Antibodies
Final rept. 1 Mar 2005-28 Feb 2006
NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD
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The objective is to use adjuvants to enhance the immunogenicity of a dengue DEN DNA vaccine. The adjuvants to be evaluated in this project included aluminum phosphate, tetanus toxoid and anti-Fc R monoclonal antibodies chemically linked to the DNA vaccine. Multiple attempts to link the anti-Fc R monoclonal antibody to the DNA vaccine resulted in a poor efficiency in the linkage reaction using thiol linkage chemistry. An alternative approach using hydrazine and aldehyde linkage methods were used but failed to improve DNAantibody conjugation efficiency. Experiments were initiated to evaluate the ability of tetanus toxoid TT to enhance the immunogenicity of the DEN DNA vaccine. The antibody responses to the vaccine given IM were enhanced slightly by combining it with TT. However, the ELISA and neutralizing antibody levels were inferior to the levels obtained with ID administration of the vaccine alone. When using low doses of the vaccine given by Biojector, TT appeared to have an inhibitory effect. Aluminum Phosphate was demonstrated to slightly enhance anti-dengue neutralizing antibody responses, only when the DNA vaccine was given ID at suboptimal doses. There was essentially no effect when the vaccine was administered IM.
- Medicine and Medical Research