Enhancing Malaria Vaccine Development by the Naval Medical Research Center

摘要

DNA plasmid-based malaria vaccines have yielded a 100% immune response, but only 50% protection for 1-2 months. Biopolymeric excipients can provide initial delivery of the vaccine, as well as a controlled release that boosts the immune system to elicit a protective response. This Milestone 2 study evaluated delivery of a plasmid malaria vaccine using a proprietary biopolymeric vehicle. A VR2578 plasmid was able to elicit T cell responses when delivered in saline to mice; however, these results do not correlate to a protective response. The biopolymeric plasmid vaccine also elicited cell-mediated and humoral immune response. However, the number of biopolymeric responders was less than that of the soluble plasmid responders at the same time periods. In comparing these in vivo results with the in vitro studies of plasm id release from the biopolymeric excipient, the total dose released during the first 24 hours after each immunization was about 18% of the total contained within the excipient. Thus, mice received significantly less in the initial period when compared to the saline groups. The results suggest that the delivery rate and the time required to elicit an immune response affects vaccine performance. Given that a robust response can be achieved in follow-on studies by optimizing the dose in polymer, it remains the hypothesis that the controlled release element of the excipient can confer protection.