tions living in endemic areas but are quite similar to the needs in the civilian traveler market. Ideally, a high level of efficacy against infection is required for a relatively short period of time (e.g., 6 months). The most likely scenario is a “first-generation vaccine” that is a valuable adjunct to chemoprophylaxis, followed by development of an “ideal” vaccine that could be used alone for malaria prevention. A first-generation vaccine providing about 60 percent protection against clinical disease (with a lower limit of 30 percent for the 95 percent confidence interval around the 60 percent point estimate of efficacy) for 6 months is regarded as useful. A second-generation “ideal” vaccine, which could be used to replace the routine use of chemoprophylaxis, would have to provide greater than 95 percent protection against infection over a longer time period.
No vaccine candidates are currently in development that are likely to meet the military requirements for a first-generation vaccine in the next 5 to 10 years. A more realistic target date for availability of a licensed vaccine (even with more resources) is 2015–2020.
The program to develop a malaria vaccine for U.S. military personnel should focus on (and have the capacity to conduct) clinical efficacy trials in immunologically naïve military personnel (off and on chemoprophylaxis) in endemic areas, for which the field sites currently maintained by the DoD are a critical resource. Suggestions for the design and size of the trials necessary to demonstrate the suggested efficacy for the first-generation vaccine are provided in Appendix C to this report.
Research on all three main malaria vaccine development strategies— gene-based (e.g., DNA, plasmid, or viral vector vaccines), protein-based, and attenuated sporozoite approaches—should be continued. However, as research progresses, the number of candidate products must be limited by dropping those that perform less well. The MIDRP Malaria Vaccine Program should aggressively move into clinical trials to test specific vaccine products, and select two to three leads at phase 1 and one at phase 2 for each strategy. For protein-based and gene-based strategies, the focus should be on specific vaccine products that combine the lead antigens (CSP, SSP-2/TRAP, LSA-1, AMA-1, and MSP-1) including their use in heterologous prime-boost combinations.
Given the limited time available for this review, the committee did not wish to give more detailed specific advice other than to narrow the focus to a smaller number of candidate antigens. Despite having extensive expertise in all scientific aspects of the program, the committee concluded that instead of offering one-time advice on specific antigens or approaches, it would be more productive to recommend a structure and process for ongoing review and decision making about the scientific direction of the work.