However there is concern over the large number of vaccine candidate constructs currently under evaluation, with numerous external partners involved. Lack of financial independence sometimes puts the partners in control. The pathway from preclinical research to clinical trials for the numerous gene-based products is sometimes not clear. In some cases the partners appear to be excessively influencing the research agenda while simultaneously imposing restrictions on what can be accomplished. For example, the use of two different adenovirus vectors needs to be reconciled, as do the two adjuvants being used by GSK. Head-to-head efficacy comparisons of constructs and vectors from different commercial partners are unlikely to occur and may not be necessary in any case. Other decision methods such as standardized comparative immunogenicity tests could be used to narrow the scope.

Increased focus on a smaller number of potential constructs is required, but the program lacks a prospective process or objective criteria for down-selection of candidates. Performance should be evaluated by established humoral and cellular immune response assays in a reference laboratory if possible, and additionally for blood-stage candidate vaccines by a functional immune response assay such as the merozoite growth inhibition assay. Development of these mutually agreed upon criteria should be the responsibility of Joint Task Force for Malaria Vaccine (JTF-MV) discussed below. Down-selection criteria should utilize all available information from the rapidly progressing HIV vaccine field to assess vaccine delivery platform leads.

The committee noted that increased focus on fewer candidate antigens and constructs does not imply decreased funding as development of even one of the current constructs will require a greatly increased budget. Maintaining a larger number of constructs is likely to lead to failure to complete development or to delay substantially the development of candidates.

From the information presented, the committee felt that there is no vaccine candidate yet available that is likely to meet the military requirements (even the suggested revised requirements) in the next 5 to 10 years. The likelihood of eventual success appears to be high, but a more realistic target date for availability of a licensed P. falciparum vaccine (even with more resources) is 2015–2020.

Recommendation 4.3: 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



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