A new study by Christopher Plowe and colleagues (University of Maryland School of Medicine) on a malaria vaccine used at a testing site in Mali calls into question whether the best vaccine was chosen to be tested at this particular site.
The development of an effective malaria vaccine is not easy, in part because there are different strains of the Plasmodium parasite that causes the disease. The different strains carry different variants (alleles) of the genes encoding parasite components (antigens) used in test vaccines, which means that the parasites causing infection in a given location may differ from the ones used for vaccination. If this is the case, the immune response generated by the vaccine might be less effective or even ineffective.
Plowe and colleagues investigated an antigen called MSP-119, which is included in a candidate vaccine that was recently tested in Mali. The MSP-119 gene contains six polymorphisms (variations) that can occur in various combinations (haplotypes); the candidate vaccine contained MSP-119 from the 3D7 strain of P. falciparum.
The researchers used DNA sequencing to examine the MSP-119 gene in more than 1300 malaria infections in 100 Malian children. They compared the frequencies of 14 different MSP-119 haplotypes over three years, in three age groups, and in consecutive infections within individuals. They found that the frequency of individual MSP-119 haplotypes fluctuated in their study population, but that the P. falciparum 3D7 MSP-119 haplotype was present in only 16% of the infections. (In contrast, combinations found in P. falciparum FVO and FUP strains were each present in about 40% of the infections.)
These findings show that most parasites at the Malian vaccine test site make a different form of MSP-119 than the one contained in the vaccine. Although early results from field trials suggest that the 3D7-derived vaccine may provide some protection against the more common FVO and FUP strains, the immunity stimulated by the vaccine might not be optimal. If this turns out to be the case, a FVO- or FUP-derived vaccine might be more effective in Mali than the 3D7-derived vaccine, though not necessarily elsewhere.
More generally, these results show the importance of determining the genetics of pathogen populations before starting vaccine trials. Without this information, a vaccine's ability to prevent infections with specific parasite strains cannot be determined accurately and potentially useful vaccines might be abandoned if they are tested on inappropriate populations.
As Colin Sutherland (London School of Hygiene and Tropical Medicine) writes in an accompanying Perspective, "this study provides ample warning that analysis of antigen diversity in the target population ... should be part of the intelligence gathering undertaken when planning intervention studies in the first place".
Citation: Takala SL, Coulibaly D, Thera MA, Dicko A, Smith DL, et al. (2007) Dynamics of polymorphism in a malaria vaccine antigen at a vaccine-testing site in Mali. PLoS Med 4(3): e93.
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