Abstract
BackgroundMosquito stage malaria vaccines are designed to induce an immune response in the human host that will block the parasite's growth in the mosquito and consequently block transmission of the parasite. A mosquito membrane-feeding assay (MFA) is used to test transmission-blocking activity (TBA), but in this technique cannot accommodate many samples. A clear understanding of the relationship between antibody levels and TBA may allow ELISA determinations to be used to predict TBA and assist in planning vaccine development.MethodsRabbit anti-Pfs25 sera and monkey anti-Pvs25 sera were generated and the antibody titers were determined by a standardized ELISA. The biological activity of the same sera was tested by MFA using Plasmodium gametocytes (cultured Plasmodium falciparum or Plasmodium vivax from malaria patients) and Anopheles mosquitoes.ResultsAnti-Pfs25 and anti-Pvs25 sera showed that ELISA antibody units correlate with the percent reduction in the oocyst density per mosquito (Spearman Rank correlations: 0.934 and 0.616, respectively), and fit a hyperbolic curve when percent reduction in oocyst density is plotted against antibody units of the tested sample. Antibody levels also correlated with the number of mosquitoes that failed to become infected, and this proportion can be calculated from the reduction in oocyst numbers and the distribution of oocysts per infected mosquito in control group.ConclusionELISA data may be used as a surrogate for the MFA to evaluate transmission-blocking vaccine efficacy. This will facilitate the evaluation of transmission-blocking vaccines and implementation of this malaria control strategy.
Highlights
Mosquito stage malaria vaccines are designed to induce an immune response in the human host that will block the parasite's growth in the mosquito and block transmission of the parasite
Anti-Pfs25 monoclonal antibody 4B7 has potent transmission-blocking activity To study the relationship between antibody concentration and transmission-blocking activity for P. falciparum, the
Notwithstanding the limits of such a simple model, the results presented in this paper show that within the limits of the membrane-feeding assay (MFA), the reduction in the oocyst density per mosquito can be predicted from the concentration of anti-P25 antibody and that this reduction is largely independent of the species from which the antibody is derived, or from the formulation and adjuvants used to generate the antibody
Summary
Mosquito stage malaria vaccines are designed to induce an immune response in the human host that will block the parasite's growth in the mosquito and block transmission of the parasite. While multiple stages of the parasite life cycle are being targeted for vaccine development, vaccines against mosquito stage antigens are among the most novel. These mosquito-stage transmission-blocking (MSTB) vaccines are designed to prevent successful parasite infection of the mosquito vector and prevent further parasite spread among humans [3]. A different form of transmission-blocking vaccine, the RTS, S vaccine that blocks transmission of sporozoites from mosquitoes to humans, has recently demonstrated significant reduction in both uncomplicated and severe malaria in trials in Mozambique [5] and similar effects on both transmission and disease incidence have been widely observed with use of bed nets [6,7,8]. Transmission-blocking vaccines may prevent the spread of drug-resistant parasites or parasite mutants that have developed resistance to other malaria vaccines
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
