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What should vaccine developers ask? Simulation of the effectiveness of malaria vaccines.

Penny MA, Maire N, Studer A, Schapira A, Smith TA - PLoS ONE (2008)

Bottom Line: Herd immunity effects can be achieved with even moderately effective (>20%) malaria vaccines (either PEV or BSV) when deployed through mass campaigns targeting all age-groups as well as EPI, and especially if combined with highly efficacious transmission-blocking components.We present for the first time a stochastic simulation approach to compare likely effects on morbidity, mortality and transmission of a range of malaria vaccines and vaccine combinations in realistic epidemiological and health systems settings.To test the validity and robustness of our conclusions there is a need for further modeling (and, of course, field research) using alternative formulations for both natural and vaccine induced immunity.

View Article: PubMed Central - PubMed

Affiliation: Swiss Tropical Institute, Basel, Switzerland.

ABSTRACT

Background: A number of different malaria vaccine candidates are currently in pre-clinical or clinical development. Even though they vary greatly in their characteristics, it is unlikely that any of them will provide long-lasting sterilizing immunity against the malaria parasite. There is great uncertainty about what the minimal vaccine profile should be before registration is worthwhile; how to allocate resources between different candidates with different profiles; which candidates to consider combining; and what deployment strategies to consider.

Methods and findings: We use previously published stochastic simulation models, calibrated against extensive epidemiological data, to make quantitative predictions of the population effects of malaria vaccines on malaria transmission, morbidity and mortality. The models are fitted and simulations obtained via volunteer computing. We consider a range of endemic malaria settings with deployment of vaccines via the Expanded program on immunization (EPI), with and without additional booster doses, and also via 5-yearly mass campaigns for a range of coverages. The simulation scenarios account for the dynamic effects of natural and vaccine induced immunity, for treatment of clinical episodes, and for births, ageing and deaths in the cohort. Simulated pre-erythrocytic vaccines have greatest benefits in low endemic settings (EIR of 84) PEV may lead to increased incidence of severe disease in the long term, if efficacy is moderate to low (<70%). Blood stage vaccines (BSV) are most useful in high transmission settings, and are comparable to PEV for low transmission settings. Combinations of PEV and BSV generally perform little better than the best of the contributing components. A minimum half-life of protection of 2-3 years appears to be a precondition for substantial epidemiological effects. Herd immunity effects can be achieved with even moderately effective (>20%) malaria vaccines (either PEV or BSV) when deployed through mass campaigns targeting all age-groups as well as EPI, and especially if combined with highly efficacious transmission-blocking components.

Conclusions: We present for the first time a stochastic simulation approach to compare likely effects on morbidity, mortality and transmission of a range of malaria vaccines and vaccine combinations in realistic epidemiological and health systems settings. The results raise several issues for vaccine clinical development, in particular appropriateness of vaccine types for different transmission settings; the need to assess transmission to the vector and duration of protection; and the importance of deployment additional to the EPI, which again may make the issue of number of doses required more critical. To test the validity and robustness of our conclusions there is a need for further modeling (and, of course, field research) using alternative formulations for both natural and vaccine induced immunity. Evaluation of alternative deployment strategies outside EPI needs to consider the operational implications of different approaches to mass vaccination.

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Related in: MedlinePlus

Time to elimination given initial efficacies (x-axis) of vaccine for different transmission settings (square indicates combination with MSTBV and circle without).All results are for vaccines delivered via EPI with mass vaccination, no elimination is achieved under these conditions for vaccines delivered via EPI or EPI with boosters. Results obtained assuming vaccine half-life of 10 years and homogeneity value of 10.
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pone-0003193-g003: Time to elimination given initial efficacies (x-axis) of vaccine for different transmission settings (square indicates combination with MSTBV and circle without).All results are for vaccines delivered via EPI with mass vaccination, no elimination is achieved under these conditions for vaccines delivered via EPI or EPI with boosters. Results obtained assuming vaccine half-life of 10 years and homogeneity value of 10.

Mentions: The time to elimination, dependent on initial vaccine efficacy, is considered in Figure 3, for those transmission settings and delivery modalities (mass vaccination at 95% coverage) where elimination was achieved within 20 years. Here, each vaccine has a half-life of 10 years and homogeneity value of 10. Combinations with MSTBV achieve elimination for lower initial efficacies of the other vaccine component and for a wider range of transmission settings than PEV or PEV with BSV. Interpretation of the time to elimination given the vaccine profile is difficult because of the discrete nature of the mass vaccination campaigns. In general, the time to elimination given this mass vaccination schedule does not strongly depend on the initial efficacy except at very high efficacy levels. In the lowest transmission settings with very high coverage and high initial efficacy of the MSTBV component, elimination is observed even with very low initial efficacies of the other components.


What should vaccine developers ask? Simulation of the effectiveness of malaria vaccines.

Penny MA, Maire N, Studer A, Schapira A, Smith TA - PLoS ONE (2008)

Time to elimination given initial efficacies (x-axis) of vaccine for different transmission settings (square indicates combination with MSTBV and circle without).All results are for vaccines delivered via EPI with mass vaccination, no elimination is achieved under these conditions for vaccines delivered via EPI or EPI with boosters. Results obtained assuming vaccine half-life of 10 years and homogeneity value of 10.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2527129&req=5

pone-0003193-g003: Time to elimination given initial efficacies (x-axis) of vaccine for different transmission settings (square indicates combination with MSTBV and circle without).All results are for vaccines delivered via EPI with mass vaccination, no elimination is achieved under these conditions for vaccines delivered via EPI or EPI with boosters. Results obtained assuming vaccine half-life of 10 years and homogeneity value of 10.
Mentions: The time to elimination, dependent on initial vaccine efficacy, is considered in Figure 3, for those transmission settings and delivery modalities (mass vaccination at 95% coverage) where elimination was achieved within 20 years. Here, each vaccine has a half-life of 10 years and homogeneity value of 10. Combinations with MSTBV achieve elimination for lower initial efficacies of the other vaccine component and for a wider range of transmission settings than PEV or PEV with BSV. Interpretation of the time to elimination given the vaccine profile is difficult because of the discrete nature of the mass vaccination campaigns. In general, the time to elimination given this mass vaccination schedule does not strongly depend on the initial efficacy except at very high efficacy levels. In the lowest transmission settings with very high coverage and high initial efficacy of the MSTBV component, elimination is observed even with very low initial efficacies of the other components.

Bottom Line: Herd immunity effects can be achieved with even moderately effective (>20%) malaria vaccines (either PEV or BSV) when deployed through mass campaigns targeting all age-groups as well as EPI, and especially if combined with highly efficacious transmission-blocking components.We present for the first time a stochastic simulation approach to compare likely effects on morbidity, mortality and transmission of a range of malaria vaccines and vaccine combinations in realistic epidemiological and health systems settings.To test the validity and robustness of our conclusions there is a need for further modeling (and, of course, field research) using alternative formulations for both natural and vaccine induced immunity.

View Article: PubMed Central - PubMed

Affiliation: Swiss Tropical Institute, Basel, Switzerland.

ABSTRACT

Background: A number of different malaria vaccine candidates are currently in pre-clinical or clinical development. Even though they vary greatly in their characteristics, it is unlikely that any of them will provide long-lasting sterilizing immunity against the malaria parasite. There is great uncertainty about what the minimal vaccine profile should be before registration is worthwhile; how to allocate resources between different candidates with different profiles; which candidates to consider combining; and what deployment strategies to consider.

Methods and findings: We use previously published stochastic simulation models, calibrated against extensive epidemiological data, to make quantitative predictions of the population effects of malaria vaccines on malaria transmission, morbidity and mortality. The models are fitted and simulations obtained via volunteer computing. We consider a range of endemic malaria settings with deployment of vaccines via the Expanded program on immunization (EPI), with and without additional booster doses, and also via 5-yearly mass campaigns for a range of coverages. The simulation scenarios account for the dynamic effects of natural and vaccine induced immunity, for treatment of clinical episodes, and for births, ageing and deaths in the cohort. Simulated pre-erythrocytic vaccines have greatest benefits in low endemic settings (EIR of 84) PEV may lead to increased incidence of severe disease in the long term, if efficacy is moderate to low (<70%). Blood stage vaccines (BSV) are most useful in high transmission settings, and are comparable to PEV for low transmission settings. Combinations of PEV and BSV generally perform little better than the best of the contributing components. A minimum half-life of protection of 2-3 years appears to be a precondition for substantial epidemiological effects. Herd immunity effects can be achieved with even moderately effective (>20%) malaria vaccines (either PEV or BSV) when deployed through mass campaigns targeting all age-groups as well as EPI, and especially if combined with highly efficacious transmission-blocking components.

Conclusions: We present for the first time a stochastic simulation approach to compare likely effects on morbidity, mortality and transmission of a range of malaria vaccines and vaccine combinations in realistic epidemiological and health systems settings. The results raise several issues for vaccine clinical development, in particular appropriateness of vaccine types for different transmission settings; the need to assess transmission to the vector and duration of protection; and the importance of deployment additional to the EPI, which again may make the issue of number of doses required more critical. To test the validity and robustness of our conclusions there is a need for further modeling (and, of course, field research) using alternative formulations for both natural and vaccine induced immunity. Evaluation of alternative deployment strategies outside EPI needs to consider the operational implications of different approaches to mass vaccination.

Show MeSH
Related in: MedlinePlus