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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

Effect of PEV (a,c,e) and BSV (b,d,f) on infectivity to vector over 20 years when delivered via EPI (black), EPI with boosters (blue) and EPI with 95% mass vaccination (red) for transmissions settings of EIR 5.25 (a,b), 21 (c,d) and 168 (e,f).Results obtained assuming a vaccine efficacy of 80%, half-life of 10 years and homogeneity value of 10. Note that the blue and black lines almost overlap.
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pone-0003193-g001: Effect of PEV (a,c,e) and BSV (b,d,f) on infectivity to vector over 20 years when delivered via EPI (black), EPI with boosters (blue) and EPI with 95% mass vaccination (red) for transmissions settings of EIR 5.25 (a,b), 21 (c,d) and 168 (e,f).Results obtained assuming a vaccine efficacy of 80%, half-life of 10 years and homogeneity value of 10. Note that the blue and black lines almost overlap.

Mentions: In line with our previous simulations, we find that moderately efficacious pre-erythrocytic vaccines applied via EPI do not have any substantial effect on malaria transmission, (results not shown), because only a small proportion of the population is protected. If the initial efficacy of PEV is high then effects on transmission are observed for EPI and EPI with boosters (Figure 1a, c, e). If a high efficacy PEV is delivered via EPI with mass vaccination with high coverage, herd immunity with substantial transmission effects are achieved (Figure 1a, c, e).


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)

Effect of PEV (a,c,e) and BSV (b,d,f) on infectivity to vector over 20 years when delivered via EPI (black), EPI with boosters (blue) and EPI with 95% mass vaccination (red) for transmissions settings of EIR 5.25 (a,b), 21 (c,d) and 168 (e,f).Results obtained assuming a vaccine efficacy of 80%, half-life of 10 years and homogeneity value of 10. Note that the blue and black lines almost overlap.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0003193-g001: Effect of PEV (a,c,e) and BSV (b,d,f) on infectivity to vector over 20 years when delivered via EPI (black), EPI with boosters (blue) and EPI with 95% mass vaccination (red) for transmissions settings of EIR 5.25 (a,b), 21 (c,d) and 168 (e,f).Results obtained assuming a vaccine efficacy of 80%, half-life of 10 years and homogeneity value of 10. Note that the blue and black lines almost overlap.
Mentions: In line with our previous simulations, we find that moderately efficacious pre-erythrocytic vaccines applied via EPI do not have any substantial effect on malaria transmission, (results not shown), because only a small proportion of the population is protected. If the initial efficacy of PEV is high then effects on transmission are observed for EPI and EPI with boosters (Figure 1a, c, e). If a high efficacy PEV is delivered via EPI with mass vaccination with high coverage, herd immunity with substantial transmission effects are achieved (Figure 1a, c, e).

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