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- - - MALARIA VACCINES

Saturday, 25th of May 2013

 

• MALARIA VACCINES 

Malaria continues to make a significant contribution to the global disease burden, with an estimated 660 000 deaths (range 490 000–836 000) in 2010. New tools are needed to combat the disease, as currently effective measures such as long-lasting insecticidal nets and artemisinin-based combination therapies are threatened by insecticide and drug resistance. There are currently several Plasmodium falciparum malaria vaccines in clinical trials, most of which are targeted at the pre-erythrocytic and blood stages of the parasite; there is only one P. vivax vaccine currently in clinical trials. The lead malaria vaccine candidate RTS,S/AS01 is being studied in a Phase III multi-centre efficacy trial conducted in 11 centres in 7 African countries. With over 12 months of follow-up post dose 3, the according-to-protocol vaccine efficacy against all clinical malaria episodes was estimated at 55.1% (95% CI, 50.5-59.2) in the 5–17 month age group and 33.0% (95% CI 26.4-38.9) in the 6–12 weeks age group. The Joint Technical Expert Committee (JTEG), which reports jointly to SAGE and the Malaria Policy Advisory Committee (MPAC), has reviewed available data from the Phase III trial for potential policy implications. There was a substantial difference between the efficacy results in the 2 age groups, though possibly confounded by transmission intensity and a differential contribution of cases from various sites between the age groups that could affect the overall efficacy estimates. Remaining questions include how efficacy changes with time since vaccination, transmission intensity, and seasonality, as well as the impact of co-administration with pentavalent vaccine, maternally acquired antibody, prior hepatitis B vaccination, and age or prior exposure to malaria. The lead malaria vaccine candidate will be evaluated as an addition to, and not as a replacement for existing preventive, diagnostic and treatment measures. Pending all data and analyses being available by 2015, and depending on the regulatory submission timings, malaria vaccine policy recommendations will be made in the last quarter of 2015 during a joint session of SAGE and MPAC.

SAGE was also updated on the Malaria Vaccine Technology Roadmap originally launched in 2006 and focused on P. falciparum, the under-5 year age group, and prevention of severe disease and death. Changing malaria epidemiology has rendered parts of the 2006 Roadmap out of date, and it is currently being revised. The updated version includes consideration of both P. falciparum and P. vivax. The updated strategic goals include both a focus on the traditionally targeted at-risk groups in endemic areas, and on transmission reduction that could enable elimination in multiple settings. Two sets of WHO Preferred Product Characteristics (PPCs) will be developed in 2013-2014 and will provide technical guidance for vaccine developers at early stages of vaccine research and development to address both of these strategic goals. Innovation is still greatly encouraged.

PPCs are not static exit criteria and will not replace standard policy or pre-qualification processes.

SAGE reaffirmed that malaria vaccine development remains a global imperative. SAGE recognized that countries will be under much political pressure to introduce a malaria vaccine when available. Because early results suggest that the vaccine is partially efficacious, and efficacy may differ by age group and transmission intensity, careful guidance from WHO will be essential so that countries can make appropriate decisions about introduction. SAGE strongly supported modeling and cost-effectiveness studies, which will have a critical role to play. SAGE recommended that in addition to the traditional parameters included in models, there be consideration of a potential interaction with different levels of use of existing preventive measures, and other factors that might alter vaccine efficacy. SAGE further suggested that consideration be given to analyses on the role of maternal antibody transfer, and nutritional and HIV status. SAGE strongly supported the extended follow-up of Phase III study participants as well as investigation of various immunization schedules, including a novel 6-month visit and consideration of use of  the 9-month visit. SAGE was very supportive of Phase IV studies, which are critical to determine the duration of protection and for pharmacovigilance. SAGE strongly acknowledged the need for ongoing malaria surveillance, noting the changes in epidemiology already occurring within regions and the possible impact of vaccination on the age pattern of morbidity, herd immunity, as well as the possible, unconfirmed relationship between transmission intensity and vaccine efficacy. SAGE emphasized the need to evaluate the acceptability of the vaccine and community communication strategies, given the partial efficacy of the vaccine, in order to avoid undermining confidence in all vaccines. SAGE strongly endorsed the early engagement between WHO and regulatory authorities regarding the lead malaria vaccine candidate, particularly with countries which may soon be asked to consider licensure of a malaria vaccine product. SAGE was encouraged by the interaction with the European Medicines Agency and would support a flexible approach when the agency reviews the product, to include consideration of the public health impact as part of the evaluation. SAGE noted the utility of PPCs to developers and funders, and proposed that the opportunity for input into future PPCs at an early stage for any vaccine of public health importance could be included as part of SAGEs global public health mandate.