Immunization, Vaccines and Biologicals

Most advanced malaria vaccine candidate and timing for policy recommendations

The most advanced malaria vaccine candidate, RTS,S/AS01, is progressing through a pivotal Phase 3 trial, and may be licensed in the future. Contingent on the completion of the ongoing phase 3 trial and submission of data supportive of use, WHO will review the evidence for policy recommendation in 2015.

The recommendations on RTS,S/AS01 will consider its potential as an addition in some settings to existing preventive measures, such as long-lasting insecticidal nets and indoor residual spraying. The priority need for high quality artemisinin-combination treatments should continue regardless of availability and use of RTS,S vaccine. Based on currently available data the vaccine will be a likely addition to, not a replacement for, existing preventive and treatment measures.

Results of a phase 2 trial of RTS,S/AS01 in Kenya are encouraging, with the vaccine showing 51% efficacy in reducing all episodes of clinical malaria in infants aged 5-17 months over 15 months. There are few published data on clinical efficacy when administered to the target population i.e. infants at 6-14 weeks of age, with RTS,S/AS01 administered together with vaccines in the routine immunization schedule. The vaccine candidate is being developed under a collaboration between GlaxoSmithKline and the PATH Malaria Vaccine Initiative (MVI), with funding from the Bill & Melinda Gates Foundation to MVI.

Phase 3 Trial of RTS,S/AS01

The Phase 3 trial, which started in May 2009, has completed enrollment with 15 460 children in the following seven countries in sub-Saharan Africa: Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique, and the United Republic of Tanzania. The children are in two age groups: 1) children aged 5-17 months at first immunization, receiving RTS,S/AS01 without co-administration of other vaccines; and 2) infants of 6-12 weeks at first immunization in co-administration with pentavalent vaccines in the routine immunization schedule.

Timing for policy recommendations

Before any malaria vaccine can be introduced in a national immunization programme, it must receive marketing authorization by the competent regulatory authority and be granted national registration in the countries in which it is to be used. In the case of RTS,S/AS01, the first regulatory step would be a positive scientific opinion from the European Medicines Agency, which will assess it according to standards necessary for a marketing authorization. Based on WHO's experience of deployment of other vaccines in young infants in sub-Saharan Africa, the following steps tend to occur before widespread implementation: WHO policy recommendation on use and WHO prequalification. These are followed by a national policy decision to introduce the vaccine in individual countries. WHO anticipates that the RTS,S/AS01 vaccine, if approved for large scale use in malaria endemic countries, will be considered for the 6-14 week age group for co-administration together with other vaccines as part of routine childhood immunization schedules.

The process of developing policy recommendations

As part of the WHO policy process, the immunization and malaria departments jointly convened a Joint Technical Expert Group (JTEG) on Malaria Vaccines in June 2009. JTEG determined that there should be sufficient data available to make a draft policy recommendation regarding RTS,S/AS01 in 2015 for subsequent consideration by the WHO Strategic Advisory Group of Experts (SAGE) on immunization, the principal advisory group to WHO for vaccines and immunization. The WHO policy recommendation will take into consideration safety and efficacy results from the current phase 3 trial after 30-month follow-up of children receiving the malaria vaccine together with vaccines in the routine immunization schedule, as well as site-specific data on efficacy and impact on severe malaria. The JTEG and SAGE will carefully evaluate the potential additional public health value of RTS,S/AS01 when combined with existing malaria control measures, such as vector control, intermittent preventive treatment, and prompt diagnosis and case management of malaria.

The first interim set of data from the phase 3 trial became available in October 2011. The efficacy figure was 55% reduction in frequency of malaria episodes during the 12 months of follow-up in children 5-17 months of age at first immunization. This is not the vaccine development partnership's stated target population, which is children aged 6-14 weeks of age, in co-administration with other vaccines. The efficacy in this target population is not yet known.

A second interim set of data is expected in late 2012, with the final, full data package expected in late 2014. WHO will convene JTEG to review each interim set of data.

Licensure as a hepatitis B vaccine

The active principle in the RTS,S/AS01 vaccine is a fusion protein between a malaria antigen and hepatitis B surface antigen, using a new and potent adjuvant. RTS,S/AS01 will likely be submitted for licensure as a joint malaria and hepatitis B vaccine.

Other malaria vaccines

Other vaccines with higher efficacy are desirable. Several promising vaccine candidates are currently being studied, but are at least 5-10 years behind RTS,S/AS01 in their development.

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Last updated: 9 November 2011

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