Q&A on the malaria vaccine implementation programme (MVIP)
- What is RTS,S/AS01?
- What makes RTS,S different from malaria vaccine candidates currently under development?
- What is the efficacy of the RTS,S vaccine?
- What is WHO’s official position on RTS,S?
- What is the purpose of the malaria vaccine implementation programme?
- Which countries will participate in MVIP?
- What were the criteria for country selection?
- Who will be eligible for vaccination?
- When will the vaccinations begin?
- Is the vaccine safe?
- Are there any known side effects?
- Who developed and who manufactures the vaccine?
- What is the purpose of the Phase 4 studies, and how do they relate to the MVIP?
- Which partners are involved in MVIP?
- Who will fund MVIP?
- What is the expected duration of the programme?
- Why is the MVIP being rolled out only in Africa, and not in other regions?
- What other interventions exist for malaria control?
- Is RTS,S licensed by a regulatory authority?
1. What is RTS,S/AS01?
RTS,S/AS01 (RTS,S) – also known as Mosquirix™ – is an injectable vaccine that provides partial protection against malaria in young children. The vaccine acts against Plasmodium falciparum, the most deadly malaria parasite globally and the most prevalent in Africa.1 It is being evaluated in sub-Saharan Africa as a complementary malaria control tool that potentially could be added to (and not replace) the core package of WHO-recommended preventive, diagnostic and treatment measures.
2. What makes RTS,S different from malaria vaccine candidates currently under development?
RTS,S is the first and, to date, the only vaccine to show a protective effect against malaria among young children in Phase 3 clinical trials. Beginning in 2018, it will be the first malaria vaccine provided to young children through routine immunization programmes. Three sub-Saharan African countries will introduce the vaccine in selected areas as part of a large-scale pilot implementation programme.
3. What is the efficacy of the RTS,S vaccine?
The Phase 3 trial, conducted over 5 years (from 2009 to 2014), enrolled approximately 15 000 young children and infants in 7 sub-Saharan African countries.2 The trial sites within these countries represented a range of malaria transmission settings. Among children aged 5–17 months who received 4 doses of RTS,S, the vaccine prevented approximately 4 in 10 cases of malaria. Vaccine efficacy against severe malaria3 in this age group was 31.5%, with significant reductions seen in overall hospital admissions as well as in admissions due to malaria or severe anaemia. A 28% reduction in blood transfusions, required to treat life-threatening malaria anemia, was also seen.
4. What is WHO’s official position on RTS,S?
In October 2015, after a thorough review of the Phase 3 trial results, two independent WHO advisory groups –the Strategic Advisory Group of Experts (SAGE) on Immunization and the Malaria Policy Advisory Group (MPAC) – jointly called for pilot implementation of the vaccine in 3 to 5 settings in sub-Saharan Africa. The vaccine was recommended for use in the pilot implementation programme, with the first dose given to children soon after the age of 5 months.
In a position paper published on 29 January 2016, WHO officially adopted the joint recommendation of SAGE and MPAC; in doing so, the Organization recognized the public health potential of the RTS,S vaccine while also acknowledging the need for further evaluation before considering wide-scale deployment. There is currently no WHO policy recommendation for the large-scale use of the RTS,S malaria vaccine beyond the pilot programme.
5. What is the purpose of the malaria vaccine implementation programme?
The efficacy of the RTS,S vaccine was established in the Phase 3 clinical trials (see #3, above); children who receive 4 doses of the vaccine have a significantly lower risk of developing clinical malaria and severe malaria. The malaria vaccine implementation programme (MVIP), coordinated by WHO, has been designed to address several outstanding questions related to the public health use of the vaccine.
Specifically, the MVIP will assess the operational feasibility of administering the required 4 doses of the vaccine in children; the vaccine’s potential role in reducing childhood deaths; and its safety in the context of routine use.
6. Which countries will participate in MVIP?
Ghana, Kenya and Malawi will introduce RTS,S in selected areas as part of the MVIP. Countries selected for the programme were officially announced by WHO on 24 April 2017. Each of the 3 countries will select the districts and regions to be included in the pilots.
7. What were the criteria for country selection?
In December 2015, WHO issued a call for expressions of interest from African Ministries of Health to collaborate in the malaria vaccine implementation programme. Of the 10 countries that responded positively, 3 were selected for the programme based on pre-specified criteria. Key among these was the desire to engage in the MVIP by national stakeholders – particularly the Ministry of Health – and well-functioning malaria and immunization programmes.
Other criteria included: good coverage of recommended malaria control interventions and childhood vaccinations; moderate-to-high malaria transmission despite good implementation of WHO-recommended malaria interventions; a sufficient number of infants living in the malaria-transmission areas where the vaccine will be introduced; strong implementation research or evaluation experience in the country; and capacity to assess safety outcomes. Participation in the Phase 3 RTS,S trial was an additional criterion considered during the country selection process.
8. Who will be eligible for vaccination?
The vaccine will be made available to young children living in selected areas in Ghana, Kenya and Malawi through routine immunization programmes. At least 360 000 children in the selected areas will be vaccinated across all 3 countries. Some regions selected for participation in the MVIP will serve as comparator areas in which the vaccine will not be available initially.
Immunization authorities in the 3 countries will specify the exact vaccination schedule, based on WHO recommendations. A 4-dose schedule is required, with the first dose given as soon as possible after 5 months of age followed by doses 2 and 3 at approximately monthly intervals and the fourth dose near the child’s second birthday. The vaccine will not be available in all regions of each pilot country, nor will it be given to adults or children outside the target age group.
9. When will the vaccinations begin?
A great deal of preparatory work is required before the RTS,S vaccinations can begin. WHO and partners are engaged in intensive discussions with stakeholders in the selected countries to plan for the vaccine introduction and evaluations. Vaccinations are due to begin in mid-2018.
10. Is the vaccine safe?
In the Phase 3 trial, the vaccine was generally well tolerated, with adverse reactions similar to those of other childhood vaccines. The European Medicines Agency (EMA), a stringent medicines regulatory authority, carried out a scientific assessment of RTS,S and concluded that the vaccine has an acceptable safety profile in a scientific opinion issued in July 2015. As with other new vaccines, and in line with national regulations, the safety profile for RTS,S will be monitored closely as the vaccine becomes more widely available.
11. Are there any known side effects?
Known side effects include pain and swelling in the limb where the vaccine is injected, and fever. These side effects are similar to reactions observed with other vaccines given to children. Occasionally, children with fever have seizures. An increased risk of febrile seizures was seen within 7 days of the administration of any of the RTS,S vaccine doses. In the phase 3 trial, children who had febrile seizures after vaccination recovered completely and there were no long-lasting consequences.
12. Who developed and who manufactures the vaccine?
GSK led the development of RTS,S over a 30-year period. In 2001, GSK began collaborating with the PATH Malaria Vaccine Initiative (MVI) to continue developing RTS,S. A 5-year Phase 3 efficacy and safety trial was conducted between 2009 and 2014 through a partnership that involved GSK, MVI (with support from the Bill & Melinda Gates Foundation), and a network of African research centres at 11 sites in 7 countries. GSK is the vaccine manufacturer.
13. What is the purpose of the Phase 4 studies, and how do they relate to the MVIP?
As part of the MVIP, GSK is conducting a number of Phase 4 studies in regions where the RTS,S vaccine will be deployed. These studies – routine practice after a vaccine is licensed for use – will gather additional information on the vaccine’s effectiveness and on any side effects associated with its long-term use. Data collected through the Phase 4 studies will complement data from the pilot evaluations led by WHO.
14. Which partners are involved in MVIP?
The MVIP is coordinated and led by WHO in close collaboration with Ministries of Health in participating countries and a range of in-country and international partners. In each country, the Ministry of Health will deliver the malaria vaccine through its national immunization programme in the selected areas and regions. National malaria control programmes will ensure that existing WHO-recommended prevention tools, such as long-lasting insecticidal nets (LLINs) and artemisinin-based combination therapies (ACTs), continue to be deployed on a wide scale. In-country research partners will be identified in the coming months to lead a rigorous evaluation of the RTS,S vaccine implementation.4
WHO will continue to work in partnership with PATH across a number of areas, including on economic assessments, pharmacovigilance, and in the qualitative assessment of behaviour change that may occur during the introduction of the vaccine. GSK will continue to play a key role in manufacturing the vaccine and supplying it free of charge to the MVIP. As the programme progresses, WHO expects other partners to become involved.
15. Who will fund MVIP?
In November 2016, WHO announced that funding for the first phase of the MVIP had been mobilized from Gavi, the Vaccine Alliance, The Global Fund to Fight AIDS, Tuberculosis and Malaria and UNITAID.
16. What is the expected duration of the programme?
The first phase of the programme (2017–2020) will provide initial insights on the programmatic feasibility of delivering the vaccine in real-life settings and on the safety profile of RTS,S in the context of routine use. The second phase of the MVIP (2021–2022) will continue to monitor feasibility and safety while also generating results on the vaccine’s impact on child survival. Taken together, these results will help inform future decisions on the wider-scale deployment of the vaccine.
17. Why is the MVIP being rolled out only in Africa, and not in other regions?
The WHO African region bears the greatest burden of malaria worldwide. Most malaria illness and deaths in this region are caused by the parasite targeted by the RTS,S vaccine (P. falciparum). In recent years, malaria death rates in the region have dropped significantly following a major scale-up of LLINs, ACTs and other malaria control measures. However, the disease continues to take a heavy toll: in 2015, there were an estimated 394 000 malaria deaths in the region, mainly among young children. 5 The RTS,S malaria vaccine was developed for use in Africa and for African children. Additional studies will be needed before the vaccine can be recommended for use outside Africa.
18. What other interventions exist for malaria control?
Existing WHO-recommended interventions for malaria control include: LLINs, indoor residual spraying with insecticides, preventive treatment for infants and during pregnancy, prompt diagnostic testing, and treatment of confirmed cases with effective anti-malarial medicines. In the Sahel, a sub-Saharan region of Africa, seasonal malaria chemoprevention is recommended in areas with highly seasonal malaria transmission. Deployment of these tools has already dramatically lowered the malaria disease burden in many African settings. The disease burden can be further lowered through the continued scale-up of these existing control measures.
While efforts to sustain and further expand existing interventions must continue, new complementary tools and strategies are needed in some areas to accelerate the fight against malaria and further drive down the disease burden. The malaria vaccine is proposed as a potential additional tool to complement the existing package of WHO-recommended preventive, diagnostic and treatment measures for malaria.
19. Is RTS,S licensed by a regulatory authority?
The European Medicines Agency (EMA) carried out a scientific assessment of RTS,S and issued a “European scientific opinion” on the vaccine in July 2015. This opinion was given as part of the EMA’s cooperation with WHO, whereby EMA provides opinions on medicines that are not intended for use in the European Union but are needed to prevent or treat diseases of major public health importance around the world. The opinion indicated that, in EMA’s assessment, the quality of the vaccine and its risk-benefit profile are favorable from a regulatory perspective. EMA’s opinion did not consider contextual elements such as the feasibility of implementation, the value of the vaccine in the context of other malaria control measures, and the likely cost-effectiveness of the intervention in different settings. RTS,S is expected to be approved by the National Regulatory Authorities (NRAs) in each of the three countries participating in the MVIP for use in the context of the pilots.
1. The vaccine offers no protection against P. vivax malaria, which predominates in many countries outside of Africa.
2. These countries included: Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique, and the United Republic of Tanzania.
3. Severe malaria refers to those cases where the initial infection with the malaria parasite evolves into an acute, life-threatening illness.
4. Specifically, they will evaluate the feasibility of delivering the vaccine in real-life settings, the impact of the vaccine on childhood survival and the vaccine’s safety profile in the context of routine use.
5. In 2015, malaria killed an estimated 303 000 under-fives globally, including 292 000 in the WHO African Region.