Mosquirix™ (RTS,S) Malaria Vaccine Clinical Trials, Dosage, Efficacy, Indication, Side Effects
GSK's Mosquirix™ RTS, S/AS01 (RTS,S) is a recombinant malaria vaccine with the P. falciparum circumsporozoite protein (CSP) from the pre-erythrocytic stage. Mosquirix triggers the immune system to defend against the first stages when the Plasmodium falciparum malaria parasite enters the human host's bloodstream through a mosquito bite and infects liver cells. The T-cell epitope of CSP is O-fucosylated in Plasmodium falciparum and Plasmodium vivax, while the RTS,S malaria vaccine produced in yeast is not. The vaccine prevents the parasite from infecting the liver, entering the bloodstream, infecting red blood cells, and leading to disease symptoms. In addition, because of the vaccine's composition, it also protects against the hepatitis B virus, but should not be used only for this purpose.
In July 2015, the European Medicines Agency (EMA) issued a positive regulatory assessment EMEA/H/W/002300/001 of the RTS,S malaria vaccine for 5–17-month-olds, which was updated on July 31, 2020. The EMA updated scientific information in July 2023. The EMA stated that this malaria vaccine should be used in areas where malaria is caused by Plasmodium falciparum.
The World Health Organization (WHO) and Malaria Policy Advisory Group (MPAG) recommend widespread use of the RTS, S/AS01 malaria vaccine among children in sub-Saharan Africa. GSK confirmed the WHO awarded prequalification to Mosquirix (RTS,S) on September 6, 2022, the first WHO prequalification for a malaria vaccine. The WHO prequalification is a mandatory prerequisite for United Nations agencies, such as UNICEF, to procure the vaccine in partnership with Gavi, the Vaccine Alliance, and eligible countries. The WHO announced the World Malaria Report 2022 on December 8, 2022. In March 2022, a new WHO position paper was published. The WHO posted updated FAQs in July 2023. The WHO's Strategic Advisory Group of Experts (SAGE) updated malaria vaccine recommendations in September 2023. About 1.5 million African children have received the vaccine through a WHO-coordinated pilot program.
On August 22, 2023, The Lancet Infectious Diseases published a study that confirms the benefits of combining the RTS,S/AS01E vaccine with antimalarial drugs (sulfadoxine, pyrimethamine, and amodiaquine) to reduce clinical malaria episodes, including cases of severe malaria, and deaths from malaria in young children by nearly two-thirds compared with either RTS,S vaccination or seasonal malaria chemoprevention alone. In April 2024, The Lancet published results from a study and related editorial: In the first two years of implementation of RTS,S, the three primary doses were effectively deployed in three African countries. No evidence of safety was observed in the phase 3 trial, and the introduction of the vaccine was associated with substantial reductions in hospital admissions with severe malaria. On May 6, 2024, The Lancet published results from a phase 3 study that concluded all tested dosing regimens. Improved vaccine efficacy in participants infected during vaccination could suggest new strategies for highly efficacious malaria vaccine development and implementation.
In November 2023, Gavi reported data from the evaluation of the pilot introduction of the RTS, S/AS01 malaria vaccine, which shows a 13% reduced mortality from all causes in children eligible for vaccination. The RTS/S vaccine was also responsible for a 22% reduction in hospitalization for severe clinical malaria.
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Mosquirix RTS,S/AS01 Vaccine Availability 2024
As of May 24, 2024, over 4.3 million doses of RTS,S have been delivered to 8 African countries, including Cameroon, Malawi, Kenya, Sierra Leone, and Ghana. On January 23, 2024, 1of the RTS,S malaria doses vaccine arrived in Liberia. On January 22, 2024, Cameroon became the first country to include the RTS,S malaria vaccine into its routine national immunization services outside the malaria vaccine pilot program. About 18 African countries are set to receive 18 million doses over the next two years. On December 16, 2023, Sierra Leone received 550,000 doses of Mosqurix. On November 22, 2023, about 330,000 RTS,S malaria vaccine doses arrived in Cameroon. Mosquirix allocations (July 2023) were also made for new introductions in Benin, Burkina Faso, Burundi, Cameroon, the Democratic Republic of the Congo, Liberia, Niger, Sierra Leone, and Uganda. The Mosquirix malaria vaccine is not available in the U.S.
Mosquirix RTS,S/AS01 Vaccine United States
The U.S. Centers for Disease Control and Prevention (CDC) published Malaria Vaccines: The Way Forward on October 7, 2021, collaborating with the Kenya Medical Research Institute. The CDC led the RTS,S/AS01 clinical trial at one site in western Kenya. While the studies are ongoing, sufficient data on safety and efficacy have been collected to allow for a broader recommendation for using the RTS,S/AS01 vaccine.
Mosquirix RTS,S/AS01 Vaccine History
GSK developed the RTS,S malaria vaccine over 30 years. The RTS,S vaccine was created in 1987 as part of a collaboration between GlaxoSmithKline and the Walter Reed Army Institute of Research that began in 1984.
Mosquirix RTS,S/AS01 Vaccine Indication
On October 6, 2020, the WHO recommended widespread use of the RTS,S/AS01 (RTS,S) malaria vaccine among children in sub-Saharan Africa and other regions with moderate to high P. falciparum malaria transmission. In Europe, Mosquirix is currently indicated for children aged 5 to 17 months and infants aged 6 to 12 weeks at the first vaccination time to help protect against malaria caused by the parasite Plasmodium falciparum. However, Mosquirix is not approved for older children, teens, or adults.
Mosquirix RTS,S/AS01 Dosage
Mosquirix is administered as an intramuscular injection. The WHO says the RTS,S malaria vaccine should be provided in 4 doses in children from 5 months of age to reduce malaria disease and burden. On March 28, 2023, the WHO stated the SAGE recommends flexibility in the immunization schedule and supports reducing the minimum interval between doses 3 and 4 to 6 months to optimize impact.
Mosquirix RTS,S/AS01 Side Effects
The RTS,S/AS01 vaccine safety profile is similar to other routine vaccines given to children except for an increased risk of febrile seizures. At first vaccination, children aged 5–17 months were more likely than controls to have a febrile seizure within seven days after vaccination, especially during the third dose. This effect was transient, and all affected children recovered after seven days. Safety surveillance also suggested a potential increased risk of meningitis and cerebral malaria in this same age group.27 A study in Kenyan children with WHO Stage 1 or 2 HIV disease found that RTS,S/AS01 was well-tolerated in this population and can be safely included in future vaccination programs. The EMA published a Summary of the risk management plan for Mosquirix on July 31, 2020.
RTS, S/AS01E Vaccination with Malaria Chemoprevention
A study published in The Lancet Infectious Diseases in August 2023 confirms that the benefits of combining the RTS, S/AS01E (RTS,S) malaria vaccine with antimalarial drugs (sulphadoxine-pyrimethamine and amodiaquine) reduced clinical malaria episodes, including cases of severe malaria and deaths from malaria in young children by nearly two-thirds (57·7% (53·3 to 61·7) and versus RTS/AS01E-alone being 59·0% (54·7 to 62·8) compared with either RTS, S vaccination or seasonal malaria chemoprevention alone.
Mosquirix RTS, S/AS01 News
May 6, 2024—The Lancet published a commentary on asymptomatic parasitemia and RTS,S vaccine efficacy. Genotyping did indicate that RTS,S is able to block infections before the parasite can reach the blood stage. Notably, there was no difference in protective efficacy with head-to-head comparisons of RTS,S dosing regimens.
January 9, 2024 - "The selected vaccine, Mosquirix RTS, has been chosen by the country (Cameroon) based on its prequalification, ensuring guaranteed quality, efficacy, and safety for its inclusion in the vaccination programs."
August 22, 2023 - LSHTM Professor Brian Greenwood, MD, a member of the research team, said, "In addition to the study's findings—which by themselves are remarkable—we can say that children who received the RTS,S combination, and also used bednets likely had greater than 90% protection against malaria episodes during the study."
March 28, 2023 - The WHO stated: Introducing the RTS, S malaria vaccine has substantially reduced severe malaria and all-cause mortality among age-eligible children.
April 21, 2022 - The WHO announced more than 1 million children in Ghana, Kenya, and Malawi have received one or more doses of the RTS, S/AS01 (RTS, S) vaccine.
September 9, 2021 - The NEJM journal published an ORIGINAL ARTICLE - Administration of RTS, S/AS01E was noninferior to chemoprevention in preventing uncomplicated malaria. Combining these interventions resulted in a substantially lower incidence of uncomplicated malaria, severe malaria, and death from malaria than either intervention alone.
January 27, 2021 - GSK, PATH, and Bharat Biotech (BBIL) announced a product transfer agreement for the malaria vaccine, RTS, S/AS01E. In addition, GSK will retain the adjuvant's production (AS01E) and supply it to BBIL.
August 23, 2017 - Original Research was published. In conclusion, the RTS, S/AS01E vaccine induces T cells of higher functional heterogeneity and polyfunctionality than previously characterized. Responses detected in memory CD4+ T cell compartments may provide correlates of RTS, S/AS01-induced immunity, and duration of protection in future correlates of immunity studies.
April 23, 2015 - The Lancet published 'The efficacy and safety of RTS, S/AS01 malaria vaccine with or without a booster dose in African infants and children. This trial is registered with ClinicalTrials.gov, number NCT00866619.
Mosquirix Clinical Trials
The Phase III efficacy and safety trial of RTS, S showed that the vaccine candidate could provide meaningful public health benefits by reducing the burden of malaria.
The Lancet published results from a study in April 2024, among children eligible to have received at least one dose of RTS,S, there was no evidence of an excess of meningitis or cerebral malaria cases in implementation areas compared with comparison areas (hospital admission with meningitis: IRR 0·63 [95% CI 0·22–1·79]; hospital admission with cerebral malaria: IRR 1·03 [95% CI 0·61–1·74]).
The NEJM published the results of phase 3 clinical study sponsored by the London School of Hygiene and Tropical Medicine on September 9, 2021, which concluded that the administration of RTS, S was noninferior to chemoprevention in preventing uncomplicated malaria. However, combining these interventions resulted in a substantially lower incidence of uncomplicated malaria, severe malaria, and death from malaria than either intervention alone.
Clinical Trial NCT03806465: An Evaluation of the Cluster-randomised Pilot Implementation of RTS, S/AS01 Through Routine Health Systems in Moderate to High Malaria Transmission Settings in Africa.
Clinical Trial: NCT04661579: The proposed trial design has been developed to answer several questions about nature. These S vaccine efficacy in African adults may be influenced by concurrent and/or past P. falciparum infection and late immunologic hypo-responsiveness. The proposed study design encompasses five groups. Three groups (Groups 1, 2, and 3) will be administered RTS, S/AS01E on a 0, 1, and 7-month schedule with Dose 3 delivered as a 1/5th fractional dose. Two groups (Groups 4 and 5) will be administered a comparator vaccine on a 0, 1, and 7-month schedule.
Clinical Trial NCT03143218: A double-blind, individual randomized phase 3 trial will be undertaken in 6000 children under the age of five years living in areas of Burkina Faso or Mali where the transmission of malaria is intense and highly seasonal to determine whether the malaria vaccine RTS, S/AS01 is (a) as effective as SMC with SP + AQ in preventing clinical malaria (b) provides additional, useful protection when given together with SMC. The primary trial end-point will be the incidence of clinical episodes of malaria detected by passive case detection. The protective efficacy of the combination as compared with the vaccine alone against these outcomes was 59.6% (95% CI, 54.7 to 64.0), 70.6% (95% CI, 42.3 to 85.0), and 75.3% (95% CI, 12.5 to 93.0), respectively.
