Mosquirix™ (RTS,S) Malaria Vaccine
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, and scientific information was updated 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 on 25-29 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.
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 in 2023, sufficient data on safety and efficacy have been collected to allow for a broader recommendation for using the RTS,S/AS01 vaccine. 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.
The WHO's 2023 World Malaria Report estimated 249 million malaria cases globally in 20222.
GlaxoSmithKline Biologicals S.A. was created in 1987 by scientists working at GSK laboratories - Mosquirix H-W-2300. GSK's commitment to people at risk of malaria is linked. GSK is a science-led global healthcare company with a particular purpose: to help people do more, feel better, and live longer. For further information, please visit GSK.
Mosquirix RTS,S/AS01 Vaccine Availability 2023
As of November 2023, the Mosquirix (RTS,S) vaccine is available in African countries, including Malawi, Kenya, and Ghana. About 18 African countries are set to receive 18 million doses over the next two years. 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 RTS,S/AS01 malaria vaccine is not available in the U.S.
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
November 22, 2023 - "This could be a real game-changer in our fight against malaria," said UNICEF Executive Director Catherine Russell. "Introducing vaccines is like adding a star player to the pitch. With this long-anticipated step, spearheaded by African leaders, we are entering a new era in immunization and malaria control, hopefully saving the lives of hundreds of thousands of children every year."
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-drug combination, and also used bednets likely had greater than 90% protection against malaria episodes during the study."
July 5, 2023 - GAVI, UNICEF, and WHO announced that 12 countries across different African regions are set to receive 18 million doses of the first-ever malaria vaccine over the next two years.
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.
October 29, 2022 - The WHO expressed serious concerns about malaria cases in Ethiopia's northern regions.
October 10, 2022 - Malawi's health ministry says it will soon roll out the RTS, S vaccine for children under age five.
September 29, 2022 - A new WHO-produced brochure describes an initiative to stop the spread of An. stephensi in Africa
September 6, 2022 - Thomas Breuer, Chief Global Health Officer, GSK, said: "WHO prequalification of Mosquirix is a key step in reaching children with the first and only approved malaria vaccine.
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.
December 6, 2021 - The WHO welcomed the Gavi Alliance Board's investment in the first malaria vaccine program.
October 6, 2021 - The World Health Organization 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.
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.
March 12, 2021 - Review: Towards Eradication of Malaria: Is the WHO's RTS, S/AS01 Vaccination Effective Enough?
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. However, Mosquirix does not offer complete protection against malaria caused by P. falciparum, says the U.S. Centers for Disease Control and Prevention (CDC). The NEJM published the results of a phase 3 clinical study sponsored by the London School of Hygiene and Tropical Medicine on September 9, 2021 that concluded 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, leading to a state of 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.