Mosquirix™ RTS,S Malaria Vaccine May 2023
GSK's Mosquirix™ RTS,S is a recombinant malaria vaccine with the P. falciparum circumsporozoite protein (CSP) from the pre-erythrocytic stage. RTS,S was created in 1987 by scientists working at GSK laboratories. 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.
In July 2015, the European Medicines Agency (EMA) gave a positive regulatory assessment of the RTS,S malaria vaccine for 5–17-month-olds. The EMA's Positive Opinion EMEA/H/W/002300/001 was last updated on July 31, 2020. The World Health Organization (WHO) recommends widespread use of the RTS,S/AS01 (RTS,S) malaria vaccine among children in sub-Saharan Africa.
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: 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. On April 19, 2023, The Lancet Infectious Disease published a Personal View that concluded that the claimed impact of the MVIP on mortality is not based on enough scientific evidence.
The WHO's malaria vaccine implementation program (MVIP) FAQs and the PATH Washington DC Overview. The U.S. CDC published Malaria Vaccines: The Way Forward on October 7, 2021. The WHO published a background paper. As of March 2022, this WHO position paper supersedes the 2016 publication, "Malaria vaccine: WHO position paper-2016. The WHO posted updated FAQs on April 21, 2022. GSK confirmed the WHO awarded prequalification to Mosquirix (RTS,S) on September 6, 2022. This is 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.
GlaxoSmithKline Biologicals S.A. 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 Availability 2023
As of May 2023, the Mosquirix (RTS,S) vaccine is available in African countries, including Malawi, Kenya, and Ghana. About 1.5 million African children have received the vaccine through a WHO-coordinated pilot program. About 2,000 cases of malaria are diagnosed in the United States annually, mostly in returned travelers, says the U.S. CDC. This vaccine is not available in the U.S.
Mosquirix History
GSK developed the RTS,S malaria vaccine for more than 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. This first-generation malaria vaccine demonstrates modest efficacy against malaria illness and holds promise as a public health tool, especially for children in high-transmission areas where mortality is high.
In partnership with PATH since 2001, GSK is currently testing the vaccine in Ghana, Kenya, and Malawi under the Malaria Vaccine Implementation Programme. Ministries of health are leading the implementation of the vaccine, which is being given to young children through the three countries' routine immunization programs, with WHO providing technical and scientific leadership, playing a coordinating role, and working in collaboration with GSK, PATH, and a range of other partners. The first dose of the vaccine has reached more than 500,000 children since the ministries of health initiated the three participating countries' pilots in 2019.
Mosquirix Indication
On 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. According to official recommendations in those areas, the Mosquirix vaccine should only be used in areas where malaria caused by Plasmodium falciparum is prevalent.
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 Dosage
Mosquirix is administered as an intramuscular injection. Phase 3 studies evaluated three and four doses. The WHO says the RTS,S malaria vaccine should be provided in a schedule of 4 doses in children from 5 months of age for the reduction of 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 Side Effects
With regard to vaccine safety, the RTS,S 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 that they can be safely included in future vaccination programs. The EMA published a Summary of the risk management plan for Mosquirix on July 31, 2020.
Mosquirix News: 2015 - 2022
March 28, 2023 - The WHO stated: Introducing the RTS,S malaria vaccine has resulted in a substantial reduction in 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 aimed at stopping the further 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 announced it is recommending widespread use of the RTS,S/AS01 (RTS,S) malaria vaccine among children in sub-Saharan Africa and in other regions with moderate to high P. falciparum malaria transmission.
September 9, 2021 - The NEJM journal published an ORIGINAL ARTICLE: Seasonal Malaria Vaccination with or without Seasonal Malaria Chemoprevention. CONCLUSIONS - Administration of RTS,S/AS01E was noninferior to chemoprevention in preventing uncomplicated malaria. The combination of 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, 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 'Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa. This trial is registered with ClinicalTrials.gov, number NCT00866619.
Mosquirix Clinical Trials
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 related to the nature of RTS,S vaccine efficacy in African adults that 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, 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, 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.
