Mosquirix™ RTS,S/AS01 (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. 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/AS01 malaria vaccine produced in yeast is not.
In July 2015, the European Medicines Agency (EMA) gave a positive regulatory assessment of the RTS,S/AS01e 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 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 provide complete protection against malaria caused by P. falciparum, says the U.S. CDC. The malaria vaccine is designed to prevent 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.
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/AS01 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 October 6, 2021, the WHO Director-General, Dr. Tedros Adhanom Ghebreyesus, announced that the WHO recommends the RTS,S/AS01 malaria vaccine be used to prevent P. falciparum malaria in children living in regions with moderate to high transmission as defined by WHO. Furthermore, on March 4, 2022, the WHO published an updated position paper on the RTS,S/AS01 malaria vaccine that includes the October 2021 recommendation calling for the wider use of the vaccine among children living in areas of moderate-to-high P. falciparum malaria transmission. The paper complements the recent addition of advice to the WHO Guidelines for malaria.
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/AS01) 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.
As of December 2022, the Mosquirix (RTS,S/AS01) vaccine is available in the African countries of Malawi, Kenya, and Ghana and received WHO PreQualification on September 6, 2022. However, the U.S. FDA has not approved this malaria vaccine.
The RTS,S/AS01 malaria vaccine, was developed by GSK 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. The primary evidence derives from a large clinical trial conducted in seven African countries (Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique, and Tanzania), reports the EMA. This trial showed that Mosquirix provides modest protection against Plasmodium falciparum malaria in children 12 months following vaccination. In addition, the vaccine effectively prevented a first or only clinical malaria episode in 56% of children aged between 5 and 17 months and 31% of children aged 6-12 weeks.
WHO certification of malaria elimination, 1955–2021: Countries with at least three consecutive years of zero indigenous cases are eligible to apply for a WHO certification of malaria-free status. Since January 1, 2019, Burundi's Ministry of Health has reported nearly 6 million malaria cases (out of a population of approximately 12 million), with more than 1,800 deaths.
GSK is a science-led global healthcare company with a particular purpose: to help people do more, feel better, and live longer. Our approach to Pharmaceutical Research and Development (R&D) focuses on science related to the immune system, the use of human genetics, and advanced technologies and is driven by the multiplier effect of Science x Technology x Culture. 2020 Annual Report; For further information, please visit GSK.
The WHO recommended, on October 6, 2021, 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.
A recent study of variation at the C-terminal sequence, part of RTS,S, demonstrated a slightly diminished efficacy for P. falciparum strains that contain sequences heterologous to RTS,S,8 and suggests that vaccine efficacy may depend somewhat on how closely CSP in the community matches that found in the vaccine.
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.
About 2,000 cases of malaria are diagnosed in the United States annually, mostly in returned travelers, says the U.S. CDC. Travelers to sub-Saharan Africa have the most significant risk of both getting malaria and dying from their infection.
Mosquirix is administered as an intramuscular injection. Phase 3 studies evaluated three and four doses. The WHO says the RTS,S/AS01 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.
Mosquirix Side Effects
With regard to vaccine safety, the RTS,S/AS01 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.
World Malaria (Vaccine) Day 2022
World Malaria Day 2022 is celebrated on April 25, 2022. According to the 2021 World malaria report, global progress in reducing malaria cases and deaths has slowed or stalled in recent years, particularly in countries hardest hit by the disease. The report notes the need for continued innovation in the research and development of new tools if the world achieves the 2030 targets of the WHO malaria strategy.
Mosquirix News: 2015 - 2022
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... and WHO's prequalification paves the way for more children to benefit from the vaccine."
August 16, 2022 - UNICEF awarded a contract to GSK with a value of up to USD 170 million that will lead to 18 million doses of RTS,S/AS01 (RTS,S) being available over the next three years.
June 17, 2022 - Scientists from the German Cancer Research Center announced a new study found: 'explain why natural infections, to which people in endemic areas are constantly exposed, offer little protection against new diseases with other strains, and why the effect of the vaccination available to date lasts only a short time.'
May 16, 2022 - Detailed analysis of mosquito bites in the Central African Republic found that, contrary to assumptions, many occur indoors during the daytime when people are not well protected by traditional anti-malaria defenses
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.
February 22, 2022 - BMC published: Impact of seasonal RTS,S/AS01E vaccination plus seasonal malaria chemoprevention on the nutritional status of children in Burkina Faso and Mali. Despite a high burden of malnutrition and malaria in the study populations and a major reduction in the incidence of malaria in children receiving both interventions, this had only a modest impact on nutritional status. Therefore, other interventions are needed to reduce the high burden of malnutrition in these areas.
December 22, 2021 - The Lancet Infectious Diseases published a Personal View: Spend wisely to eliminate malaria.
December 15, 2021 - Dr. Pedro Alonso, Director, WHO Global Malaria Programme, issued a Letter that stated: Demand for the RTS,S vaccine is expected to be high, and supply in the near to medium term be limited. Current vaccine production capacity stands at 15 million doses per year, while demand is estimated at more than 80 million doses annually.
December 6, 2021 - New data from the World Health Organization reveal that the COVID-19 pandemic has disrupted malaria services, leading to a marked increase in cases and deaths. According to WHO's latest World malaria report, there were an estimated 241 million malaria cases and 627,000 malaria deaths worldwide in 2020. And the WHO welcomed the Gavi Alliance Board's investment in the first malaria vaccine program.
December 2, 2021 - The Board of Gavi, the Vaccine Alliance, approved an investment to support the malaria vaccine introduction, procurement, and delivery for Gavi-eligible countries in sub-Saharan Africa in 2022-2025. An initial investment of US$ 155.7 million for 2022-2025 will initiate the implementation of the RTS,S malaria vaccine.
November 5, 2021 - The Hill reported 'There are multiple strains of malaria, and the parasite is capable of evolving and growing resistant to treatments, so individuals can contract malaria more than once in a lifetime. This has complicated the development of a vaccine.'
November 5, 2021 - Djermakoye Hadiza Jackou, coordinator of Niger's National Malaria Control Programme (PNLP), said the WHO announcement was "welcomed with great joy".
November 1, 2021 - Science Direct published: How can we develop an effective subunit vaccine to achieve successful malaria eradication?
October 27, 2021 - GSK confirmed the World Health Organization recommended a broader roll-out of the RTS,S/AS01e malaria vaccine to reduce childhood illness and deaths from malaria in children living in sub-Saharan Africa and other regions with moderate to high malaria transmission.
October 16, 2021 - The WHO Africa published an article: Breakthrough Malaria Vaccine – Ndhiwa Community Speaks Out.
October 14, 2021 - The Indian Express published an audio: An expert on why the malaria vaccine matters, and the reason it took so long.
October 14, 2021 - The Hill published: Malaria vaccine is a triumph for global public health.
October 8, 2021 - The journal Nature published: Scientists hail historic malaria vaccine approval — but point to challenges ahead. The WHO-approved RTS,S vaccine has modest efficacy and requires a complex regimen of doses, so ample funding and clear communication will be crucial to success.
October 8, 2021 - "This is the most exciting malaria news in years," said 2019 President Chandy John, MD, Director of the Ryan White Center for Pediatric Infectious Diseases and Global Health at Indiana University School of Medicine. "This vaccine could be a game-changer when it comes to saving tens of thousands of young lives that are cut short each year by malaria. To have a vaccine available for children that will decrease the risk of severe malaria by 30% is a major step forward in the work of malaria elimination and eradication.
October 7, 2021 - The National Geographic published: 'Historic moment': Why the WHO endorsed the first malaria vaccine.
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.
October 6, 2021 - PATH applauds the World Health Organization recommending for broader use of the world's first malaria vaccine, RTS,S/AS01E (RTS,S). This historic recommendation means that the vaccine, which is currently in routine use as part of a pilot program in areas of Ghana, Kenya, and Malawi, can soon be available in other malaria-endemic nations as well.
October 5, 2021 - The journal Nature published a study: Afucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination, that concluded by saying 'show that naturally acquired PfEMP1-specific IgG is strongly afucosylated in a stable and exposure-dependent manner, and efficiently induces FcγRIIIa-dependent natural killer (NK) cell degranulation. In contrast, immunization with a subunit PfEMP1 (VAR2CSA) vaccine results in fully fucosylated specific IgG. These results have implications for understanding protective natural- and vaccine-induced immunity to malaria.'
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.
August 25, 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.
August 4, 2021 - In advance of key decisions from WHO and Gavi and to address the associated uncertainty around future demand, Gavi, GSK, and MedAccess have developed an innovative financing solution to ensure continuous manufacturing of the vaccine antigen RTS,S so that it will be immediately available should there be a positive decision to move forward.
June 30, 2021 - The WHO announced China had been awarded a malaria-free certification. "Today, we congratulate the people of China on ridding the country of malaria," said Dr. Tedros Adhanom Ghebreyesus, WHO Director-General. "Their success was hard-earned and came only after decades of targeted and sustained action. With this announcement, China joins the growing number of countries that are showing the world that a malaria-free future is a viable goal."
April 21, 2021 - The WHO announced a new initiative to halt disease transmission in 25 more countries by 2025. Of the 87 countries with malaria, 46 reported fewer than 10 000 cases of the disease in 2019 compared to 26 countries in 2000. By the end of 2020, 24 countries had reported interrupting malaria transmission for 3 years or more. Of these, 11 were certified malaria-free by WHO.
March 17, 2021 - Study: Adverse pregnancy outcomes among women presenting at antenatal clinics in Ouélessébougou, Mali. Conclusion: Low gravidity and young age predict perinatal death and PTD. The information collected here can be used as a baseline for adverse pregnancy outcomes in future vaccine trials in pregnant women.
March 12, 2021 - Review: Towards Eradication of Malaria: Is the WHO's RTS,S/AS01 Vaccination Effective Enough?
March 1, 2021 - The U.S. CDC reported a malaria epidemic is ongoing in Burundi. Since January 1, 2019, the Ministry of Health has reported nearly 6 million cases (out of a total population of approximately 12 million), with more than 1,800 deaths.
February 25, 2021 - The WHO reported El Salvador today became the first country in Central America to be awarded a certification of malaria elimination by the World Health Organization. The certification follows more than 50 years of commitment by the Salvadoran government and people to ending the disease in a country with a dense population and geography hospitable to malaria.
January 27, 2021 - GSK, PATH, and Bharat Biotech (BBIL) announced a product transfer agreement for the malaria vaccine, RTS,S/AS01E. The agreement includes the transfer of manufacturing of the RTS,S antigen part of the vaccine, and a license on all rights of the RTS,S/AS01 malaria vaccine to BBIL. In addition, GSK will retain the adjuvant's production (AS01E) and supply it to BBIL.
January 27, 2021 - Fighting malaria in the lab and on the ground. Malaria is one of the world's oldest diseases, with evidence of the mosquito-borne illness found in tissues from Ancient Egyptian mummies. But despite its long history and our understanding of its biology, malaria remains one of the world's deadliest diseases.
September 8, 2020 - The Nature journal published: The quest for a vaccine against malaria.
August 16, 2019 - Overcoming obstacles to end malaria. The only treatment available for this type of malaria, primaquine, needs to be taken for fourteen days, so it is often associated with poor compliance. To address this and make it easier for patients, we have been developing tafenoquine, in partnership with the not-for-profit foundation Medicines for Malaria Venture (MMV), as a single-dose treatment.
July 19, 2019 - The Lancet published an article: RTS,S malaria vaccine could provide major public health benefits.
July 15, 2021 - Product Review: RTS,S/AS01 vaccine (Mosquirix™): an overview.
August 23, 2017 - Original Research was published. RTS,S/AS01E Malaria Vaccine Induces Memory and Polyfunctional T Cell Responses in a Pediatric African Phase III Trial. 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: final results of phase three, individually randomized, controlled trial.' Interpretation - RTS,S/AS01 prevented a substantial number of cases of clinical malaria over a 3–4 year period in young infants and children when administered with or without a booster dose. Efficacy was enhanced by the administration of a booster dose in both age categories. Thus, the vaccine has the potential to make a substantial contribution to malaria control when used in combination with other effective control measures, especially in areas of high transmission. 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.