RTS,S

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RTS,S or Mosquirix is an experimental recombinant protein-based vaccine for malaria.[1]

History[edit]

A completely effective vaccine is not yet available for malaria, although several vaccines are under development. SPf66 was tested extensively in endemic areas in the 1990s, but clinical trials showed it to be insufficiently effective.[2] Other vaccine candidates, targeting the blood-stage of the malaria parasite's life cycle, have also been insufficient on their own.[3] RTS,S is one of several potential vaccines under development that target the pre-erythrocytic stage of the disease. Among them, RTS,S has shown the most promising results so far.[4]

Mechanism[edit]

The RTS,S vaccine was engineered using genes from the repeat and T-cell epitope in the circumsporozoite protein (CSP) of Plasmodium falciparum malaria parasite and a viral envelope protein of the hepatitis B virus (HBsAg) and a chemical adjuvant to boost the immune system response.[5] Infection is prevented by inducing high antibody titers that block the parasite from infecting the liver.[6]

Clinical trials[edit]

The RTS,S-based vaccine formulation had previously been demonstrated to be safe, well tolerated, immunogenic, and to potentially confer partial efficacy in both malaria-naive and -experienced adults as well as children, further research was considered necessary to improve the effectiveness of the vaccine.[7]

In November 2012, findings from a Phase III trial of RTS,S reported that it provided modest protection against both clinical and severe malaria in young infants. In October 2013, GlaxoSmithKline (GSK) reported that the RTS,S vaccine reduced the amount of cases amongst young children by almost 50 percent and among infants by around 25 percent, following the conclusion of an 18-month clinical trial. GlaxoSmithKline submitted an application for a marketing license with the European Medicines Agency (EMA) in July, 2014.[8] The new vaccine has the backing of the UN’s Swiss-based WHO which states that it will recommend the use of RTS,S for use starting in 2015, providing it gets approval.[9]

Funding[edit]

RTS,S is being developed by the non-profit PATH Malaria Vaccine Initiative (MVI), GlaxoSmithKline with funding from the Bill and Melinda Gates Foundation.[10]

References[edit]

  1. ^ Kelland, Kate (Oct 18, 2011). "Malaria scientist celebrates success after 24 years". Reuters. 
  2. ^ Graves, Patricia M; Gelband, Hellen (2006). "Vaccines for preventing malaria (SPf66)". In Graves, Patricia M. Cochrane Database of Systematic Reviews (2): CD005966. doi:10.1002/14651858.CD005966. PMID 16625647. 
  3. ^ Graves, Patricia M; Gelband, Hellen (2006). "Vaccines for preventing malaria (blood-stage)". In Graves, Patricia M. Cochrane Database of Systematic Reviews (4): CD006199. doi:10.1002/14651858.CD006199. PMID 17054281. 
  4. ^ Graves, Patricia M; Gelband, Hellen (2006). "Vaccines for preventing malaria (pre-erythrocytic)". In Graves, Patricia M. Cochrane Database of Systematic Reviews (4): CD006198. doi:10.1002/14651858.CD006198. PMID 17054280. 
  5. ^ Rts, s Clinical Trials; Agnandji, ST; Lell, B; Fernandes, JF; Abossolo, BP; Methogo, BG; Kabwende, AL; Adegnika, AA; Mordmüller, B; Issifou, S; Kremsner, PG; Sacarlal, J; Aide, P; Lanaspa, M; Aponte, JJ; Machevo, S; Acacio, S; Bulo, H; Sigauque, B; MacEte, E; Alonso, P; Abdulla, S; Salim, N; Minja, R; Mpina, M; Ahmed, S; Ali, AM; Mtoro, AT; Hamad, AS; Mutani, P (2012). "A Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Infants". New England Journal of Medicine 367 (24): 2284–95. doi:10.1056/NEJMoa1208394. PMID 23136909. 
  6. ^ Foquet, Lander; Hermsen, Cornelus; van Gemert, Geert-Jan; Van Braeckel, Eva; Weening, Karin; Sauerwein, Robert; Meuleman, Philip; Leroux-Roels, Geert (2014). "Vaccine-induced monoclonal antibodies targeting circumsporozoite protein prevent Plasmodium falciparum infection". Journal of Clinical Investigation 124 (1): 140–4. doi:10.1172/JCI70349. PMC 3871238. PMID 24292709. 
  7. ^ Regules, Jason A; Cummings, James F; Ockenhouse, Christian F (2011). "The RTS,S vaccine candidate for malaria". Expert Review of Vaccines 10 (5): 589–99. doi:10.1586/erv.11.57. PMID 21604980. 
  8. ^ Plumridge, Hester (24 July 2014). "Glaxo Files Its Entry in Race for a Malaria Vaccine". The Wall Street Journal. Retrieved 30 July 2014. 
  9. ^ Kelland, Kate (7 October 2013). "GSK aims to market world’s first malaria vaccine". Reuters. Retrieved 9 December 2013. 
  10. ^ Stein, Rob (October 18, 2011). "Experimental malaria vaccine protects many children, study shows". Washington Post. 

Bibliography[edit]

  • Wilby, K. J.; Lau, T. T.; Gilchrist, S. E.; Ensom, M. H. (2012). "Mosquirix (RTS,S): A Novel Vaccine for the Prevention of Plasmodium falciparum Malaria". Annals of Pharmacotherapy 46 (3): 384–93. doi:10.1345/aph.1Q634. PMID 22408046. 
  • Agnandji, ST; Lell, B; Soulanoudjingar, SS; Fernandes, JF; Abossolo, BP; Conzelmann, C; Methogo, BG; Doucka, Y; Flamen, A; Mordmüller, B; Issifou, S; Kremsner, PG; Sacarlal, J; Aide, P; Lanaspa, M; Aponte, JJ; Nhamuave, A; Quelhas, D; Bassat, Q; Mandjate, S; MacEte, E; Alonso, P; Abdulla, S; Salim, N; Juma, O; Shomari, M; Shubis, K; Machera, F; Hamad, AS; Minja, R (2011). "First Results of Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Children". New England Journal of Medicine 365 (20): 1863–75. doi:10.1056/NEJMoa1102287. PMID 22007715. 
  • Asante, Kwaku Poku; Abdulla, Salim; Agnandji, Selidji; Lyimo, John; Vekemans, Johan; Soulanoudjingar, Solange; Owusu, Ruth; Shomari, Mwanajaa; Leach, Amanda; Jongert, Erik; Salim, Nahya; Fernandes, Jose F; Dosoo, David; Chikawe, Maria; Issifou, Saadou; Osei-Kwakye, Kingsley; Lievens, Marc; Paricek, Maria; Möller, Tina; Apanga, Stephen; Mwangoka, Grace; Dubois, Marie-Claude; Madi, Tigani; Kwara, Evans; Minja, Rose; Hounkpatin, Aurore B; Boahen, Owusu; Kayan, Kingsley; Adjei, George; Chandramohan, Daniel (2011). "Safety and efficacy of the RTS,S/AS01E candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 19 month follow-up of a randomised, open-label, phase 2 trial". The Lancet Infectious Diseases 11 (10): 741–9. doi:10.1016/S1473-3099(11)70100-1. PMID 21782519. 

See also[edit]