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malaria vaccine (Mosquirix; RTS,S)

Indications: - prevention of Plasmodium falciparum malaria for children age 5-17 months Dosage: - 3-4 doses; 4 doses recommended (WHO) [8] - booster 18 months after 3 doses improves vaccine efficacy (36% vs 28%)* during 48 month follow-up * efficacy at least in part assessed by identification of malaria infections [3] * vaccine is only 36% effective; protection fades after several months * vaccine efficacy 4.4% at 7 years [5] * all cases of severe malaria were seen > 2.7 years of follow-up after vaccination [5] Adverse effects: - meningitis is more common in children that receive malaria vaccine [1,3] Mechanism of action: - antibodies to Plasmodium falciparum schizont egress antigen-1 (PfSEA-1), a 244 KD parasite antigen expressed in schizont-infected erythrocytes diminish parasite replication by arresting schizont rupture [2] - sporozoite vaccine does not protect against blood-stage parasites; thus, vaccine may slow acquisition of immunity to blood-stage parasites & a rebound phenomenon may occur with high-level exposure to malaria [5] Comparative biology: - mRNA vaccine offers full protection against malaria in mice [7] Notes: - investigational vaccine [1] - pilot implementation program to begin in Ghana, Kenya, & Malawi in 2018 * approved by European Union, July 2015 [4] * approved by WHO October 2021 [8] * Smith-Kline Galaxo

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References

  1. The RTS,S Clinical Trials Partnership First Results of Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Children N Engl J Med, October 18, 2011 PMID: 22007715 http://www.nejm.org/doi/full/10.1056/NEJMoa1102287 - White NJ A Vaccine for Malaria N Engl J Med, October 18, 2011 PMID: 22007716 http://www.nejm.org/doi/full/10.1056/NEJMe1111777
  2. Raj DK et al. Antibodies to PfSEA-1 block parasite egress from RBCs and protect against malaria infection. Science 2014 May 23; 344:871 PMID: 24855263
  3. RTS,S Clinical Trials Partnership Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. Lancet. April 23, 2015 PMID: 25913272 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2815%2960721-8/abstract
  4. Reuters, July 24, 2015 http://www.msn.com/en-us/news/world/worlds-first-malaria-vaccine-gets-go-ahead-from-eu-regulators/ar-AAdqAQR
  5. Olotu A et al. Seven-year efficacy of RTS,S/AS01 malaria vaccine among young African children. N Engl J Med 2016 Jun 30; 374:2519. PMID: 27355532 http://www.nejm.org/doi/10.1056/NEJMoa1515257 - Clemens J, Moorthy V. Implementation of RTS,S/AS01 malaria vaccine - the need for further evidence. N Engl J Med 2016 Jun 30; 374:2596 PMID: 27355540 http://www.nejm.org/doi/10.1056/NEJMe1606007
  6. World Health Organization (WHO). April 24, 2017 Ghana, Kenya and Malawi to take part in WHO malaria vaccine pilot programme. http://www.afro.who.int/en/media-centre/pressreleases/item/9533-ghana-kenya-and-malawi-to-take-part-in-who-malaria-vaccine-pilot-programme.html
  7. Walter Reed Army Institute of Research mRNA vaccine yields full protection against malaria in mice. MedicalXpress 2021 June 18. https://medicalxpress.com/news/2021-06-mrna-vaccine-yields-full-malaria.html
  8. American Medical Association AMA Morning Rounds. Oct 7, 2021 - Firozi P, Iati M, Cunningham E WHO endorses use of first malaria vaccine. Washington Post. October 6, 2021 https://www.washingtonpost.com/health/2021/10/06/who-malaria-vaccine-recommendation/ - Mandavilli A A 'Historic event': First Malaria Vaccine Approved by W.H.O. New York Times. October 6, 2021 https://www.nytimes.com/2021/10/06/health/malaria-vaccine-who.html - Cheng M UN endorses world's 1st malaria vaccine as 'historic moment'. Associated Press (AP) October 6, 2021 https://apnews.com/article/malaria-vaccine-dcb917ea3fbd090484bfe6750d4ea58c - World Health Organization (WHO). WHO recommends groundbreaking malaria vaccine for children at risk. Historic RTS,S/AS01 recommendation can reinvigorate the fight against malaria. News Release. October 6, 2021. https://www.who.int/news/item/06-10-2021-who-recommends-groundbreaking-malaria-vaccine-for-children-at-risk