Malaria vaccine

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A malaria vaccine is a vaccine against plasmodia , the causative agent of malaria .

Vaccines in development

RTS, S

The vaccine RTS, S consists of the CSP from P. falciparum , which has been coupled to HBsAg and an adjuvant, which induces neutralizing antibodies . A pilot should take place in the years 2017 to 2022 . The pharmaceutical company GlaxoSmithKline (GSK) developed and tested RTS, S together with the PATH Malaria Vaccine Initiative over a period of around 30 years. The Bill & Melinda Gates Foundation co- funded the research. Depending on the age of the vaccinated children, the efficiency is between 36.3 and 25.9% with three vaccinations plus one booster vaccinationTemplate: future / in 2 years. The protection is greatest in the first 2 years and continuously decreases.

More vaccines

The first vaccination attempts against malaria were carried out in 1948 with inactivated merozoites from Plasmodium falciparum . However, no reliable method of counting plasmodia existed and the side effects of the adjuvant were pronounced. From 1967 röntgenbestrahlte were sporozoites of P. berghei used which had previously been isolated from the salivary glands of infected mosquitoes. One limitation of the method was the recovery of sufficient amounts of sporozoites. In the 1990s, the peptide vaccine SPf66 ( Serum Plasmodium falciparum version 66 ) was investigated, which contained the circumsporozoite protein (CSP) and the protein MSP-1 as antigens .

The vaccine candidate SPf66 was developed by Patarroyo and colleagues at the Universidad Nacional de Colombia , Bogota, Colombia. SPf66 consists of three peptide epitopes from P. falciparum from various malaria proteins. The peptides are linked by the linker sequence Pro-Asn-Ala-Asn-Pro (PNANP) from the CSP protein of P. falciparum . The monomer has a cysteine ​​group at the C and N terminus, which should allow polymerization and thus a higher molar mass and better immunogenicity. It showed an unsatisfactory effect in clinical trials.

From 2003 the vaccine PfSPZ was investigated, consisting of irradiated sporozoites from P. falciparum , which mediates vaccination protection through cytotoxic T cells .

Supported by the Bill & Melinda Gates Foundation , CureVac wants to research an mRNA -based vaccine that also targets Plasmodium falciparum .

immunology

In the course of vaccine development, experimental approaches investigate the circumsporozoite protein CSP , MSP-1 , PfEMP1 , RIFIN , STEVOR , SURFIN , EBA , PfRh2 and PfRh4 as antigens . Antigens of the liver stage of the plasmodia are e.g. B. LSA-3 , STARP and SALSA . Experimental uses include DNA vaccines and flying syringes .

Individual evidence

  1. ↑ P. Graves, H. Gelband: Vaccines for preventing malaria (pre-erythrocytic). In: The Cochrane database of systematic reviews. Number 4, 2006, S. CD006198, doi : 10.1002 / 14651858.CD006198 , PMID 17054280 .
  2. ↑ L. Foquet, CC Hermsen, GJ van Gemert, E. Van Braeckel, KE Weening, R. Sauerwein, P. Meuleman, G. Leroux-Roels: Vaccine-induced monoclonal antibodies targeting circumsporozoite protein prevent Plasmodium falciparum infection. In: The Journal of clinical investigation. Volume 124, number 1, January 2014, pp. 140-144, doi : 10.1172 / JCI70349 , PMID 24292709 , PMC 3871238 (free full text).
  3. ↑ WHO welcomes support from Gavi for malaria vaccine pilot program. WHO, June 23, 2016, accessed October 29, 2016 (English, Information note).
  4. ↑ Spiegel.de: EU Medicines Agency: First malaria vaccine shortly before approval , accessed on July 24, 2015.
  5. ↑ Tinto H. et al. 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 randomized, controlled trial In: Lancet. N2015 Jul 4; 386 (9988), doi : 10.1016 / S0140-6736 (15) 60721-8 , PMID 25913272 .
  6. ^ J. Freund, KJ Thomson: Immunization of monkeys against malaria by means of killed parasites with adjuvants. In: The American journal of tropical medicine and hygiene. Volume 28, Number 1, January 1948, pp. 1-22, PMID 18898694 .
  7. ↑ RS Nussenzweig, J. Vanderberg, H. Most, C. Orton: Protective immunity produced by the injection of x-irradiated sporozoites of plasmodium berghei. In: Nature. Volume 216, Number 5111, October 1967, pp. 160-162, PMID 6057225 .
  8. ^ KH Rieckmann, PE Carson, RL Beaudoin, JS Cassells, KW Sell: Letter: Sporozoite induced immunity in man against an Ethiopian strain of Plasmodium falciparum. In: Transactions of the Royal Society of Tropical Medicine and Hygiene. Volume 68, Number 3, 1974, pp. 258-259, PMID 4608063 .
  9. ↑ P. Graves, H. Gelband: Vaccines for preventing malaria (SPf66). In: The Cochrane database of systematic reviews. Number 2, 2006, S. CD005966, doi : 10.1002 / 14651858.CD005966 , PMID 16625647 .
  10. ↑ Patarroyo ME., Romero P, et al .: Induction of protective immunity against experimental infection with malaria using synthetic peptides. Nature. 1987 Aug 13-19; 328 (6131): 629-32. PMID 3302727
  11. ↑ Kashala, Oscar, et al. Safety, tolerability and immunogenicity of new formulations of the Plasmodium falciparum malaria peptide vaccine SPf66 combined with the immunological adjuvant QS-21. Vaccine 20.17 (2002): 2263-2277.
  12. ↑ Graves P, Gelband H: Vaccines for preventing malaria (SPf66) . In: Cochrane Database Syst Rev . No. 2, 2006, p. CD005966. doi : 10.1002 / 14651858.CD005966 . PMID 16625647 .
  13. ^ TC Luke, SL Hoffman: Rationale and plans for developing a non-replicating, metabolically active, radiation-attenuated Plasmodium falciparum sporozoite vaccine. In: The Journal of experimental biology. Volume 206, Pt 21 November 2003, pp. 3803-3808, PMID 14506215 .
  14. ↑ JE Epstein, K. Tewari, KE Lyke, BK Sim, PF Billingsley, MB Laurens, A. Gunasekera, S. Chakravarty, ER James, M. Sedegah, A. Richman, S. Velmurugan, S. Reyes, M. Li , K. Tucker, A. Ahumada, AJ Ruben, T. Li, R. Stafford, AG Eappen, C. Tamminga, JW Bennett, CF Ockenhouse, JR Murphy, J. Komisar, N. Thomas, M. Loyevsky, A. Birkett, CV Plowe, C. Loucq, R. Edelman, TL Richie, RA Seder, SL Hoffman: Live attenuated malaria vaccine designed to protect through hepatic CD8⁺ T cell immunity. In: Science. Volume 334, Number 6055, October 2011, pp. 475-480, doi : 10.1126 / science.1211548 , PMID 21903775 .
  15. ↑ Amber Tong: CureVac to develop mRNA-based flu, malaria vaccines with new Gates Foundation grants. In: Endpoint News. February 15, 2018, accessed March 14, 2018 .
  16. ↑ JA Chan, FJ Fowkes, JG Beeson: Surface antigens of Plasmodium falciparum-infected erythrocytes as immune targets and malaria vaccine candidates. In: Cellular and molecular life sciences: CMLS. Volume 71, number 19, October 2014, pp. 3633–3657, doi : 10.1007 / s00018-014-1614-3 , PMID 24691798 , PMC 4160571 (free full text).
  17. ^ A b V. Lorenz, G. Karanis, P. Karanis: Malaria vaccine development and how external forces shape it: an overview. In: International journal of environmental research and public health. Volume 11, number 7, July 2014, pp. 6791-6807, doi : 10.3390 / ijerph110706791 , PMID 24983392 , PMC 4113845 (free full text).
  18. ↑ WN Chia, YS Goh, L. Rénia: Novel approaches to identify protective malaria vaccine candidates. In: Frontiers in microbiology. Volume 5, 2014, p. 586, doi : 10.3389 / fmicb.2014.00586 , PMID 25452745 , PMC 4233905 (free full text).