1921
Volume 78, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

There is increasing interest in malaria vaccines targeting the asexual blood stage of . Without accepted immunologic correlates of clinical protection, challenge studies are useful for assessing the efficacy of candidate vaccines in healthy volunteers. We report a pilot study of a safe and robust challenge protocol using a blood-stage inoculum. We have applied well-validated trial endpoints and twice daily real-time quantitative polymerase chain reaction monitoring of parasitemia to blood-stage challenge, which enabled direct comparison with sporozoite challenge. We found that greater accuracy in quantification of blood-stage growth rates can be achieved with blood-stage challenge. This finding may provide greater power to detect partial efficacy of many blood-stage candidate vaccines. We discuss the potential utility of blood-stage challenge studies in accelerating malaria vaccine development.

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2008-06-01
2017-11-19
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References

  1. Chulay JD, Schneider I, Cosgriff TM, Hoffman SL, Ballou WR, Quakyi IA, Carter R, Trosper JH, Hockmeyer WT, 1986. Malaria transmitted to humans by mosquitoes infected from cultured Plasmodium falciparum. Am J Trop Med Hyg 35 : 66–68.
  2. Marsh K, Kinyanjui S, 2006. Immune effector mechanisms in malaria. Parasite Immunol 28 : 51–60.
  3. Riley EM, Wahl S, Perkins DJ, Schofield L, 2006. Regulating immunity to malaria. Parasite Immunol 28 : 35–49.
  4. Good MF, Stanisic D, Xu H, Elliott S, Wykes M, 2004. The immunological challenge to developing a vaccine to the blood stages of malaria parasites. Immunol Rev 201 : 254–267.
  5. Bergmann-Leitner ES, Duncan EH, Mullen GE, Burge JR, Khan F, Long CA, Angov E, Lyon JA, 2006. Critical evaluation of different methods for measuring the functional activity of antibodies against malaria blood stage antigens. Am J Trop Med Hyg 75 : 437–442.
  6. Shi YP, Udhayakumar V, Oloo AJ, Nahlen BL, Lal AA, 1999. Differential effect and interaction of monocytes, hyperimmune sera, and immunoglobulin G on the growth of asexual stage Plasmodium falciparum parasites. Am J Trop Med Hyg 60 : 135–141.
  7. Chatterjee S, Perignon JL, Van Marck E, Druilhe P, 2006. How reliable are models for malaria vaccine development? Lessons from irradiated sporozoite immunizations. J Postgrad Med 52 : 321–324.
  8. Andrews L, Andersen RF, Webster D, Dunachie S, Walther RM, Bejon P, Hunt-Cooke A, Bergson G, Sanderson F, Hill AV, Gilbert SC, 2005. Quantitative real-time polymerase chain reaction for malaria diagnosis and its use in malaria vaccine clinical trials. Am J Trop Med Hyg 73 : 191–198.
  9. Bejon P, Andrews L, Andersen RF, Dunachie S, Webster D, Walther M, Gilbert SC, Peto T, Hill AV, 2005. Calculation of liver-to-blood inocula, parasite growth rates, and preerythrocytic vaccine efficacy, from serial quantitative polymerase chain reaction studies of volunteers challenged with malaria sporozoites. J Infect Dis 191 : 619–626.
  10. Cheng Q, Lawrence G, Reed C, Stowers A, Ranford-Cartwright L, Creasey A, Carter R, Saul A, 1997. Measurement of Plasmodium falciparum growth rates in vivo: a test of malaria vaccines. Am J Trop Med Hyg 57 : 495–500.
  11. Whitrow M, 1990. Wagner-Jauregg and fever therapy. Med Hist 34 : 294–310.
  12. Dunachie SJ, Walther M, Epstein JE, Keating S, Berthoud T, Andrews L, Andersen RF, Bejon P, Goonetilleke N, Poulton I, Webster DP, Butcher G, Watkins K, Sinden RE, Levine GL, Richie TL, Schneider J, Kaslow D, Gilbert SC, Carucci DJ, Hill AV, 2006. A DNA prime-modified vaccinia virus ankara boost vaccine encoding thrombospondin-related adhesion protein but not circumsporozoite protein partially protects healthy malaria-naive adults against Plasmodium falciparum sporozoite challenge. Infect Immun 74 : 5933–5942.
  13. Lawrence G, Cheng QQ, Reed C, Taylor D, Stowers A, Cloonan N, Rzepczyk C, Smillie A, Anderson K, Pombo D, Allworth A, Eisen D, Anders R, Saul A, 2000. Effect of vaccination with 3 recombinant asexual-stage malaria antigens on initial growth rates of Plasmodium falciparum in non-immune volunteers. Vaccine 18 : 1925–1931.
  14. Simpson JA, Aarons L, Collins WE, Jeffery GM, White NJ, 2002. Population dynamics of untreated Plasmodium falciparum malaria within the adult human host during the expansion phase of the infection. Parasitology 124 : 247–263.
  15. Walther M, Dunachie S, Keating S, Vuola JM, Berthoud T, Schmidt A, Maier C, Andrews L, Andersen RF, Gilbert S, Poulton I, Webster D, Dubovsky F, Tierney E, Sarpotdar P, Correa S, Huntcooke A, Butcher G, Williams J, Sinden RE, Thornton GB, Hill AV, 2005. Safety, immunogenicity and efficacy of a pre-erythrocytic malaria candidate vaccine, ICC-1132 formulated in Seppic ISA 720. Vaccine 23 : 857–864.
  16. Pombo DJ, Lawrence G, Hirunpetcharat C, Rzepczyk C, Bryden M, Cloonan N, Anderson K, Mahakunkijcharoen Y, Martin LB, Wilson D, Elliott S, Elliott S, Eisen DP, Weinberg JB, Saul A, Good MF, 2002. Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum. Lancet 360 : 610–617.
  17. Whyte GS, Savoia HF, 1997. The risk of transmitting HCV, HBV or HIV by blood transfusion in Victoria. Med J Aust 166 : 584–586.
  18. Hirunpetcharat C, Vukovic P, Liu XQ, Kaslow DC, Miller LH, Good MF, 1999. Absolute requirement for an active immune response involving B cells and Th cells in immunity to Plasmodium yoelii passively acquired with antibodies to the 19-kDa carboxyl-terminal fragment of merozoite surface protein- 1. J Immunol 162 : 7309–7314.
  19. Genton B, Al Yaman F, Betuela I, Anders RF, Saul A, Baea K, Mellombo M, Taraika J, Brown GV, Pye D, Irving DO, Felger I, Beck HP, Smith TA, Alpers MP, 2003. Safety and immunogenicity of a three-component blood-stage malaria vaccine (MSP1, MSP2, RESA) against Plasmodium falciparum in Papua New Guinean children. Vaccine 22 : 30–41.
  20. Bottius E, Guanzirolli A, Trape JF, Rogier C, Konate L, Druilhe P, 1996. Malaria: even more chronic in nature than previously thought; evidence for subpatent parasitaemia detectable by the polymerase chain reaction. Trans R Soc Trop Med Hyg 90 : 15–19.
  21. Druilhe P, Perignon JL, 1997. A hypothesis about the chronicity of malaria infection. Parasitol Today 13 : 353–357.
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  • Received : 03 Dec 2007
  • Accepted : 17 Jan 2008

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