Controlled Human Malaria Infections by Intradermal Injection of Cryopreserved Plasmodium Falciparum Sporozoites

Overview

Journal Am J Trop Med Hyg

Specialty Tropical Medicine

Date 2012 Nov 15

PMID 23149582

Citations 95

Authors

Meta Roestenberg

Else M Bijker

B Kim Lee Sim

Peter F Billingsley

Eric R James

Guido J H Bastiaens

Anne C Teirlinck

Anja Scholzen

Karina Teelen

Theo Arens

Andre J A M van der Ven

Anusha Gunasekera

Sumana Chakravarty

Soundarapandian Velmurugan

Cornelus C Hermsen

Robert W Sauerwein

Stephen L Hoffman

Affiliations

Soon will be listed here.

Abstract

Controlled human malaria infection with sporozoites is a standardized and powerful tool for evaluation of malaria vaccine and drug efficacy but so far only applied by exposure to bites of Plasmodium falciparum (Pf)-infected mosquitoes. We assessed in an open label Phase 1 trial, infection after intradermal injection of respectively 2,500, 10,000, or 25,000 aseptic, purified, vialed, cryopreserved Pf sporozoites (PfSPZ) in three groups (N = 6/group) of healthy Dutch volunteers. Infection was safe and parasitemia developed in 15 of 18 volunteers (84%), 5 of 6 volunteers in each group. There were no differences between groups in time until parasitemia by microscopy or quantitative polymerase chain reaction, parasite kinetics, clinical symptoms, or laboratory values. This is the first successful infection by needle and syringe with PfSPZ manufactured in compliance with regulatory standards. After further optimization, the use of such PfSPZ may facilitate and accelerate clinical development of novel malaria drugs and vaccines.

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References

Sauerwein R, Roestenberg M, Moorthy V . Experimental human challenge infections can accelerate clinical malaria vaccine development. Nat Rev Immunol. 2010; 11(1):57-64. DOI: 10.1038/nri2902. View

Hermsen C, Telgt D, Linders E, van de Locht L, Eling W, Mensink E . Detection of Plasmodium falciparum malaria parasites in vivo by real-time quantitative PCR. Mol Biochem Parasitol. 2001; 118(2):247-51. DOI: 10.1016/s0166-6851(01)00379-6. View

Ifediba T, Vanderberg J . Complete in vitro maturation of Plasmodium falciparum gametocytes. Nature. 1981; 294(5839):364-6. DOI: 10.1038/294364a0. View

Nieman A, de Mast Q, Roestenberg M, Wiersma J, Pop G, Stalenhoef A . Cardiac complication after experimental human malaria infection: a case report. Malar J. 2009; 8:277. PMC: 2794284. DOI: 10.1186/1475-2875-8-277. View

Sattabongkot J, Yimamnuaychoke N, Leelaudomlipi S, Rasameesoraj M, Jenwithisuk R, Coleman R . Establishment of a human hepatocyte line that supports in vitro development of the exo-erythrocytic stages of the malaria parasites Plasmodium falciparum and P. vivax. Am J Trop Med Hyg. 2006; 74(5):708-15. View

Holder A . The carboxy-terminus of merozoite surface protein 1: structure, specific antibodies and immunity to malaria. Parasitology. 2009; 136(12):1445-56. DOI: 10.1017/S0031182009990515. View

Hoffman S, Billingsley P, James E, Richman A, Loyevsky M, Li T . Development of a metabolically active, non-replicating sporozoite vaccine to prevent Plasmodium falciparum malaria. Hum Vaccin. 2009; 6(1):97-106. DOI: 10.4161/hv.6.1.10396. View

de Mast Q, Groot E, Lenting P, de Groot P, McCall M, Sauerwein R . Thrombocytopenia and release of activated von Willebrand Factor during early Plasmodium falciparum malaria. J Infect Dis. 2007; 196(4):622-8. DOI: 10.1086/519844. View

McCall M, Netea M, Hermsen C, Jansen T, Jacobs L, Golenbock D . Plasmodium falciparum infection causes proinflammatory priming of human TLR responses. J Immunol. 2007; 179(1):162-71. DOI: 10.4049/jimmunol.179.1.162. View

10.

Rickman L, Jones T, Long G, Paparello S, Schneider I, Paul C . Plasmodium falciparum-infected Anopheles stephensi inconsistently transmit malaria to humans. Am J Trop Med Hyg. 1990; 43(5):441-5. DOI: 10.4269/ajtmh.1990.43.441. View

11.

Najera J, Gonzalez-Silva M, Alonso P . Some lessons for the future from the Global Malaria Eradication Programme (1955-1969). PLoS Med. 2011; 8(1):e1000412. PMC: 3026700. DOI: 10.1371/journal.pmed.1000412. View

12.

Thompson F, Porter D, Okitsu S, Westerfeld N, Vogel D, Todryk S . Evidence of blood stage efficacy with a virosomal malaria vaccine in a phase IIa clinical trial. PLoS One. 2008; 3(1):e1493. PMC: 2204057. DOI: 10.1371/journal.pone.0001493. View

13.

Roestenberg M, OHara G, Duncan C, Epstein J, Edwards N, Scholzen A . Comparison of clinical and parasitological data from controlled human malaria infection trials. PLoS One. 2012; 7(6):e38434. PMC: 3372522. DOI: 10.1371/journal.pone.0038434. View

14.

Hoffman S, Edelman R, Bryan J, Schneider I, Davis J, Sedegah M . Safety, immunogenicity, and efficacy of a malaria sporozoite vaccine administered with monophosphoryl lipid A, cell wall skeleton of mycobacteria, and squalane as adjuvant. Am J Trop Med Hyg. 1994; 51(5):603-12. DOI: 10.4269/ajtmh.1994.51.603. View

15.

Ballou W, Hoffman S, Sherwood J, Hollingdale M, NEVA F, Hockmeyer W . Safety and efficacy of a recombinant DNA Plasmodium falciparum sporozoite vaccine. Lancet. 1987; 1(8545):1277-81. DOI: 10.1016/s0140-6736(87)90540-x. View

16.

Hermsen C, de Vlas S, van Gemert G, Telgt D, Verhage D, Sauerwein R . Testing vaccines in human experimental malaria: statistical analysis of parasitemia measured by a quantitative real-time polymerase chain reaction. Am J Trop Med Hyg. 2004; 71(2):196-201. View

17.

Church L, Le T, Bryan J, Gordon D, Edelman R, Fries L . Clinical manifestations of Plasmodium falciparum malaria experimentally induced by mosquito challenge. J Infect Dis. 1997; 175(4):915-20. DOI: 10.1086/513990. View

18.

Ponnudurai T, Lensen A, van Gemert G, Bensink M, Bolmer M, Meuwissen J . Infectivity of cultured Plasmodium falciparum gametocytes to mosquitoes. Parasitology. 1989; 98 Pt 2:165-73. DOI: 10.1017/s0031182000062065. View

19.

Roestenberg M, McCall M, Hopman J, Wiersma J, Luty A, van Gemert G . Protection against a malaria challenge by sporozoite inoculation. N Engl J Med. 2009; 361(5):468-77. DOI: 10.1056/NEJMoa0805832. View

20.

Chulay J, Schneider I, Cosgriff T, Hoffman S, Ballou W, Quakyi I . Malaria transmitted to humans by mosquitoes infected from cultured Plasmodium falciparum. Am J Trop Med Hyg. 1986; 35(1):66-8. DOI: 10.4269/ajtmh.1986.35.66. View