NF135.C10: a new Plasmodium falciparum clone for controlled human malaria infections

Anne C Teirlinck, Meta Roestenberg, Marga van de Vegte-Bolmer, Anja Scholzen, Moniek J L Heinrichs, Rianne Siebelink-Stoter, Wouter Graumans, Geert-Jan van Gemert, Karina Teelen, Martijn W Vos, Krystelle Nganou-Makamdop, Steffen Borrmann, Yolanda P A Rozier, Marianne A A Erkens, Adrian J F Luty, Cornelus C Hermsen, B Kim Lee Sim, Lisette van Lieshout, Stephen L Hoffman, Leo G Visser, Robert W Sauerwein, Anne C Teirlinck, Meta Roestenberg, Marga van de Vegte-Bolmer, Anja Scholzen, Moniek J L Heinrichs, Rianne Siebelink-Stoter, Wouter Graumans, Geert-Jan van Gemert, Karina Teelen, Martijn W Vos, Krystelle Nganou-Makamdop, Steffen Borrmann, Yolanda P A Rozier, Marianne A A Erkens, Adrian J F Luty, Cornelus C Hermsen, B Kim Lee Sim, Lisette van Lieshout, Stephen L Hoffman, Leo G Visser, Robert W Sauerwein

Abstract

We established a new field clone of Plasmodium falciparum for use in controlled human malaria infections and vaccine studies to complement the current small portfolio of P. falciparum strains, primarily based on NF54. The Cambodian clone NF135.C10 consistently produced gametocytes and generated substantial numbers of sporozoites in Anopheles mosquitoes and diverged from NF54 parasites by genetic markers. In a controlled human malaria infection trial, 3 of 5 volunteers challenged by mosquitoes infected with NF135.C10 and 4 of 5 challenged with NF54 developed parasitemia as detected with microscopy. The 2 strains induced similar clinical signs and symptoms as well as cellular immunological responses.

Clinical trials registration: NCT01002833.

Figures

Figure 1.
Figure 1.
Parasite kinetics of Plasmodium falciparum strains NF135.C10, and NF54 assessed by quantitative real-time polymerase chain reaction. Volunteers were infected by bites of mosquitoes infected with either NF135.C10 or NF54. A, Parasitemia of volunteers until thick smear positivity; data are shown as geometric means and 95% confidence intervals for volunteers successfully infected with NF135.C10 (red) or NF54 (black) and historical controls infected with NF54 (gray area; n = 48). B, Parasitemia of volunteers at the time of smear positivity and subsequent start of treatment (T), followed up for 3 days and finally at 28 days after infection; data are shown as geometric means and 95% confidence intervals for volunteers successfully infected with NF135.C10 (red; n = 3) or NF54 (black; n = 4).

References

    1. World Health Organization. World malaria report: 2011. Geneva, Switzerland: World Health Organization; 2011.
    1. Sauerwein RW, Roestenberg M, Moorthy VS. Experimental human challenge infections can accelerate clinical malaria vaccine development. Nat Rev. 2011;11:57–64.
    1. Hoffman SL, Goh LM, Luke TC, et al. Protection of humans against malaria by immunization with radiation-attenuated Plasmodium falciparum sporozoites. J Infect Dis. 2002;185:1155–64.
    1. Jeffery GM, Young MD, Burgess RW, Eyles DE. Early activity in sporozoite-induced Plasmodium falciparum infections. Ann Trop Med Parasitol. 1959;53:51–8.
    1. Rieckmann KH, Carson PE, Beaudoin RL, Cassells JS, Sell KW. Letter: Sporozoite induced immunity in man against an Ethiopian strain of Plasmodium falciparum. Trans R Soc Trop Med Hyg. 1974;68:258–9.
    1. Drakeley CJ, Duraisingh MT, Povoa M, Conway DJ, Targett GA, Baker DA. Geographical distribution of a variant epitope of Pfs48/45, a Plasmodium falciparum transmission-blocking vaccine candidate. Mol Biochem Parasitol. 1996;81:253–7.
    1. Ponnudurai T, Lensen AH, Van Gemert GJ, Bensink MP, Bolmer M, Meuwissen JH. Infectivity of cultured Plasmodium falciparum gametocytes to mosquitoes. Parasitology. 1989;98(Pt 2):165–73.
    1. Hermsen CC, Telgt DS, Linders EH, et al. Detection of Plasmodium falciparum malaria parasites in vivo by real-time quantitative PCR. Mol Biochem Parasitol. 2001;118:247–51.
    1. Roestenberg M, de Vlas SJ, Nieman AE, Sauerwein RW, Hermsen CC. Efficacy of pre-erythrocytic and blood-stage malaria vaccines can be assessed in small sporozoite challenge trials in human volunteers. J Infect Dis. 2012;206:319–23.
    1. Roestenberg M, O'Hara GA, Duncan CJ, et al. Comparison of clinical and parasitological data from controlled human malaria infection trials. PLoS One. 2012;7:e38434.
    1. Edelman R, Hoffman SL, Davis JR, et al. Long-term persistence of sterile immunity in a volunteer immunized with X-irradiated Plasmodium falciparum sporozoites. J Infect Dis. 1993;168:1066–70.
    1. Kester KE, McKinney DA, Tornieporth N, et al. Efficacy of recombinant circumsporozoite protein vaccine regimens against experimental Plasmodium falciparum malaria. J Infect Dis. 2001;183:640–7.
    1. Rickman LS, Jones TR, Long GW, et al. Plasmodium falciparum-infected Anopheles stephensi inconsistently transmit malaria to humans. Am J Trop Med Hyg. 1990;43:441–5.
    1. Roestenberg M, Bijker EM, Sim BK, et al. Controlled human malaria infections by intradermal injection of cryopreserved Plasmodium falciparum sporozoites. Am J Trop Med Hyg. 2012 [epub ahead of print]
    1. Borrmann S, Matuschewski K. Protective immunity against malaria by ‘natural immunization’: a question of dose, parasite diversity, or both? Curr Opin Immunol. 2011;23:500–8.
    1. Douradinha B, Mota MM, Luty AJ, Sauerwein RW. Cross-species immunity in malaria vaccine development: two, three, or even four for the price of one? Infect Immun. 2008;76:873–8.

Source: PubMed

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