Challenges of Assessing the Clinical Efficacy of Asexual Blood-stage Plasmodium Falciparum Malaria Vaccines

Overview

Journal Hum Vaccin Immunother

Specialty Allergy & Immunology

Date 2013 Jun 20

PMID 23778312

Citations 27

Authors

Susanne H Sheehy

Alexander D Douglas

Simon J Draper

Affiliations

Soon will be listed here.

Abstract

In the absence of any highly effective vaccine candidate against Plasmodium falciparum malaria, it remains imperative for the field to pursue all avenues that may lead to the successful development of such a formulation. The development of a subunit vaccine targeting the asexual blood-stage of Plasmodium falciparum malaria infection has proven particularly challenging with only limited success to date in clinical trials. However, only a fraction of potential blood-stage vaccine antigens have been evaluated as targets, and a number of new promising candidate antigen formulations and delivery platforms are approaching clinical development. It is therefore essential that reliable and sensitive methods of detecting, or ruling out, even modest efficacy of blood-stage vaccines in small clinical trials be established. In this article we evaluate the challenges facing blood-stage vaccine developers, assess the appropriateness and limitations of various in vivo approaches for efficacy assessment and suggest future directions for the field.

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References

Murphy S, Prentice J, Williamson K, Wallis C, Fang F, Fried M . Real-time quantitative reverse transcription PCR for monitoring of blood-stage Plasmodium falciparum infections in malaria human challenge trials. Am J Trop Med Hyg. 2012; 86(3):383-94. PMC: 3284350. DOI: 10.4269/ajtmh.2012.10-0658. View

Engwerda C, Minigo G, Amante F, McCarthy J . Experimentally induced blood stage malaria infection as a tool for clinical research. Trends Parasitol. 2012; 28(11):515-21. DOI: 10.1016/j.pt.2012.09.001. View

Pinzon-Charry A, Good M . Malaria vaccines: the case for a whole-organism approach. Expert Opin Biol Ther. 2008; 8(4):441-8. DOI: 10.1517/14712598.8.4.441. View

Sheehy S, Spencer A, Douglas A, Sim B, Longley R, Edwards N . Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe. PLoS One. 2013; 8(6):e65960. PMC: 3688861. DOI: 10.1371/journal.pone.0065960. View

Cervia J, Wenz B, Ortolano G . Leukocyte reduction's role in the attenuation of infection risks among transfusion recipients. Clin Infect Dis. 2007; 45(8):1008-13. DOI: 10.1086/521896. View

McCarthy J, Good M . Whole parasite blood stage malaria vaccines: a convergence of evidence. Hum Vaccin. 2009; 6(1):114-23. DOI: 10.4161/hv.6.1.10394. View

Singh S, Miura K, Zhou H, Muratova O, Keegan B, Miles A . Immunity to recombinant plasmodium falciparum merozoite surface protein 1 (MSP1): protection in Aotus nancymai monkeys strongly correlates with anti-MSP1 antibody titer and in vitro parasite-inhibitory activity. Infect Immun. 2006; 74(8):4573-80. PMC: 1539572. DOI: 10.1128/IAI.01679-05. View

Ota M, Odutola A, Owiafe P, Donkor S, Owolabi O, Brittain N . Immunogenicity of the tuberculosis vaccine MVA85A is reduced by coadministration with EPI vaccines in a randomized controlled trial in Gambian infants. Sci Transl Med. 2011; 3(88):88ra56. DOI: 10.1126/scitranslmed.3002461. View

Drakeley C, Sutherland C, Bousema J, Sauerwein R, Targett G . The epidemiology of Plasmodium falciparum gametocytes: weapons of mass dispersion. Trends Parasitol. 2006; 22(9):424-30. DOI: 10.1016/j.pt.2006.07.001. View

10.

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

11.

Hisaeda H, Saul A, Reece J, Kennedy M, Long C, Miller L . Merozoite surface protein 3 and protection against malaria in Aotus nancymai monkeys. J Infect Dis. 2002; 185(5):657-64. DOI: 10.1086/339187. View

12.

Roestenberg M, Bijker E, Sim B, Billingsley P, James E, Bastiaens G . Controlled human malaria infections by intradermal injection of cryopreserved Plasmodium falciparum sporozoites. Am J Trop Med Hyg. 2012; 88(1):5-13. PMC: 3541746. DOI: 10.4269/ajtmh.2012.12-0613. View

13.

Bergmann-Leitner E, Duncan E, Burge J, Spring M, Angov E . Miniaturization of a high-throughput pLDH-based Plasmodium falciparum growth inhibition assay for small volume samples from preclinical and clinical vaccine trials. Am J Trop Med Hyg. 2008; 78(3):468-71. View

14.

Agnandji S, Lell B, Fernandes J, Abossolo B, Methogo B, Lumeka Kabwende A . A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. N Engl J Med. 2012; 367(24):2284-95. PMC: 10915853. DOI: 10.1056/NEJMoa1208394. View

15.

Bejon P, Andrews L, Andersen R, Dunachie S, Webster D, Walther M . 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. 2005; 191(4):619-26. DOI: 10.1086/427243. View

16.

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

17.

Duncan C, Draper S . Controlled human blood stage malaria infection: current status and potential applications. Am J Trop Med Hyg. 2012; 86(4):561-5. PMC: 3403771. DOI: 10.4269/ajtmh.2012.11-0504. View

18.

Druilhe P, Spertini F, Soesoe D, Corradin G, Mejia P, Singh S . A malaria vaccine that elicits in humans antibodies able to kill Plasmodium falciparum. PLoS Med. 2005; 2(11):e344. PMC: 1277929. DOI: 10.1371/journal.pmed.0020344. View

19.

Pollard A, Savulescu J, Oxford J, Hill A, Levine M, Lewis D . Human microbial challenge: the ultimate animal model. Lancet Infect Dis. 2012; 12(12):903-5. DOI: 10.1016/S1473-3099(12)70292-X. View

20.

Draper S, Goodman A, Biswas S, Forbes E, Moore A, Gilbert S . Recombinant viral vaccines expressing merozoite surface protein-1 induce antibody- and T cell-mediated multistage protection against malaria. Cell Host Microbe. 2009; 5(1):95-105. PMC: 2663714. DOI: 10.1016/j.chom.2008.12.004. View