Asexual blood-stage malaria vaccine development: Facing the challenges

Current Opinion in Infectious Diseases

Volumn 20, Issue 5, 2007, Pages 467-475

  Genton, Blaise ^a,b   Reed, Zarifah H ^c  

^a IFAKARA HEALTH INSTITUTE   (Tanzania)

^b SWISS TROPICAL AND PUBLIC HEALTH INSTITUTE   (Switzerland)

^c WORLD HEALTH ORGANIZATION   (Switzerland)

Author keywords

Asexual blood stage; Clinical trial; Malaria; Plasmodium falciparum; Review; Vaccine

Indexed keywords

3D7 MSP 2 VACCINE; ALUMINUM HYDROXIDE; APICAL MEMBRANE ANTIGEN 1; AS 02A; AS 02A VACCINE; BINDING PROTEIN; CHIMERIC ANTIBODY; CHIMERIC FUSION PROTEIN; CPG 7909; ERYTHROCYTE BINDING ANTIGEN 175; ERYTHROCYTE MEMBRANE PROTEIN 1; FANSIDAR; FVO 25545; GLUTAMATE RICH PROTEIN; HYBRID PROTEIN; MALARIA VACCINE; MEMBRANE PROTEIN; MEROZOITE SURFACE PROTEIN 1; MEROZOITE SURFACE PROTEIN 2; MEROZOITE SURFACE PROTEIN 3; MEROZOITE SURFACE PROTEIN 4; MEROZOITE SURFACE PROTEIN 5; MICROORGANISM PROTEIN; PARASITE ANTIGEN; PEV 301T; PFCP 29; SERINE REPEAT ANTIGEN; UNCLASSIFIED DRUG;

ANTIGENICITY; CLINICAL TRIAL; DRUG EFFICACY; EFFECTOR CELL; ENDEMIC DISEASE; ENZYME POLYMORPHISM; HUMAN; IMMUNITY; IN VITRO STUDY; IN VIVO STUDY; MALARIA; NONHUMAN; REVIEW;

ANIMALS; ANTIGENS, PROTOZOAN; CLINICAL TRIALS AS TOPIC; HUMANS; MALARIA; MALARIA VACCINES; PLASMODIUM; POLYMORPHISM, GENETIC;

EID: 34548425095     PISSN: 09517375     EISSN: None     Source Type: Journal    
DOI: 10.1097/QCO.0b013e3282dd7a29     Document Type: Review

References (57)

1. Pombo DJ, Lawrence G, Hirunpetcharat C, et al. Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum. Lancet 2002; 360:610-617.
2. Genton B, Betuela I, Felger I, et al. A recombinant blood-stage malaria vaccine reduces Plasmodium falciparum density and exerts selective pressure on parasite populations in a phase 1-2b trial in Papua New Guinea. J Infect Dis 2002; 185:820-827.
3. Graves P, Gelband H. Vaccines for preventing malaria (blood-stage). Cochrane Database Syst Rev 2006; CD006199. This Cochrane review describes the results of trials of asexual blood-stage vaccines. Only one (MSP/RESA, also known as Combination B) has been tested in a randomized controlled trial and this candidate showed promise as a way to reduce the severity of malaria episodes, but the effect of the vaccine was MSP2 variant-specific.
4. Gardner MJ, Hall N, Fung E, et al. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 2002; 419:498-511.
5. Mu J, Awadalla P, Duan J, et al. Genome-wide variation and identification of vaccine targets in the Plasmodium falciparum genome. Nat Genet 2007; 39:126-130. This paper reports on a genome-wide survey for polymorphism and signature of selections that allowed the identification of potential vaccine targets.
6. Kanoi BN, Egwang TG. New concepts in vaccine development in malaria. Curr Opin Infect Dis 2007; 20:311-316. This review summarizes the new concepts in vaccine development in malaria, starting from attenuated sporozoite vaccines, to reverse vaccinology, in-vitro surrogate markers of vaccine efficacy, immunology and novel adjuvants and vaccine delivery systems.
7. Sundaresh S, Doolan DL, Hirst S, et al. Identification of humoral immune responses in protein microarrays using DNA microarray data analysis techniques. Bioinformatics 2006; 22:1760-1766.
8. Davies DH, Liang X, Hernandez JE, et al. Profiling the humoral immune response to infection by using proteome microarrays: high-throughput vaccine and diagnostic antigen discovery. Proc Natl Acad Sci U S A 2005; 102:547-552.
9. Corradin G, Villard V, Kajava AV. Protein structure based strategies for antigen discovery and vaccine development against malaria and other pathogens. Endocr Metab Immune Disord Drug Targets (in press).
10. Villard V, Agak GW, Frank G, et al. Rapid identification of malaria vaccine candidates based on a-helical coiled coil protein motif. PLoS One (in press).
11. Greenwood B. Malaria vaccines. Evaluation and implementation. Acta Trop 2005; 95:298-304.
12. Kidgell C, Volkman SK, Daily J, et al. A systematic map of genetic variation in Plasmodium falciparum. PLoS Pathog 2006; 2:e57. By performing a full-genome scan of allelic variability in 14 field and laboratory strains of P. falciparum, 500 genes evolving at higher than neutral rates were identified. The majority of the most variable genes have paralogs within the P. falciparum genome and may be subject to a different evolutionary clock than those without. The group of 211 variable genes without paralogs contains most known immunogens and a few drug targets, consistent with the idea that the human immune system and drug use is driving parasite evolution.
13. Cortes A, Mellombo M, Mueller I, et al. Geographical structure of diversity and differences between symptomatic and asymptomatic infections for Plasmodium falciparum vaccine candidate AMA1. Infect Immun 2003; 71:1416-1426.
14. Kennedy MC, Wang J, Zhang Y, et al. In vitro studies with recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1): production and activity of an AMA1 vaccine and generation of a multiallelic response. Infect Immun 2002; 70:6948-6960.
15. 19 polymorphisms may be relevant to cross-protective immunity.
16. Sutherland C. A challenge for the development of malaria vaccines: polymorphic target antigens. PLoS Med 2007; 4:e116.
17. Polley SD, Tetteh KK, Lloyd JM, et al. Plasmodium falciparum merozoite surface protein 3 is a target of allele-specific immunity and alleles are maintained by natural selection. J Infect Dis 2007; 195:279-287.
18. Druilhe P, Spertini F, Soesoe D, et al. A malaria vaccine that elicits in humans antibodies able to kill Plasmodium falciparum. PLoS Med 2005; 2:e344.
19. Saul A. Malaria vaccines based on the Plasmodium falciparum merozoite surface protein 3-should we avoid amino acid sequence polymorphisms or embrace them? J Infect Dis 2007; 195:171-173.
20. Diallo TO, Spiegel A, Diouf A, et al. Short report: differential evolution of immunoglobulin G1/G3 antibody responses to Plasmodium falciparum MSP1(19) over time in malaria-immune adult Senegalese patients. Am J Trop Med Hyg 2002; 66:137-139.
21. Bergmann-Leitner ES, Duncan EH, Mullen GE, et al. Critical evaluation of different methods for measuring the functional activity of antibodies against malaria blood stage antigens. Am J Trop Med Hyg 2006; 75:437-442. Asexual blood-stage candidates were evaluated based on their ability to induce antibodies with antiparasite activity. Four methods with regards to their ability to differentiate between invasion or growth inhibitory activities of antibodies specific for two distinct blood-stage antigens, AMA1 and MSP1(42), were evaluated. It was concluded that antibodies induced by these vaccine candidates had different modes of action that varied not only by the antigen, but also by the strain of parasite being tested.
22. Marsh K, Kinyanjui S. Immune effector mechanisms in malaria. Parasite Immunol 2006; 28:51-60. The authors address methodological issues of defining protection and immune responses. They suggest relevant studies that combine functional assays with new approaches such as allelic exchange and gene knockout to better define key targets and mechanisms.
23. Nwuba RI, Sodeinde O, Anumudu CI, et al. The human immune response to Plasmodium falciparum includes both antibodies that inhibit merozoite surface protein 1 secondary processing and blocking antibodies. Infect Immun 2002; 70:5328-5331.
24. Bouharoun-Tayoun H, Attanath P, Sabchareon A, et al. Antibodies that protect humans against Plasmodium falciparum blood stages do not on their own inhibit parasite growth and invasion in vitro, but act in cooperation with monocytes. J Exp Med 1990; 172:1633-1641.
25. Persson KE, Lee CT, Marsh K, Beeson JG. Development and optimization of high-throughput methods to measure Plasmodium falciparum-specific growth inhibitory antibodies. J Clin Microbiol 2006; 44:1665-1673.
26. John CC, O'Donnell RA, Sumba PO, et al. Evidence that invasion-inhibitory antibodies specific for the 19-kDa fragment of merozoite surface protein-1 (MSP-1 19) can play a protective role against blood-stage Plasmodium falciparum infection in individuals in a malaria endemic area of Africa. J Immunol 2004; 173:666-672.
27. Girard MP, Reed ZH, Friede M, Kieny MP. A review of human vaccine research and development: malaria. Vaccine 2007; 25:1567-1580. This is the most comprehensive and updated review of all aspects of malaria vaccine research and development.
28. Wu Y, Przysiecki C, Flanagan E, et al. Sustained high-titer antibody responses induced by conjugating a malarial vaccine candidate to outer-membrane protein complex. Proc Natl Acad Sci U S A 2006; 103:18243-18248.
29. Corradin G. Peptide based malaria vaccine development: personal considerations. Microbes Infect 2007; 9:767-771.
30. Mueller MS, Renard A, Boato F, et al. Induction of parasite growth-inhibitory antibodies by a virosomal formulation of a peptidomimetic of loop I from domain III of Plasmodium falciparum apical membrane antigen 1. Infect Immun 2003; 71:4749-4758.
31. Bentley GA. Functional and immunological insights from the three-dimensional structures of Plasmodium surface proteins. Curr Opin Microbiol 2006; 9:395-400.
32. Westerfeld N, Pluschke G, Zurbriggen R. Optimized Malaria-antigens delivered by immunostimulating reconstituted influenza virosomes. Wien Klin Wochenschr 2006; 118:50-57.
33. Hirunpetcharat C, Wipasa J, Sakkhachornphop S, et al. CpG oligodeoxynucleotide enhances immunity against blood-stage malaria infection in mice parenterally immunized with a yeast-expressed 19 kDa carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein-1 (MSP1(19)) formulated in oil-based Montanides. Vaccine 2003; 21:2923-2932.
34. Jeamwattanalert P, Mahakunkijcharoen Y, Kittigul L, et al. Long-lasting protective immune response to the 19-kilodalton carboxy-terminal fragment of Plasmodium yoelii merozoite surface protein 1 in mice. Clin Vaccine Immunol 2007; 14:342-347.
35. Mullen GE, Giersing BK, Jose-Popoola O, et al. Enhancement of functional antibody responses to AMA1-C1/Alhydrogel, a Plasmodium falciparum malaria vaccine, with CpG oligodeoxynucleotide. Vaccine 2006; 24:2497-2505.
36. Graves P, Gelband H. Vaccines for preventing malaria (SPf66). Cochrane Database Syst Rev 2006; CD005966.
37. Reed ZH, Friede M, Kieny MP. Malaria vaccine development: progress and challenges. Curr Mol Med 2006; 6:231-245.
38. Lawrence G, Cheng QQ, Reed C, et al. Effect of vaccination with 3 recombinant asexual-stage malaria antigens on initial growth rates of Plasmodium falciparum in nonimmune volunteers. Vaccine 2000; 18:1925-1931.
39. Genton B, Al-Yaman F, Betuela I, et al. Safety and immunogenicity of a three-component blood-stage malaria vaccine (MSP1, MSP2, RESA) against Plasmodium falciparum in Papua New Guinean children. Vaccine 2003; 22:30-41.
40. Ockenhouse CF, Angov E, Kester KE, et al. Phase I safety and immunogenicity trial of FMP1/AS02A, a Plasmodium falciparum MSP-1 asexual blood stage vaccine. Vaccine 2006; 24:3009-3017.
41. Stoute JA, Gombe J, Withers MR, et al. Phase 1 randomized double-blind safety and immunogenicity trial of Plasmodium falciparum malaria merozoite surface protein FMP1 vaccine, adjuvanted with AS02A, in adults in western Kenya. Vaccine 2007; 25:176-184.
42. Thera MA, Doumbo OK, Coulibaly D, et al. Safety and allele-specific immunogenicity of a malaria vaccine in malian adults: results of a phase I randomized trial. PLoS Clin Trials 2006; 1:e34.
43. Withers MR, McKinney D, Ogutu BR, et al. Safety and reactogenicity of an MSP-1 malaria vaccine candidate: a randomized phase Ib dose-escalation trial in Kenyan children. PLoS Clin Trials 2006; 1:e32.
44. Malkin E, Long CA, Stowers AW, et al. Phase 1 study of two merozoite surface protein 1 (MSP1(42)) vaccines for Plasmodium falciparum malaria. PLoS Clin Trials 2007; 2:e12.
45. Malkin EM, Diemert DJ, McArthur JH, et al. Phase 1 clinical trial of apical membrane antigen 1: an asexual blood-stage vaccine for Plasmodium falciparum malaria. Infect Immun 2005; 73:3677-3685.
46. Polhemus ME, Magill AJ, Cummings JF, et al. Phase I dose escalation safety and immunogenicity trial of Plasmodium falciparum apical membrane protein (AMA-1) FMP2.1, adjuvanted with AS02A, in malaria-naive adults at the Walter Reed Army Institute of Research. Vaccine 2007; 25:4203-4212.
47. Theisen M, Dodoo D, Toure-Balde A, et al. Selection of glutamate-rich protein long synthetic peptides for vaccine development: antigenicity and relationship with clinical protection and immunogenicity. Infect Immun 2001; 69:5223-5229.
48. Hermsen CC, Verhage DF, Telgt DS, et al. Glutamate-rich protein (GLURP) induces antibodies that inhibit in vitro growth of Plasmodium falciparum in a phase 1 malaria vaccine trial. Vaccine 2007; 25:2930-2940. This phase I trial with the long synthetic peptide GLURP [85-213 sequence (LR67)] showed the candidate to be safe and immunogenic, with high levels of (mainly cytophilic IgG1) antibodies that induced a dose-dependent inhibition of parasite growth in vitro in the presence of monocytes.
49. Li J, Matsuoka H, Mitamura T, Horii T. Characterization of proteases involved in the processing of Plasmodium falciparum serine repeat antigen (SERA). Mol Biochem Parasitol 2002; 120:177-186.
50. Pan W, Huang D, Zhang Q, et al. Fusion of two malaria vaccine candidate antigens enhances product yield, immunogenicity, and antibody-mediated inhibition of parasite growth in vitro. J Immunol 2004; 172:6167-6174.
51. Genton B, Pluschke G, Degen L, et al. A randomized placebo-controlled phase Ia malaria vaccine trial of two virosome-formulated synthetic peptides in healthy adult volunteers. PLoS Clin Trials (in press).
52. Okitsu SL, Silvie O, Westerfeld N, et al. A virosomally formulated malaria peptide vaccine elicits a long-lasting Plasmodium falciparum sporozoite-inhibitory antibody response in human volunteers. PLoS Clin Trials (in press).
53. Peek LJ, Brandau DT, Jones LS, et al. A systematic approach to stabilizing EBA-175 RII-NG for use as a malaria vaccine. Vaccine 2006; 24:5839-5851.
54. Pattnaik P, Shakri AR, Singh S, et al. Immunogenicity of a recombinant malaria vaccine based on receptor binding domain of Plasmodium falciparum EBA-175. Vaccine 2007; 25:806-813.
55. Arevalo-Herrera M, Castellanos A, Yazdani SS, et al. Immunogenicity and protective efficacy of recombinant vaccine based on the receptor-binding domain of the Plasmodium vivax Duffy binding protein in Aotus monkeys. Am J Trop Med Hyg 2005; 73:25-31.
56. Bull PC, Lowe BS, Kortok M, et al. Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria. Nat Med 1998; 4:358-360.
57. Ahuja S, Pettersson F, Moll K, et al. Induction of cross-reactive immune responses to NTS-DBL-1alpha/x of PfEMP1 and in vivo protection on challenge with Plasmodium falciparum. Vaccine 2006; 24:6140-6154.