24 Banyal and ElangbamTable I: Malaria vaccines in clinical trialsStages Vaccine/antigen Research group Trial phasePre-erythrocytic RTS,S: Hybrid P. falciparum GSK / WRAIR/MVI Phase IIbStageCSPHBsAg particles + AS02adjuvantCSP C-ter peptide + Montanide Dictagen / Lausanne Univ Phase IbISA 720ICC-1132: Hybrid CSP Apovia/MVI Phase IImultiepitope-HBc VLPsDNA vaccines (including US Navy/ Vical Phase IMuStDO-5: CSP/LSA-1/LSA-3/EXP1/TRAP)Live recombinant FPV- or Ox<strong>for</strong>d Univ/ Oxxon/MVI Phase IbMVA-CSP + LSA-1 epitopeLive recombinant MVA- Ox<strong>for</strong>d Univ/Oxxon Phase Ibmultiepitope string + TRAPLive recombinant Ad-CSP Crucell/GSK/WRAIR/NIAID Phase IaOther live recombinant vaccines Ox<strong>for</strong>d Univ; NYU Preclinical(MVA, cold-adapted influenzavirus)-CSPLSA-3 (long peptides; Pasteur Institute/WRAIR/ GSK Phase Ialipopeptide;recombinant)LSA-1, SALSA, other Hawaii Biotech; Epimmune Preclinicalliver-stage antigensAsexual MSP-1 42 kD + AS02 GSK/WRAIR/MVI Phase Ib/ IIerythrocytic AMA-1 MVDU; NIAID Phase Ibstage PfCP 2.9: MSP-1-AMA-1 fusion Sec Military Med Univ Shanghai/protein (yeast) + Montanide Wanxing harmaceuticals/WHO Phase IISA 720Other MSP-1 derivatives NIAID; Hawaii Biotech; AECOM; Preclinical to(peptides, Salmonella or Univ Maryland Phase IBCG recombinants)MSP-3 long peptides Pasteur Institute/ AMANET/EMVI Phase IbGLURP long peptide EMVI/SSI Phase IMSP-3-GLURP hybrid long EMVI/SSI Phase Ipeptide + Montanide ISA 720MSP-4, -5 Monash PreclinicalCombination B: MSP-1, -2, Queensland Med Res Institute/ Phase IIRESA + MontanideWEHRISE36 Osaka Univ/Biken Phase IOther blood-stage antigens Various groups Preclinical(EBA-175,EBP2, MAEBL,RAP-2, EMP-1, DBL-á..)Sexual stage PfS25 (yeast) NIH Phase IPvS25 and other sexual-stage NIH PreclinicalantigensSource: www.who.int/vaccine_research/documents/en/status_table.pdf.
Malaria vaccine development25has shown great promise (Angov et al., 2003). Thisvaccine reconstituted with ASO2A, falciparum Mzprotein 1 (FMP-1)/ASO2A was found to be safe andimmunogenic in mice, rabbits and rhesus macaques.<strong>The</strong> safety and immunogenicity trial has beenconducted in malaria-naïve individuals. A Phase Isafety study in malaria-experienced Kenyan adultshas been completed and is scheduled to begin a Phase Istudy in children in malaria-endemic region ofwestern Kenya.A chimeric fusion of domain III of AMA-1 and the 19-kDa portion of MSP-1 called P. falciparum chimericprotein 2 (Pf CP-2.9) containing conserved portions ofboth proteins is also being developed (Genton andCorradin, 2002). Pf CP-2.9 expressed in Pichiapastoris has demonstrated good immunogenicity toboth portions of antigen in mice, rabbits and non-human primates. A preclinical trial showed itseffectiveness, and a Phase I trial in malaria-naïvehealthy adults with Montanide ISA720 <strong>for</strong>mulation isunder way that began in February 2006.polymorphism and polyclonal B-cell activation.Protection in endemic areas takes years to develop andthere is no clearly defined immune response that caneffectively protect against the disease. <strong>The</strong>re is alsothe need to develop novel adjuvants that can enhancethe cell-mediated immunity, and also <strong>for</strong> thedevelopment of novel vectors and vaccine<strong>for</strong>mulations that will produce optimal protectiveimmune responses. Some of the recent vaccine trialslike RTS, S which showed 58% efficacy against severedisease have given encouraging results. Malariavaccine development is at an exciting stage with anoptimistic outlook. Recent advances in understandingthe immune mechanisms and the volume ofin<strong>for</strong>mation generated from malaria parasite genomewould help in better understanding and identificationof critical antigens <strong>for</strong> vaccine development. Perhaps,given the complexity of the parasite, vaccine based onall or many antigens would be more effective than theone based on a single antigen.ACKNOWLEDGMENTS<strong>The</strong> idea of a multi-component vaccine against blood- Ms. N. Elangbam is grateful to University Grantsstage parasites was approached by Patarroyo and Commission, New Delhi, <strong>for</strong> financial assistance incolleagues with a synthetic peptide vaccine SPf66, the <strong>for</strong>m of a Junior Research Fellowship (Nationalcontaining sequence from MSP-1 and two other Eligibility Test).blood-stage antigens combined with CS protein(Patarroyo et al., 1987). <strong>The</strong> vaccine underwent fourREFERENCESPhase III clinical trials in different locations. Studies Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, Milman J,in Colombian adults and children (Valero et al., 1993) Mandomando I, Spiessens B, Guinovart C, Espasa M,Bassat Q, Aide P, O<strong>for</strong>i-Anyinam O, Navia MM, Corachanand in Tanzanian children (Alonso et al., 1994) gaveS, Ceuppens M, Dubois MC, Demoite MA, Dubovsky F,encouraging results but no significant protection was Menendez C, Tornieporth N, Ballou WR, Thompson R andobserved in studies in Gambian infants (D'Alessandro Cohen J. 2004. Efficacy of the RTS, S/AS02A vaccineet al., 1995) and in Thailand (Nosten et al., 1996).against Plasmodium falciparum infection and disease inyoung African children: randomized controlled trial. LancetSexual-stage vaccines: <strong>The</strong> third vaccine strategy is 364: 1411-1420.the development of a sexual-stage vaccine. 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Lancet 344: 1175-1181.with cholera toxin (CT) when used to immunize intranasallyinduced significant Th-2 type immune Angov E, Aufiero BM, Turgeon AM, Van Handenhove M,Ockenhouse CF, Kester KE, Walsh DS, McBride JS, Duboisresponse in mice and the antisera completely blockedMC, Cohen J, Haynes JD, Eckels KH, Heppner DG, Ballouparasite transmission (Arakawa et al., 2003).WR, Diggs CL and Lyon JA. 2003. Development and preclinicalCONCLUSIONS analysis of a Plasmodium falciparum Mz surfaceprotein-1 (42) malaria vaccine. Mol Biochem Parasitol 128:Immunity to malaria is complex and not clearly195-204.defined with the parasite exhibiting various Arakawa T, Tsuboi T, Kishimoto A, Sahabongkot J, Suwanabunimmunoevasive mechanisms like antigenic variation,N, Rungruang T, Matsumoto Y, Tsuji N, Hisaeda H, StowersA, Shimabukuro I, Sato Y and Torii M. 2003. Serum
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