PDF File - The Indian Society for Parasitology

22 Banyal and Elangbamand presence of anti Ro-GLURP antibodies in intense characteristic arrangement of cysteine containingmalaria transmission areas, and further that increasing domains within the proteins. Monoclonal antibodieslevels of IgG 1 and IgG 3 antibodies are associated against these proteins have been effective in blockingwith reducing P. falciparum parasite densities the infectivity of the parasites to mosquitoes(Lusingu et al., 2005). Erythrocyte membrane (Templeton and Kaslow, 1999). (ii) Ps 25 andproteins (EMP) e. g. EMP 1, 2 and 3 are also located on Ps 28 antigens. These are surface proteins expressederythrocyte membrane; however, Pf EMP-3 is on the zygotes and mature ookinetes of malariaexpressed not only on erythrocyte surface but also by parasite. The ookinete surface proteins of P.liver stage parasites and sporozoites (Gruner et al., falciparum, Pfs 25 and Pfs 28, are target antigens for a2001). possible vaccine and their homologous proteins haveParasite toxinsbeen cloned from P. vivax and other species. P.falciparum Pfs 25 has been tested in Phase I clinicalThe toxic basis of malarial pathogenesis was first trials in human volunteers (Kaslow and Shiloach,conjectured by Camillo Golgi in 1886 (Golgi, 1886). 1994). Yeast produced recombinant Pvs 25 and Pvs 28Malaria GPI is considered a candidate toxin as it are highly immunogenic and antisera recognizedinduces cytokine like TNF-α and adhesion expressioncorresponding molecules expressed by field-isolatedin macrophages and vascular endothelium which areparasites in Thailand (Sattabongkot et al., 2003).associated with malaria pathogenesis. Antibodies to CURRENT STATUS AND PROSPECTS OFGPI lipid domains have been associated with MALARIA VACCINESprotection against malaria. GPI is a highly conservedpro-inflammatory endotoxin of parasite origin and The development of a malaria vaccine remains ansynthetic anti-GPI can be used as a plausible anti-toxic urgent need for most people living in malaria endemicvaccine (Schofield et al. 2002).regions. Two lines of evidence suggest the feasibilitySexual stage antigensof a malaria vaccine: firstly, immunity can be acquiredas a result of natural exposure to infection, andVarious studies have demonstrated that antibodiessecondly, numerous experimental malaria infectionsdirected against the sexual-stage antigens can preventin animal models and human volunteers can befertilization in the mosquito thereby interrupting theprotected through various immunization strategies.transmission of malaria. Transmission blockingThe distinct developmental stages of malaria parasitevaccines (TBVs) would reduce or interrupt malariaprovide numerous targets for vaccine development.transmission in human and mosquito populationsBecause the production of live, attenuated or killed-within a community as a whole but confer noinactivated malaria vaccine is not practical, the aimprotection to an individual recipient. Such ahas been to develop sub-unit vaccines. In this, part ortransmission blocking vaccine when given incomplete antigens are identified from the pathogen'scombination with a pre-erythrocytic or blood-stageproteomic complement, which can induce protectivevaccine would prevent or reduce the spread ofimmunity to the whole pathogen on vaccination. Theparasites which become resistant to such vaccines andgeneral target for a subunit vaccine has been towould thus prolong the effective life of other malariaidentify critical target antigens at each stage of the life-vaccines. Antigens expressed on the surface of sexualcycle of malaria parasite. Another strategy is tostages i.e. gametocyte, gamete, zygote and ookinete ofassemble peptide sequences from a range of parasitemalaria parasite are being considered as promisingantigens into different combinations that are thentargets for developing a transmission blockingtested for immunogenicity in animal models andvaccine. These vaccines induce antibodies in humanhuman volunteers. In the new generation of DNA-host that inhibit parasite development withinbased subunit vaccines, DNA sequences from P.mosquito vector, thus, blocking parasite transmission.falciparum parasites have been inserted into plasmidCloning of genes and subsequent recombinantDNA molecules (DNA vaccines) or variousproteins have shown to induce transmission-blockingrecombinant attenuated DNA viruses (recombinantantibodies in animal models. Two groups of antigensviral vaccines) to generate candidate vaccines (Wanghave been explored to block the propagation of sexualet al., 1998). DNA vaccines are taken up by host cells,parasites. (i) Pfs 48/45 and Pfs 230 antigens. Theseprotein expressed and T-cells are primed to formproteins belong to a family unique to Plasmodium withmemory T-cell populations while in recombinant viral