**3.2** *Plasmodium vivax*

The increasing recognition of the importance of *Plasmodium vivax*, both as a significant cause of severe malaria and as a major obstacle to malaria control and elimination has exposed some major gaps in our knowledge of this parasite [182]. The vaccine development pipeline is lagging well behind that of *P.falciparum* and while work is progressing on vaccines targeted at the *P.vivax* Duffy-binding protein (DBP, [183]), which has long had a human genetic correlate (Duffy negative individuals have a greatly reduced risk of infection) [184], relatively little has been done on the blood-stage antigens homologous to those being intensively tested for *P.falciparum* [39]. Underlying this lack of development is an urgent need to understand more about the biology of the transmission of the parasite, the extent of its diversity at a population level, and the mechanism of acquiring immunity to it.

One major obstacle impeding *P.vivax* research is the fact that presently, *P.vivax* cannot be maintained in long-term culture or at high parasitaemias. In addition, infected individuals typically present with low parasitemia and therefore parasite material is less available than for *P. falciparum* [185]. Recombinant *P.vivax* proteins for use in immunoepidemiological studies and vaccine development therefore are often isolated from reference strains, such as Sal1 (Salvador).

Many *P. vivax* vaccine candidates currently being investigated are orthologues of *P. falciparum* vaccine candidate antigens [38, 39]. However, these two species have distinct biological features, the most obvious being the ability of *P. vivax* to form dormant liver stages, and also their variable transmission in different regions across the globe. Therefore it is difficult to base conclusions for *P.vivax*, on what is known for *P.falciparum*. Many experts believe that a malaria vaccine will need to contain a combination of both *P. falciparum* and *P. vivax* antigens to be globally effective, since many regions of the world are burdened with both species [38].

Only two *P.vivax* vaccine candidates, the circumsporozoite surface protein (CSP) and the gametocyte antigen, Pvs25, have been tested in clinical trials to date [38]. However, a host of additional *P.vivax* proteins are currently under investigation as potential vaccine candidates, including PvDBP [38], PvTRAP [186], PvMSP-1 [187], PvAMA-1 [188]; and the transmission blocking candidate, Pvs28 [38]. Additional antigens identified as potential *P.vivax* vaccine candidates include PvMSP3, PvMSP4, PvMSP5 and PvRBPs I and II [38]. PvMSP9 has also been revealed as a promising vaccine candidate in recent studies [189].
