Plasmodium vivax vaccine: What is the best way to go?

Abstract

Malaria is one of the most devastating human infectious diseases caused by Plasmodium spp. parasites. A search for an effective and safe vaccine is the main challenge for its eradication. Plasmodium vivax is the second most prevalent Plasmodium species and the most geographically distributed parasite and has been neglected for decades. This has a massive gap in knowledge and consequently in the development of vaccines. The most significant difficulties in obtaining a vaccine against P. vivax are the high genetic diversity and the extremely complex life cycle. Due to its complexity, studies have evaluated P. vivax antigens from different stages as potential targets for an effective vaccine. Therefore, the main vaccine candidates are grouped into preerythrocytic stage vaccines, blood-stage vaccines, and transmission-blocking vaccines. This review aims to support future investigations by presenting the main findings of vivax malaria vaccines to date. There are only a few P. vivax vaccines in clinical trials, and thus far, the best protective efficacy was a vaccine formulated with synthetic peptide from a circumsporozoite protein and Montanide ISA-51 as an adjuvant with 54.5% efficacy in a phase IIa study. In addition, the majority of P. vivax antigen candidates are polymorphic, induce strain-specific and heterogeneous immunity and provide only partial protection. Nevertheless, immunization with recombinant proteins and multiantigen vaccines have shown promising results and have emerged as excellent strategies. However, more studies are necessary to assess the ideal vaccine combination and test it in clinical trials. Developing a safe and effective vaccine against vivax malaria is essential for controlling and eliminating the disease. Therefore, it is necessary to determine what is already known to propose and identify new candidates.

Human sterile immunity to Plasmodium vivax malaria correlates with specific antibody response elicited by immunization with radiation-attenuated sporozoites

“…Taken together, these ndings contribute to understanding the antibody response to P. vivax infection, particularly to the correlates of protection. Deeper analyses are required for the identi cation of potential surrogate markers or signatures of immune protection using systems biology 5,30,60,61…”

“…Antibodies to several P. falciparum antigens identi ed in RAS immunization as probably associated with protection have been the subject of intense research on developing subunit vaccines 21,22,[25][26][27] . The recent approval of the P. falciparum RTS, S by WHO as well as the progress achieved by the Pf-R21/MM and, more recently, a PvCS formulation underscore the great value of subunit vaccines 4,21,[28][29][30] In contrast to P. falciparum, the overall progress in P. vivax vaccine development and the identi cation of antibodies against P. vivax has been limited to relatively few proteins made available through traditional cloning methods or peptide synthesis. Only a few of the ~ 5,500 genes encoded by the P. vivax genome have been studied as potential vaccine candidates.…”

“…Currently, only three P. vivax antigens, the circumsporozoite protein (PvCSP) 12,28,[31][32][33] , sexual-stage ookinete surface protein (Pvs25) 2,3,34 , and P. vivax Duffy-binding protein (PvDBP) 35 have reached vaccine clinical development phases (Phase Ia, Phase IIa/b). However, several others are in preclinical development and discovery phases 21,29,30,36,37 . Nevertheless, which of these are responsible for protection remains unclear.…”

Plasmodium vivax transcriptomics: What is new?

“…21,27,28 Therefore, the development of new vaccine targets and effective drugs to combat malaria is increasingly necessary. 27–29 In addition, vivax malaria has re-emerged in regions considered malaria free. 21,30,31…”

“…21,27,28 Therefore, the development of new vaccine targets and effective drugs to combat malaria is increasingly necessary. [27][28][29] In addition, vivax malaria has re-emerged in regions considered malaria free. 21,30,31 Among the Plasmodium species, P. vivax is most closely related to P. cynomolgi, the species responsible for infection in Asian monkeys.…”