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.

A Pvs25 mRNA vaccine induces complete and durable transmission-blocking immunity to Plasmodium vivax

“…Here, our results demonstrated that a nucleoside-modified mRNA–LNP vaccine encoding Pvs25 can induce cellular as well as durable antigen-specific antibody responses with potent parasite transmission-blocking activity in mice, providing strong support for further preclinical testing in nonhuman primates. Given the positive results, it seems worthwhile to apply the mRNA–LNP platform to other P. vivax vaccine antigen candidates 49 and potentially evaluate multivalent P. vivax mRNA–LNP vaccine formulations as successfully shown for influenza virus 50 – 53 . The platform has the potential to overcome the challenges of poor immunogenicity, strong reactogenicity, low potency, and short-lived immunity.…”

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…”

“…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.…”