Alternative Invasion Mechanisms and Host Immune Response to Plasmodium vivax Malaria: Trends and Future Directions

Kepple, Daniel; Pestana, Kareen; Tomida, Junya; Abebe, Abnet; Golassa, Lemu; Lo, Eugenia

doi:10.3390/microorganisms9010015

Cited by 18 publications

(18 citation statements)

References 187 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in recent years, it has been demonstrated that Duffy-negative individuals can be infected by P. vivax . This is probably due to other molecules involved in reticulocyte invasion, suggesting that the invasion mechanism is much more complex than believed ( 170 – 173 ).…”

Section: Blood-stage Vaccinementioning

confidence: 98%

See 1 more Smart Citation

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

Veiga

Moriggi²,

Vettorazzi³

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

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.

show abstract

Section: Blood-stage Vaccinementioning

confidence: 98%

“…Some RBPs, localized at the apical pole of merozoites, are possibly involved in the alternative invasion pathway of Duffy-negative individuals since they can bind to erythrocytes and have reticulocyte selectivity ( 172 , 173 , 193 , 194 ). Each protein has one specific binding site different from PvDBP.…”

Section: Blood-stage Vaccinementioning

confidence: 99%

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

Veiga

Moriggi²,

Vettorazzi³

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…These DBP vaccine efforts follow a body of research showing the importance of the Duffy glycoprotein on the surface of RBCs [ 41 ] as a receptor for the P. vivax DBP, which is located at the front (apical) end of the merozoite and is known to specifically attach to the cognate RBC receptor prior to invading the host RBC [ 299 , 302 – 304 ]. Complicating the situation, in the ensuing years, through research in multiple locales, it has become apparent that P. vivax can also invade Duffy negative RBCs by utilizing alternate invasion mechanisms (reviewed in [ 305 , 306 ]).…”

Section: Twenty-first Century—turning Point In Malaria Researchmentioning

confidence: 99%

Systems biology of malaria explored with nonhuman primates

Galinski

2022

Malar J

View full text Add to dashboard Cite

Abstract“The Primate Malarias” book has been a uniquely important resource for multiple generations of scientists, since its debut in 1971, and remains pertinent to the present day. Indeed, nonhuman primates (NHPs) have been instrumental for major breakthroughs in basic and pre-clinical research on malaria for over 50 years. Research involving NHPs have provided critical insights and data that have been essential for malaria research on many parasite species, drugs, vaccines, pathogenesis, and transmission, leading to improved clinical care and advancing research goals for malaria control, elimination, and eradication. Whilst most malaria scientists over the decades have been studying Plasmodium falciparum, with NHP infections, in clinical studies with humans, or using in vitro culture or rodent model systems, others have been dedicated to advancing research on Plasmodium vivax, as well as on phylogenetically related simian species, including Plasmodium cynomolgi, Plasmodium coatneyi, and Plasmodium knowlesi. In-depth study of these four phylogenetically related species over the years has spawned the design of NHP longitudinal infection strategies for gathering information about ongoing infections, which can be related to human infections. These Plasmodium-NHP infection model systems are reviewed here, with emphasis on modern systems biological approaches to studying longitudinal infections, pathogenesis, immunity, and vaccines. Recent discoveries capitalizing on NHP longitudinal infections include an advanced understanding of chronic infections, relapses, anaemia, and immune memory. With quickly emerging new technological advances, more in-depth research and mechanistic discoveries can be anticipated on these and additional critical topics, including hypnozoite biology, antigenic variation, gametocyte transmission, bone marrow dysfunction, and loss of uninfected RBCs. New strategies and insights published by the Malaria Host–Pathogen Interaction Center (MaHPIC) are recapped here along with a vision that stresses the importance of educating future experts well trained in utilizing NHP infection model systems for the pursuit of innovative, effective interventions against malaria.

show abstract

“…This action raises important issues concerning how P. vivax enters the erythrocytes of Duffy-negative individuals. It has been hypothesized that copy number variation, which is either low expression of DARC in Duffy-negative individuals, binds easily to parasites that carry multiple copies of P. vivax Duffy binding protein (PvDBP), changes in PvDBP1 or duplication in the PvDBP gene created a new entryway and is responsible for the parasites' increased ability to spread [ 97 , 155 ]. Due to this, it is challenging to control and eradicate P. vivax malaria, which highlights the concern that these 'new' P. vivax strains that infect Duffy-negative hosts could spread throughout much of Africa and have severe, significant effects on the general public health and economy.…”

Section: Control Challengesmentioning

confidence: 99%

Plasmodium vivax: the potential obstacles it presents to malaria elimination and eradication

Habtamu

Petros

Yan

2022

Trop Dis Travel Med Vaccines

View full text Add to dashboard Cite

Initiatives to eradicate malaria have a good impact on P. falciparum malaria worldwide. P. vivax, however, still presents significant difficulties. This is due to its unique biological traits, which, in comparison to P. falciparum, pose serious challenges for malaria elimination approaches. P. vivax's numerous distinctive characteristics and its ability to live for weeks to years in liver cells in its hypnozoite form, which may elude the human immune system and blood-stage therapy and offer protection during mosquito-free seasons. Many malaria patients are not fully treated because of contraindications to primaquine use in pregnant and nursing women and are still vulnerable to P. vivax relapses, although there are medications that could radical cure P. vivax. Additionally, due to CYP2D6's highly variable genetic polymorphism, the pharmacokinetics of primaquine may be impacted. Due to their inability to metabolize PQ, some CYP2D6 polymorphism alleles can cause patients to not respond to treatment. Tafenoquine offers a radical treatment in a single dose that overcomes the potentially serious problem of poor adherence to daily primaquine. Despite this benefit, hemolysis of the early erythrocytes continues in individuals with G6PD deficiency until all susceptible cells have been eliminated. Field techniques such as microscopy or rapid diagnostic tests (RDTs) miss the large number of submicroscopic and/or asymptomatic infections brought on by reticulocyte tropism and the low parasitemia levels that accompany it. Moreover, P. vivax gametocytes grow more quickly and are much more prevalent in the bloodstream. P. vivax populations also have a great deal of genetic variation throughout their genome, which ensures evolutionary fitness and boosts adaptation potential. Furthermore, P. vivax fully develops in the mosquito faster than P. falciparum. These characteristics contribute to parasite reservoirs in the human population and facilitate faster transmission. Overall, no genuine chance of eradication is predicted in the next few years unless new tools for lowering malaria transmission are developed (i.e., malaria elimination and eradication). The challenging characteristics of P. vivax that impede the elimination and eradication of malaria are thus discussed in this article.

show abstract

Alternative Invasion Mechanisms and Host Immune Response to Plasmodium vivax Malaria: Trends and Future Directions

Cited by 18 publications

References 187 publications

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

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

Systems biology of malaria explored with nonhuman primates

Plasmodium vivax: the potential obstacles it presents to malaria elimination and eradication

Contact Info

Product

Resources

About