Protective efficacy of peptides from Plasmodium vivax circumsporozoite protein

Atcheson, Erwan; Reyes-Sandoval, Arturo

doi:10.1016/j.vaccine.2020.03.063

Cited by 16 publications

(19 citation statements)

References 41 publications

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“…In previous studies, we generated two chimeric P. berghei parasites ( Pb-Pv CSP210 and Pb-Pv CSP247) that express the full-length VK210 and VK247 variants of P. vivax CSP on the spz surface 25 . These parasites have been used to analyze protective efficacy in mice immunized with different vaccine candidates targeting Pv CSP with an immunization-challenge mouse model 41 – 43 . To analyze protective immune responses induced by the two recombinant proteins NLP-CSP CT or NLP-CSP R against not only the VK210 and VK247 repeats but also against the P. vivax -like variant, we generated a third chimeric P. berghei parasite that expressed the Pv CSP- P. vivax -like protein in spz.…”

Section: Resultsmentioning

confidence: 99%

“…In particular, the use of transgenic parasites in the study of CSP-based vaccine formulations for the pre-erythrocytic phase of infection has allowed the analysis of functional inhibition of the exogenous CSP, expressed in replacement of the endogenous protein. Following this strategy, chimeric P. berghei parasites expressing the P. vivax CSP variants VK210 and VK247 were used to determine the protective efficacy of vaccine formulations consisting of viral vectors carrying P. vivax CSP alleles 25 , 41 – 43 . In this study, we generated for the first time a chimeric P. berghei parasite line expressing the third Pv CSP variant, Pv CSP- P. vivax -like.…”

Section: Discussionmentioning

confidence: 99%

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A universal vaccine candidate against Plasmodium vivax malaria confers protective immunity against the three PvCSP alleles

Gimenez

Salman

Marques

et al. 2021

Sci Rep

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Malaria is a highly prevalent parasitic disease in regions with tropical and subtropical climates worldwide. Among the species of Plasmodium causing human malaria, P. vivax is the second most prevalent and the most geographically widespread species. A major target of a pre-erythrocytic vaccine is the P. vivax circumsporozoite protein (PvCSP). In previous studies, we fused two recombinant proteins representing three allelic variants of PvCSP (VK210, VK247 and P. vivax-like) to the mumps virus nucleocapsid protein to enhance immune responses against PvCSP. The objective of the present study was to evaluate the protective efficacy of these recombinants in mice challenged with transgenic P. berghei parasites expressing PvCSP allelic variants. Formulations containing Poly (I:C) or Montanide ISA720 as adjuvants elicited high and long-lasting IgG antibody titers specific to each PvCSP allelic variant. Immunized mice were challenged with two existing chimeric P. berghei parasite lines expressing PvCSP-VK210 and PvCSP-VK247. We also developed a novel chimeric line expressing the third allelic variant, PvCSP-P. vivax-like, as a new murine immunization-challenge model. Our formulations conferred partial protection (significant delay in the time to reach 1% parasitemia) against challenge with the three chimeric parasites. Our results provide insights into the development of a vaccine targeting multiple strains of P. vivax.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A universal vaccine candidate against Plasmodium vivax malaria confers protective immunity against the three PvCSP alleles

Gimenez

Salman

Marques

et al. 2021

Sci Rep

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“…This underscores the potential of this extended region as a vaccine candidate and should be the focus of further study; although the efficacy conferred by individual peptides is low, extending vaccination to include all (and only) the disordered region of TRAP may be more protective, focusing the response on neutralising targets and away from immunogenic but antigenically non-protective regions of TRAP. It will also be of interest to try combining the immunodominant CD8 + T-cell epitope from PvTRAP with protective PvCSP repeat peptides 27 on a single immunodominant antigen, although research has shown that much higher doses of Qβ are required 28 .…”

Section: Discussionmentioning

confidence: 99%

Discovery of four new B-cell protective epitopes for malaria using Q beta virus-like particle as platform

et al. 2020

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Malaria remains one of the world’s most urgent global health problems, with almost half a million deaths and hundreds of millions of clinical cases each year. Existing interventions by themselves will not be enough to tackle infection in high-transmission areas. The best new intervention would be an effective vaccine; but the leading P. falciparum and P. vivax vaccine candidates, RTS,S and VMP001, show only modest to low field efficacy. New antigens and improved ways for screening antigens for protective efficacy will be required. This study exploits the potential of Virus-Like Particles (VLP) to enhance immune responses to antigens, the ease of coupling peptides to the Q beta (Qβ) VLP and the existing murine malaria challenge to screen B-cell epitopes for protective efficacy. We screened P. vivax TRAP (PvTRAP) immune sera against individual 20-mer PvTRAP peptides. The most immunogenic peptides associated with protection were loaded onto Qβ VLPs to assess protective efficacy in a malaria sporozoite challenge. A second approach focused on identifying conserved regions within known sporozoite invasion proteins and assessing them as part of the Qβ. Using this VLP as a peptide scaffold, four new protective B-cell epitopes were discovered: three from the disordered region of PvTRAP and one from Thrombospondin-related sporozoite protein (TRSP). Antigenic interference between these and other B-cell epitopes was also explored using the virus-like particle/peptide platform. This approach demonstrates the utility of VLPs to help identifying new B-cell epitopes for inclusion in next-generation malaria vaccines.

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“…In areas where drug resistance has been identi ed 27 , artemisinin combination therapy (ACT) is recommended, but the continuous increase and spread of resistance against anti-malarial drugs is of great concern in order to achieve the goal of eliminating malaria successful 28,29 . Moreover, VMP001, an advanced P. vivax' CSP-based malaria vaccine, has been reported to offers only lowest rate of protection against vivax malaria in humans 34 . There is currently no successful vaccine against malaria and only a small number of vaccines against P. vivax have been tested to date.…”

Section: Discussionmentioning

confidence: 99%

“…CSP has been identi ed to play a vital role in the maturation of sporozoite in the mosquito vector 31,32 . Plasmodium species conserve the CSP structure being an immunodominant B-cell epitope comprising of a central tandem portion anked by two non-repetitive domains containing proteolytic cleavage site and the thrombospondin repeat (TSR) at C-terminus 7,31,33 The protective e cacy of small peptide of allelic variants VK210 and VK247 of P. vivax CSP (PvCSP) has been reported as Qβ-peptide vaccine in order to provide minimal immunity for malaria 34 . The putative CSP of P. vivax plays a key role in coordinating protein degradation in P. vivax and can be used as a potential vaccine target, but extensive study needs to be carried out on this 30 .…”

Section: Introductionmentioning

confidence: 99%

Identification of Immunodominant Epitopes in Allelic Variants VK210 and VK247 of Pakistani based Plasmodium Vivax Circumsporozoite Immunogen

Naz¹,

Ahmad²,

Abbasi³

et al. 2021

Preprint

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Plasmodium vivax-induced malaria is one of the leading causes of morbidity and mortality in sub-tropical and tropical regions and known to infect 2.85 billion people globally. The continual rise and propagation of resistance against anti-malarial drugs is a prerequisite to identify a possible vaccine candidate for Plasmodium vivax (P. vivax). Circumsporozoite protein (CSP) is an important immunogen of malaria parasite that has conserved the CSP structure as an immune dominant B-cell epitope. In the current study, we focused on designing multi-epitope vaccines (MEVs) using various immunoinformatics tools against Pakistani based allelic variants VK210 and VK247 of P. vivax CSP (PvCSP) gene. Antigenicity, allergic potential and physicochemical parameters of both PvCSP variants were assessed for the designed MEVs and are within acceptable range suitable for post experimental investigations. The three-dimensional structures of both MEV shave been predicted ab initio, optimized, and validated by using different online servers. Structure and from residues perspectives, the MEVs are stable and are free from aggregation-prone regions. The stability of both MEVs has been improved by a disulfide engineering approach. To estimate the binding energy and stability of the MEVs, molecular docking simulation and binding free energy calculations with TLR-4 immune receptor have been conducted. The expression of both MEVs produced in Escherichia coli K12 expression system by in silico cloning was significant. Immune simulation revealed that the proposed MEVs induce strong humoral and cellular immunological responses, in addition to significant production of interleukins and cytokines. In conclusions, we believed that the MEVs proposed in current research, using combine approach of immunoinformatics, structural biology and biophysical approaches, could induce protective and effective immune responses against P. vivax and the experimental validation of our findings could contribute to the development of potential malaria vaccine.

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Protective efficacy of peptides from Plasmodium vivax circumsporozoite protein

Cited by 16 publications

References 41 publications

A universal vaccine candidate against Plasmodium vivax malaria confers protective immunity against the three PvCSP alleles

A universal vaccine candidate against Plasmodium vivax malaria confers protective immunity against the three PvCSP alleles

Discovery of four new B-cell protective epitopes for malaria using Q beta virus-like particle as platform

Identification of Immunodominant Epitopes in Allelic Variants VK210 and VK247 of Pakistani based Plasmodium Vivax Circumsporozoite Immunogen

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