<i>Plasmodium vivax</i>vaccine surrogate markers of protection: dawning of a new era

Galinski, Mary R.; Tirouvanziam, Rabindra; Moreno, Alberto

doi:10.2217/fmeb2013.13.193

Cited by 2 publications

(2 citation statements)

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“…Unlike P. falciparum , a long-term in vitro culture system for P. vivax does not currently exist due to the need for a regular supply of reticulocytes ( Noulin et al, 2013 ), and thus, we believe yet to be defined culture media components that better mimic the host environment are also needed (unpublished data). In the meantime, NHP models have been critical for generating P. vivax material for in-depth analyses ( Anderson et al, 2015 ) and NHP experimental studies continue to complement and expand upon blood-stage analyses that are now possible with small clinical samples attained from human infections ( Russell et al, 2012 ; Galinski et al, 2014 ).…”

Section: Nhp-malaria Models Overviewmentioning

confidence: 99%

“…Unlike human studies, experimental NHP model systems are well suited for studying LSFs and relapse biology. Future malaria research with non-human primates (NHPs) on these topics will undoubtedly include large-scale ‘omics,’ advanced immune profiling, mathematical modeling, computational biology, and the integration of clinical and ‘omics’ datasets ( Galinski et al, 2013 , 2014 ; Voit, 2013 ).…”

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confidence: 99%

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No more monkeying around: primate malaria model systems are key to understanding Plasmodium vivax liver-stage biology, hypnozoites, and relapses

2015

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Plasmodium vivax is a human malaria parasite responsible for significant morbidity worldwide and potentially death. This parasite possesses formidable liver-stage biology that involves the formation of dormant parasites known as hypnozoites. Hypnozoites are capable of activating weeks, months, or years after a primary blood-stage infection causing relapsing bouts of illness. Elimination of this dormant parasitic reservoir will be critical for global malaria eradication. Although hypnozoites were first discovered in 1982, few advancements have been made to understand their composition and biology. Until recently, in vitro models did not exist to study these forms and studying them from human ex vivo samples was virtually impossible. Today, non-human primate (NHP) models and modern systems biology approaches are poised as tools to enable the in-depth study of P. vivax liver-stage biology, including hypnozoites and relapses. NHP liver-stage model systems for P. vivax and the related simian malaria species P. cynomolgi are discussed along with perspectives regarding metabolite biomarker discovery, putative roles of extracellular vesicles, and relapse immunobiology.

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Section: Nhp-malaria Models Overviewmentioning

confidence: 99%

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confidence: 99%

No more monkeying around: primate malaria model systems are key to understanding Plasmodium vivax liver-stage biology, hypnozoites, and relapses

2015

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Immunogenicity of synthetic peptide constructs based on PvMSP9E795-A808, a linear B-cell epitope of the P. vivax Merozoite Surface Protein-9

Rodrigues-da-Silva

Correa-Moreira

Soares

et al. 2019

Vaccine

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Plasmodium vivax Merozoite Surface Protein-9 (PvMSP-9) is a malaria vaccine candidate naturally immunogenic in humans and able to induce high antibody titers in animals when delivered as a recombinant protein. Recently, we identified the sequence EAAPENAEPVHENA (PvMSP9 E795-A808) as the main linear B-cell epitope in naturally exposed individuals. However, the potential of PvMSP9 E795-A808 as an immunogen in experimental animal models remained unexplored. Here we assess the immunogenicity of PvMSP9 E795-A808 using synthetic peptides. The peptides tested in BALB/c mice include two repeats of the sequence EAAPENAEPVHENA tested alone (peptide RII), or linked to an autologous (PvMSP9 peptide pL; pLRII) or heterologous (p2 tetanus toxin universal T cell epitope; TTRII) T cell epitope. Immune responses were evaluated by ELISA, FLUOROSPOT, and indirect immunofluorescence. We show that all of the peptide constructs tested were immunogenic eliciting specific IgG antibodies at different levels, with a prevalence of IgG1 and IgG2. Animals immunized with synthetic peptides containing T cell epitopes (pLRII or TTRII) had more efficient antibody responses that resulted in higher antibody titers able to recognize the native protein by immunofluorescence. Relevantly, the frequency of IFN-c secreting SFC elicited by immunization with TTRII synthetic peptide was comparable to that reported to the PvMSP9-Nt recombinant protein. Taken together, our study indicates that PvMSP9 E795-A808 is highly immunogenic in mice and further studies to evaluate its value as promising vaccine target are warranted. Moreover, our study supports the critical role of CD4 T cell epitopes to enhance humoral responses induced by subunit based vaccines.

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Plasmodium vivaxvaccine surrogate markers of protection: dawning of a new era

Cited by 2 publications

References 67 publications

No more monkeying around: primate malaria model systems are key to understanding Plasmodium vivax liver-stage biology, hypnozoites, and relapses

No more monkeying around: primate malaria model systems are key to understanding Plasmodium vivax liver-stage biology, hypnozoites, and relapses

Immunogenicity of synthetic peptide constructs based on PvMSP9E795-A808, a linear B-cell epitope of the P. vivax Merozoite Surface Protein-9

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