Evidences of protection against blood-stage infection of Plasmodium falciparum by the novel protein vaccine SE36

Horii, Toshihiro; Shirai, Hideaki; Li, Jie; Ishii, Ken J.; Palacpac, Nirianne; Tougan, Takahiro; Hato, Mariko; Ohta, Nobuo; Bobogare, Albino; Arakaki, Nana; Matsumoto, Yoshitsugu; Namazue, Junko; Ishikawa, Takahiro; Ueda, Shigeharu; Takahashi, Michiaki

doi:10.1016/j.parint.2010.05.002

Cited by 63 publications

(119 citation statements)

References 24 publications

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“…To date, research in this field has focused on a few protein candidates including merozoite surface protein (MSP)-1 (14), MSP-2 (8), MSP-3 (15)(16)(17)(18), apical membrane Ag 1 (AMA-1) (19), erythrocyte binding Ag 175 (EBA-175) (20), glutamate-rich protein (GLURP) (15,21), and serine repeat Ag 5 (SERA5) (22). These Ags are all merozoite proteins, either located on the merozoite surface or contained within apical invasion organelles.…”

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confidence: 99%

Passive Immunoprotection of Plasmodium falciparum-Infected Mice Designates the CyRPA as Candidate Malaria Vaccine Antigen

Dreyer

Matile

Papastogiannidis

et al. 2012

The Journal of Immunology

114

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An effective malaria vaccine could prove to be the most cost-effective and efficacious means of preventing severe disease and death from malaria. In an endeavor to identify novel vaccine targets, we tested predicted Plasmodium falciparum open reading frames for proteins that elicit parasite-inhibitory Abs. This has led to the identification of the cysteine-rich protective Ag (CyRPA). CyRPA is a cysteine-rich protein harboring a predicted signal sequence. The stage-specific expression of CyRPA in late schizonts resembles that of proteins known to be involved in merozoite invasion. Immunofluorescence staining localized CyRPA at the apex of merozoites. The entire protein is conserved as shown by sequencing of the CyRPA encoding gene from a diverse range of P. falciparum isolates. CyRPA-specific mAbs substantially inhibited parasite growth in vitro as well as in a P. falciparum animal model based on NOD-scid IL2Rγnull mice engrafted with human erythrocytes. In contrast to other P. falciparum mouse models, this system generated very consistent results and evinced a dose-response relationship and therefore represents an unprecedented in vivo model for quantitative comparison of the functional potencies of malaria-specific Abs. Our data suggest a role for CyRPA in erythrocyte invasion by the merozoite. Inhibition of merozoite invasion by CyRPA-specific mAbs in vitro and in vivo renders this protein a promising malaria asexual blood-stage vaccine candidate Ag.

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confidence: 99%

Passive Immunoprotection of Plasmodium falciparum-Infected Mice Designates the CyRPA as Candidate Malaria Vaccine Antigen

Dreyer

Matile

Papastogiannidis

et al. 2012

The Journal of Immunology

114

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“…The region represents a tandem repeat and it has been reported that proteins with repeats are immunogenic and effective in clearance mechanisms (Horii et al, 2010). In this study, the repeat region of sheath protein Shp-1 was cloned, expressed and its reactivity in filarial clinical population was evaluated.…”

Section: Discussionmentioning

confidence: 99%

Repeat region of Brugia malayi sheath protein (Shp-1) carries Dominant B epitopes recognized in filarial endemic population

Jawaharlal

Madhumathi

Prince

et al. 2014

Acta Parasitologica

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Transmission of lymphatic filariasis is mediated through microfilariae (L1 stage of the parasite) which is encased in an eggshell called sheath. The sheath protein Shp-1 stabilizes the structure due to the unique repeat region with Met-Pro-Pro-Gln-Gly sequences. Microfilarial proteins could be used as transmission blocking vaccines. Since the repeat region of Shp-1 was predicted to carry putative B epitopes, this region was used to analyze its reactivity with clinical samples towards construction of peptide vaccine. In silico analysis of Shp-1 showed the presence of B epitopes in the region 49-107. The polypeptide epitopic region Shp-1 49-107 was cloned and expressed in Escherichia coli. Antibody reactivity of the Shp-1 49-107 construct was evaluated in filarial endemic population by ELISA. Putatively immune endemic normals (EN) showed significantly high reactivity (P < 0.05) when compared to all the other categories. Antibody reactivity of Shp-1 repeat region was similar to that of whole protein proving that this region carries B epitopes responsible for its humoral response in humans. Thus this can be employed for inducing anti-microfilarial immunity in the infected population that may lead to reduction in transmission intensity and also it could be used along with other epitopes from different stages of the parasite in order to manage the disease effectively.

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“…However, sero-positivity rate against the Nterminal domain of P. falciparum SERA5 was observed to be relatively low (Fig. 11.; Aoki et al, 2002;Horii et al, 2010). Fig.…”

Section: Conclusion and Open Issues In Sera Studymentioning

confidence: 98%

“…Parasite egress from the host cell is an important process that remains poorly understood. P. falciparum SERA5 is a vaccine candidate molecule now on clinical trial in Uganda (Horii et al, 2010). Serum antibodies against the N-terminal domain of P. falciparum SERA5 in individuals living in malaria endemic area protect infants from clinical malaria and inhibit in vitro parasite growth (Okech et al, 2001(Okech et al, , 2006Aoki et al, 2002;Horii et al, 2010).…”

Section: Conclusion and Open Issues In Sera Studymentioning

confidence: 99%

“…Some SERA genes were confirmed to play essential role(s) in the parasite life cycle (Miller et al, 2002;Aly & Matuschewski, 2005;McCoubrie et al, 2007). In addition, a gene family member in P. falciparum, SERA5, is a vaccine candidate now on phase Ib clinical trial (Horii et al, 2010). Two observations promise SERA5 as a vaccine candidate: (1) SERA genes are not differently expressed like other antigen encoding gene families such as var and rifin that show antigenic variation to evade host immune response (Aoki et al, 2002;Miller et al, 2002;Palacpac et al, 2006;Schmidt-Christensen et al, 2008;Putrianti et al, 2010;Arisue et al, 2011); and (2) P. falciparum SERA5 is less polymorphic (Fox et al, 1997: Morimatsu et al, 1997Liu et al, 2000) than other vaccine candidate genes such as merozoite surface protein 1 (McBride et al, 1985) and apical membrane protein 1 (Polley et al, 2003;Cortés et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Clues to Evolution of the SERA Multigene Family in the Genus Plasmodium

Arisue¹,

Palacpac²,

Tanabe³

et al. 2011

Gene Duplication

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Evidences of protection against blood-stage infection of Plasmodium falciparum by the novel protein vaccine SE36

Cited by 63 publications

References 24 publications

Passive Immunoprotection of Plasmodium falciparum-Infected Mice Designates the CyRPA as Candidate Malaria Vaccine Antigen

Passive Immunoprotection of Plasmodium falciparum-Infected Mice Designates the CyRPA as Candidate Malaria Vaccine Antigen

Repeat region of Brugia malayi sheath protein (Shp-1) carries Dominant B epitopes recognized in filarial endemic population

Clues to Evolution of the SERA Multigene Family in the Genus Plasmodium

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