Immunogenicity of a plasmid DNA vaccine encoding 42 kDa fragment of Plasmodium vivax merozoite surface protein-1

Sheikh, Inayat Hussain; Kaushal, Deep C.; Chandra, Deepak; Kaushal, Nuzhat A.

doi:10.1016/j.actatropica.2016.06.013

Cited by 5 publications

(4 citation statements)

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“…Thus, discovering a conserved pathway for parasite infection and subsequent development may provide a broad-spectrum target for interrupting pathogen transmission through mosquitoes. Antimalarial vaccine efforts have mainly focused on merozoite and sporozoite surface proteins (Neal et al, 2010;Yoshida et al, 2010;Alaro et al, 2013;Burns et al, 2016;Sheikh et al, 2016;Laurens, 2020). The RTS,S vaccine, based on P. falciparum circumsporozoite protein and introduced in 2019 (Laurens, 2020), is the only malaria vaccine available.…”

Section: Introductionmentioning

confidence: 99%

Targeting plasmodium α-tubulin-1 to block malaria transmission to mosquitoes

Zhang

Niu

Hooker–Romera

et al. 2023

Front. Cell. Infect. Microbiol.

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Plasmodium ookinetes use an invasive apparatus to invade mosquito midguts, and tubulins are the major structural proteins of this apical complex. We examined the role of tubulins in malaria transmission to mosquitoes. Our results demonstrate that the rabbit polyclonal antibodies (pAb) against human α-tubulin significantly reduced the number of P. falciparum oocysts in Anopheles gambiae midguts, while rabbit pAb against human β-tubulin did not. Further studies showed that pAb, specifically against P. falciparum α-tubulin-1, also significantly limited P. falciparum transmission to mosquitoes. We also generated mouse monoclonal antibodies (mAb) using recombinant P. falciparum α-tubulin-1. Out of 16 mAb, two mAb, A3 and A16, blocked P. falciparum transmission with EC50 of 12 μg/ml and 2.8 μg/ml. The epitopes of A3 and A16 were determined to be a conformational and linear sequence of EAREDLAALEKDYEE, respectively. To understand the mechanism of the antibody-blocking activity, we studied the accessibility of live ookinete α-tubulin-1 to antibodies and its interaction with mosquito midgut proteins. Immunofluorescent assays showed that pAb could bind to the apical complex of live ookinetes. Moreover, both ELISA and pull-down assays demonstrated that insect cell-expressed mosquito midgut protein, fibrinogen-related protein 1 (FREP1), interacts with P. falciparum α-tubulin-1. Since ookinete invasion is directional, we conclude that the interaction between Anopheles FREP1 protein and Plasmodium α-tubulin-1 anchors and orients the ookinete invasive apparatus towards the midgut PM and promotes the efficient parasite infection in the mosquito.

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Section: Introductionmentioning

confidence: 99%

Targeting plasmodium α-tubulin-1 to block malaria transmission to mosquitoes

Zhang

Niu

Hooker–Romera

et al. 2023

Front. Cell. Infect. Microbiol.

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“…Sheikh et al. ( 131 ) developed a plasmid DNA vaccine encoding a 42 kDa fragment of PvMSP-1. The immunogenicity of this vaccine was investigated by priming BALB/c mice either with the PvMSP-1 42 DNA plasmid or with recombinant PvMSP-1 42 protein and boosting with recombinant PvMSP-1 42 protein ( 131 ).…”

Section: Blood-stage Vaccinementioning

confidence: 99%

“…Sheikh et al (131) developed a plasmid DNA vaccine encoding a 42 kDa fragment of PvMSP-1. The immunogenicity of this vaccine was investigated by priming BALB/c mice either with the PvMSP-1 42 DNA plasmid or with recombinant PvMSP-1 42 protein and boosting with recombinant PvMSP-1 42 protein (131). The best immune response was induced by prime boosting with recombinant protein, which resulted in higher antibody and cytokine responses than the control and DNA alone, suggesting that the recombinant protein is essential for an improved immune response (131).…”

Section: Merozoite Surface Antigens 411 Pvmsp Familymentioning

confidence: 99%

“…The immunogenicity of this vaccine was investigated by priming BALB/c mice either with the PvMSP-1 42 DNA plasmid or with recombinant PvMSP-1 42 protein and boosting with recombinant PvMSP-1 42 protein (131). The best immune response was induced by prime boosting with recombinant protein, which resulted in higher antibody and cytokine responses than the control and DNA alone, suggesting that the recombinant protein is essential for an improved immune response (131). Kim et al (132) developed a vaccine formulation comprising attenuated Korea vaccinia virus (KVAC103) expressing the 33 kDa fragment of PvMSP-1.…”

Section: Merozoite Surface Antigens 411 Pvmsp Familymentioning

confidence: 99%

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

Veiga

Moriggi²,

Vettorazzi³

et al. 2023

Front. Immunol.

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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.

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