N-Terminal Prodomain of Pfs230 Synthesized Using a Cell-Free System Is Sufficient To Induce Complement-Dependent Malaria Transmission-Blocking Activity

By M. Tachibana, Yimin Wu, H. Iriko, O. Muratova, N. MacDonald, J. Sattabongkot, S. Takeo, H. Otsuki, M. Torii, T. Tsuboi. 2011

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ABSTRACT The aim of a malaria transmission-blocking vaccine is to block the development of malaria parasites in the mosquito and thus prevent subsequent infection of the human host. Previous studies have demonstrated that the gametocyte/gamete surface protein Pfs230 can induce transmission-blocking immunity and have evaluated Escherichia coli-produced Pfs230 as a transmission-blocking vaccine candidate. In this study, we used the wheat germ cell-free expression system to produce N-terminal fragments of Pfs230 and evaluated the transmission-blocking activity of antisera raised against the recombinant Pfs230 protein. The rabbit antisera reacted to the surface of cultured gametocytes and gametes of the Plasmodium falciparum NF54 line, recognized the 360-kDa form of parasite-produced Pfs230 by Western blot assay, and reduced the infectivity of NF54 parasites to Anopheles stefensi mosquitoes in the presence of complement in a standard membrane feeding assay. Thus, our data demonstrate that the N-terminal pro domain of Pfs230 is sufficient to induce complement-dependent transmission-blocking activity against P. falciparum.

Subfields: Immunology, Public Health, Environmental and Occupational Health

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In Immunology

1. P. Duffy
2. Stefan H. I. Kappe

In Public Health, Environmental and Occupational Health

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2. Stefan H. I. Kappe
3. Silvia A. Arredondo

Citations in the corpus

• Structural and Immunological Characterization of Recombinant 6-Cysteine Domains of the Plasmodium falciparum Sexual Stage Protein Pfs230* (2016, background): “Various forms or domains of Pfs230 have been expressed in several recombinant expression systems, including Saccharomyces cerevisiae, Escherichia coli, plants, and wheat germ (9, 12, 13, 23) but to date none of the recombinant forms of Pfs230 have been suitable for extensive biochemical and biophysi”
• The s48/45 six-cysteine proteins: mediators of interaction throughout the Plasmodium life cycle (2016, background): “The analysis of 113 Pvs230 sequences from around the world showed that it also is under purifying selection with very low nucleotide diversity (Doi et al., 2011; Tachibana et al., 2011).”
• Identification of domains within Pfs230 that elicit transmission blocking antibody responses (2019, unknown): “In each experiment, anti-HisGST antibody was used as a negative control (TBV28), and anti-TBV27 mouse antibody was included as a positive control, as the same construct (called “Pfs230C”) specifically recognized Pfs230 and induced functional antibodies in the previous studies [11,12].”
• Plasmodium 6-Cysteine Proteins: Functional Diversity, Transmission-Blocking Antibodies and Structural Scaffolds (2022, background): “As such, a number of recombinant N-terminal fragments of Pfs230 are under investigation as vaccine candidates (Farrance et al., 2011; Tachibana et al., 2011; MacDonald et al., 2016; Lee et al., 2017; Chan et al., 2019; Wetzel et al., 2019; Miura et al., 2019; Lee et al., 2019a; Lee et al., 2019b; Co”