Transmission of malaria parasites from humans to Anopheles mosquitoes can be inhibited by specific antibodies elicited during malaria infection, which target surface Plasmodium gametocyte/gamete proteins. Some of these proteins may have potential for vaccine development. Pvs48/45 is a P. vivax gametocyte surface antigen orthologous to Pfs48/45, which may play a role during parasite fertilization and thus has potential for transmission blocking (TB) activity. Here we describe the expression of a recombinant Pvs48/45 protein expressed in Escherichia coli as a ∼60kDa construct which we tested for antigenicity using human sera and for its immunogenicity and transmission blocking activity of specific anti-mouse and anti-monkey Pvs48/45 antibodies. The protein reacted with sera of individuals from malaria-endemic areas and in addition induced specific IgG antibody responses in BALB/c mice and Aotus l. griseimembra monkeys. Sera from both immunized animal species recognized native P. vivax protein in Western blot (WB) and immunofluorescence assays. Moreover, sera from immunized mice and monkeys produced significant inhibition of parasite transmission to An. Albimanus mosquitoes as shown by membrane feeding assays. Results indicate the presence of reactive epitopes in the Pvs48/45 recombinant product that induce antibodies with TB activity. Further testing of this protein is ongoing to determine its vaccine potential.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361554PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0119335PLOS

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Gamete surface protein P48/45 has been shown to be important for male gamete fertility and a strong candidate for the development of a malaria transmission-blocking vaccine (TBV). However, TBV development for homolog Pvs48/45 has been slow because of a number of challenges: availability of conformationally suitable recombinant protein; the lack of an challenge model; and the inability to produce gametocytes in culture to test transmission-blocking activity of antibodies. To support ongoing efforts to develop Pvs48/45 as a potential vaccine candidate, we initiated efforts to develop much needed reagents to move the field forward.

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Article Synopsis
  • Pvs48/45 is a Plasmodium vivax protein linked to parasite fertilization, and previous studies found it to be immunogenic in animal models; this study compares its immunogenicity in different vaccine formulations.
  • Recombinant Pvs48/45 proteins were produced in E. coli and CHO cells, combined with various adjuvants to immunize mice, and serum was analyzed for antibody responses and effectiveness in blocking parasite transmission.
  • Results indicated that while all adjuvants elicited antibody responses, Montanide ISA-51 with CHO-rPvs48/45 produced the strongest and most durable antibody levels, demonstrating the best transmission-blocking capability against the malaria parasite.
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Article Synopsis
  • P48/45 is a key gametocyte antigen related to malaria parasite fertilization, and a recombinant version of the protein expressed in CHO cells was tested for its immunogenic properties.
  • In studies with plasma from individuals in Colombia and Guatemala, the CHO-48/45 protein showed higher seroprevalence and stronger immune responses compared to another recombinant protein.
  • The research indicated that antibodies generated from CHO-48/45 could effectively block malaria transmission, suggesting its potential as a candidate for a malaria vaccine.
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Functional Conservation of P48/45 Proteins in the Transmission Stages of (Human Malaria Parasite) and .  (Murine Malaria Parasite).

mBio

September 2018

Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA

Sexual-stage proteins have a distinct function in the mosquito vector during transmission and also represent targets for the development of malaria transmission-blocking vaccine. P48/45, a leading vaccine candidate, is critical for male gamete fertility and shows >50% similarity across various species of We evaluated functional conservation of P48/45 in and with the motivation to establish transgenic strains expressing P48/45 (Pvs48/45) in an assay to evaluate the transmission-blocking activity of antibodies elicited by Pvs48/45. Homologous recombination was employed to target / (/) for knockout (KO) or for its replacement by two different forms of / (/) (the full-length gene and a chimeric gene consisting of / 5' signal and 3' anchor sequences flanking /).

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