Effects of transmission-blocking vaccines simultaneously targeting pre- and post-fertilization antigens in the rodent malaria parasite Plasmodium yoelii.

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  • Author(s): Zheng L;Zheng L; Pang W; Pang W; Qi Z; Qi Z; Luo E; Luo E; Cui L; Cui L; Cao Y; Cao Y
  • Source:
    Parasites & vectors [Parasit Vectors] 2016 Aug 08; Vol. 9 (1), pp. 433. Date of Electronic Publication: 2016 Aug 08.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 101462774 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-3305 (Electronic) Linking ISSN: 17563305 NLM ISO Abbreviation: Parasit Vectors Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central
    • Subject Terms:
      Antigens/*immunology ; Malaria/*prevention & control ; Malaria Vaccines/*immunology ; Plasmodium yoelii/*immunology ; Protozoan Proteins/*immunology; Animals ; Antigens/genetics ; Disease Models, Animal ; Female ; Immunization ; Malaria/immunology ; Malaria/parasitology ; Malaria/transmission ; Malaria Vaccines/administration & dosage ; Malaria Vaccines/genetics ; Male ; Mice ; Mice, Inbred BALB C ; Plasmodium yoelii/genetics ; Plasmodium yoelii/physiology ; Protozoan Proteins/administration & dosage ; Protozoan Proteins/genetics ; Reproduction
    • Abstract:
      Background: Transmission-blocking vaccine (TBV) is a promising strategy for interrupting the malaria transmission cycle. Current TBV candidates include both pre- and post-fertilization antigens expressed during sexual development of the malaria parasites.
      Methods: We tested whether a TBV design combining two sexual-stage antigens has better transmission-blocking activity. Using the rodent malaria model Plasmodium yoelii, we pursued a DNA vaccination strategy with genes encoding the gametocyte antigen Pys48/45 and the major ookinete surface protein Pys25.
      Results: Immunization of mice with DNA constructs expression either Pys48/45 or Pys25 elicited strong antibody responses, which specifically recognized a ~45 and ~25 kDa protein from gametocyte and ookinete lysates, respectively. Immune sera from mice immunized with DNA constructs expressing Pys48/45 and Pys25 individually and in combination displayed evident transmission-blocking activity in in vitro ookinete culture and direct mosquito feeding experiments. With both assays, the Pys25 sera had higher transmission-blocking activity than the Pys48/45 sera. Intriguingly, compared with the immunization with the individual DNA vaccines, immunization with both DNA constructs produced lower antibody responses against individual antigens. The resultant immune sera from the composite vaccination had significantly lower transmission-blocking activity than those from Pys25 DNA immunization group, albeit the activity was substantially higher than that from the Pys48 DNA vaccination group.
      Conclusions: This result suggested that vaccination with the two DNA constructs did not achieve a synergistic effect, but rather caused interference in inducing antigen-specific antibody responses. This result has important implications for future design of composite vaccines targeting different sexual antigens.
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    • Grant Information:
      R01 AI099611 United States AI NIAID NIH HHS
    • Contributed Indexing:
      Keywords: DNA vaccine; Malaria; Plasmodium yoelii; Pys25; Pys48/45; Transmission-blocking vaccine
    • Accession Number:
      0 (Antigens)
      0 (Malaria Vaccines)
      0 (Protozoan Proteins)
      0 (fertilization antigen)
    • Publication Date:
      Date Created: 20160810 Date Completed: 20171214 Latest Revision: 20181113
    • Publication Date:
      20250114
    • Accession Number:
      PMC4977633
    • Accession Number:
      10.1186/s13071-016-1711-2
    • Accession Number:
      27502144