z-logo
Premium
Immunogenicity of malaria transmission‐blocking vaccine candidate, y230.CA14 following crosslinking in the presence of tetanus toxoid
Author(s) -
Vincent Arokia A.,
Fanning Sarah,
Caira Francesco C.,
Williamson Kim C.
Publication year - 1999
Publication title -
parasite immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 75
eISSN - 1365-3024
pISSN - 0141-9838
DOI - 10.1046/j.1365-3024.1999.00255.x
Subject(s) - biology , toxoid , immunogenicity , epitope , plasmodium falciparum , immune system , malaria vaccine , antibody , antigen , recombinant dna , microbiology and biotechnology , virology , immunology , biochemistry , immunization , malaria , gene
SUMMARY Proteolytically processed 310 kDa form of Plasmodium falciparum gamete surface antigen, Pfs230, is the target of malaria transmission‐blocking monoclonal antibodies. To design a recombinant malaria transmission‐blocking subunit vaccine, the amino terminus of the 310 kDa surface‐exposed form of Pfs230 was mapped to amino acids (aa) 522 and 584 using a series of peptides and recombinant proteins encoding distinct regions of Pfs230. Antiserum generated against an Escherichia coli ‐produced recombinant protein, spanning the Pfs230 processing site and extending into the cysteine domains, r230/MBP.C (aa 443–1132), reduced parasite infectivity by 71.2–89.8%. To determine if the region spanning the cleavage site blocked malaria transmission when produced as a secreted protein by Saccharomyces cerevisiae , y230.CA14 (aa 467–584) was generated, purified, emulsified in adjuvant and used to vaccinate mice. In contrast to E. coli ‐produced r230/MBP.C, the immune response generated against y230.CA14 was very weak. To enhance the response, y230.CA14 was mixed with tetanus toxoid, chemically crosslinked, repurifed, and its immunogenicty compared with unconjugated y230.CA14. Conjugated‐y230.CA14/TT required fewer booster injections to induce an immune response against Pfs230 and the antibodies generated reacted with the surface of intact gametes and immunoprecipitated radiolabelled Pfs230 extracted from 125 I surface‐labelled gametes to a greater extent. After seven injections, all y230.CA14 vaccinated mice developed anti‐Pfs230 antibodies and the isotype profile was the same. In addition to enhancing the initial immune response generated against y230.CA14, conjugation focuses the immune response toward epitopes within the region of Pfs230 present on the surface of the gamete.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here