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Comparative immunization study using RNA and DNA constructs encoding a part of the Plasmodium falciparum antigen Pf332
Stockholm University, Faculty of Science, Wenner-Gren Institute for Experimental Biology.
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2001 In: Scandinavian Journal of Immunology, ISSN 0300-9475, Vol. 54, no 1-2, 117-24 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2001. Vol. 54, no 1-2, 117-24 p.
URN: urn:nbn:se:su:diva-22913OAI: diva2:189729
Part of urn:nbn:se:su:diva-1263Available from: 2006-09-21 Created: 2006-09-21Bibliographically approved
In thesis
1. Vaccine development strategies applied to the Plasmodium falciparum malaria antigen 332
Open this publication in new window or tab >>Vaccine development strategies applied to the Plasmodium falciparum malaria antigen 332
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Malaria is one of the major infectious diseases in the world with regard to mortality and morbidity, and the development of a vaccine against the malaria parasite Plasmodium falciparum is considered of high priority. The aim of the work presented in this thesis was to develop and characterize recombinant vaccine constructs based on the P. falciparum asexual blood-stage antigen Pf332. We have studied the humoral responses in mice elicited by various types of constructs, including naked DNA plasmids, naked mRNA, alphavirus, and peptides. Immunological memory was successfully induced against the repetitive EB200 fragment of Pf332, although the antibody titers were generally low and the highest titers were unexpectedly obtained with a conventional DNA plasmid. In another study, we also demonstrated the ability to circumvent genetically restricted immune responses in mice against two malaria epitopes, one of them derived from Pf332, by inclusion of universal T-cell epitopes into multiple antigen peptide constructs. However, the overall variability of the responses stressed the importance of including several epitopes in a future malaria vaccine. Further, the recent completion of sequencing of Pf332 enabled us to identify and characterize the immunogenic properties of a non-repeat fragment of the Pf332, termed C231. Our analyses of C231 showed that antibodies raised against the recombinant protein possess an in vitro parasite inhibitory capacity similar to that of antibodies against recombinant EB200. Furthermore, the recognition of C231 by antibodies in sera from individuals naturally primed to P. falciparum, correlated well with that previously observed for the corresponding sera and EB200. When analyzing the IgG subclass distribution of anti-C231 antibodies, we noted a bias towards IgG2 and IgG3 relative to IgG1, differing from the subclass profiles of IgG binding crude P. falciparum antigen, which were dominated by IgG1. Taken together, the work presented herein is likely to facilitate further studies on Pf332 as a potential target for protective immune responses, and amounts to a small step towards the realization of a malaria vaccine.

Place, publisher, year, edition, pages
Stockholm: Wenner-Grens institut för experimentell biologi, 2006. 67 p.
malaria, sub-unit vaccines, immunogenicity, antibody response, antigen Pf332
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urn:nbn:se:su:diva-1263 (URN)91-7155-231-6 (ISBN)
Public defence
2006-10-13, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 8 C, Stockholm, 10:00
Available from: 2006-09-21 Created: 2006-09-21 Last updated: 2011-08-22Bibliographically approved

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