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Immunogenicity and antigenic properties of Pf332-C231, a fragment of a non-repeat region of the Plasmodium falciparum antigen Pf332
Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
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2009 (English)In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 28, no 1, 90-97 p.Article in journal (Refereed) Published
Abstract [en]

Antigen Pf332, a megadalton protein has been shown to be associated with the membrane of infected erythrocytes. Detailed functional studies on the antigen have remained hampered by the cross-reactive nature of antibodies generated to Pf332. Pf332-C231, identified in the C-terminal region of Pf332 was cloned and antibodies against the C231 fragment were shown to react with intact Pf332 antigen by both immunofluorescence and immunoblotting analyses. Antibodies to C231 inhibited in vitro Plasmodium falciparum growth efficiently. In addition, human sera from malaria-exposed individuals reacted with recombinant C231. We show that Pf332-C231 represents a functional domain and is expected to facilitate further studies on Pf332 as a potential target for protective immune responses and the function of the antigen.

Place, publisher, year, edition, pages
2009. Vol. 28, no 1, 90-97 p.
Keyword [en]
Plasmodium falciparum, Pf332-C231, Growth inhibition
National Category
Immunology
Research subject
Immunology
Identifiers
URN: urn:nbn:se:su:diva-32902DOI: 10.1016/j.vaccine.2009.09.110ISI: 000274869200012PubMedID: 19822232OAI: oai:DiVA.org:su-32902DiVA: diva2:281914
Available from: 2009-12-17 Created: 2009-12-17 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Immunological characteristics of recombinant fragments of the Plasmodium falciparum blood-stage antigen Pf332
Open this publication in new window or tab >>Immunological characteristics of recombinant fragments of the Plasmodium falciparum blood-stage antigen Pf332
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Effective malaria vaccine might help improve control strategies against malaria, but the complexity of interactions between the parasite and its hosts poses challenges. The asexual blood stage P. falciparum antigen Pf332 has potentials as one of the proteins in understanding the complex host-parasite interactions. The interest in Pf332 as a target for parasite neutralizing antibodies, evolved from previous studies demonstrating that Pf332-reactive antibodies inhibits parasite growth in vitro. The presence of natural P. falciparum infection also indicated that Pf332 has the ability to induce protective antibodies.

In paper I, we identified and characterized the immunogenicity of a C-terminal region of Pf332. Immunological analyses carried out with this fragment revealed that rabbit anti-C231 antibodies possess parasite in vitro inhibitory capabilities. In paper II, the functional activity of C231 specific antibodies was confirmed with human-affinity purified antibodies, where the antibodies inhibited late stage parasite development, by the presence of abnormal parasites and disintegrated red cell membranes.

Epidemiological data from malaria endemic area of Senegal (Paper III & IV), showed that antibodies were reactive with two different fragments of Pf332 (C231 and DBL). Distribution of anti-C231 antibodies in the IgG subclasses, gave similar levels of IgG2 and IgG3. The levels of anti-C231 antibodies were associated with protection from clinical malaria, but with DBL reactive antibodies IgG3 was associated with protection from clinical malaria.

We hereby conclude that antigen Pf332 contains immunogenic epitopes, and is a potential target for parasite neutralizing antibodies. The Pf332 protein should thus be considered as a candidate antigen for inclusion in a subunit P. falciparum malaria vaccine.

Place, publisher, year, edition, pages
Stockholm: The Wenner-Gren Institute, Stockholm University, 2011. 82 p.
Keyword
Plasmodium falciparum, Pf332, antibodies, immunity, growth inhibition
National Category
Immunology in the medical area
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-60540 (URN)978-91-7447-347-6 (ISBN)
Public defence
2011-09-22, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
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Note
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Submitted. Paper 4: Manuscript. Available from: 2011-08-31 Created: 2011-08-19 Last updated: 2011-08-22Bibliographically approved

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