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Immunological characteristics of recombinant fragments of the Plasmodium falciparum blood-stage antigen Pf332
Stockholm University, Faculty of Science, The Wenner-Gren Institute . (Kavs Berzins, Malaria Group)
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 [en]
Plasmodium falciparum, Pf332, antibodies, immunity, growth inhibition
National Category
Immunology in the medical area
Research subject
Immunology
Identifiers
URN: urn:nbn:se:su:diva-60540ISBN: 978-91-7447-347-6 (print)OAI: oai:DiVA.org:su-60540DiVA: diva2:435803
Public defence
2011-09-22, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
Opponent
Supervisors
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
List of papers
1. Immunogenicity and antigenic properties of Pf332-C231, a fragment of a non-repeat region of the Plasmodium falciparum antigen Pf332
Open this publication in new window or tab >>Immunogenicity and antigenic properties of Pf332-C231, a fragment of a non-repeat region of the Plasmodium falciparum antigen Pf332
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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.

Keyword
Plasmodium falciparum, Pf332-C231, Growth inhibition
National Category
Immunology
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-32902 (URN)10.1016/j.vaccine.2009.09.110 (DOI)000274869200012 ()19822232 (PubMedID)
Available from: 2009-12-17 Created: 2009-12-17 Last updated: 2017-12-12Bibliographically approved
2. Pf332-C231- reactive antibodies affect growth and development of intraerythrocytic Plasmodium falciparum parasites
Open this publication in new window or tab >>Pf332-C231- reactive antibodies affect growth and development of intraerythrocytic Plasmodium falciparum parasites
(English)Article in journal (Refereed) Submitted
Keyword
Malaria, Pf332-C231, antibodies, growth inhibition
National Category
Infectious Medicine Immunology
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-60515 (URN)
Available from: 2011-08-19 Created: 2011-08-18 Last updated: 2011-08-22Bibliographically approved
3. Antibody responses to a C-terminal fragment of the Plasmodium falciparum blood-stage antigen Pf332 in Senegalese individuals naturally primed to the parasite
Open this publication in new window or tab >>Antibody responses to a C-terminal fragment of the Plasmodium falciparum blood-stage antigen Pf332 in Senegalese individuals naturally primed to the parasite
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2008 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 152, no 1, 64-71 p.Article in journal (Refereed) Published
Abstract [en]

Previous studies have shown that antibodies from humans exposed continuously to malaria recognize the Plasmodium falciparum asexual blood-stage antigen Pf332. Here we analysed the antibody responses to a C-terminal fragment of Pf332, designated C231, in individuals from Senegal, by measuring the serum levels of immunoglobulin M (IgM), IgG class and subclass and IgE antibodies. IgG antibody reactivity with crude P. falciparum antigen was detected in all the donors, while many of the children lacked or had low levels of such antibodies against C231. The antibody levels increased significantly with age for both crude P. falciparum antigen and C231, and in the older age groups most of the donors displayed antibodies to C231. This was also true for IgM, IgE and IgG subclass reactivity against C231. Moreover, the ratio of IgG1/IgG2 was considerably lower for C231 than for crude P. falciparum antigen, and in age groups 10–14 and 15–19 years the levels of IgG2 against C231 even exceeded that of IgG1. The IgG2/IgG3 ratios suggest that C231 gives similar levels of IgG2 and IgG3, except for children aged 4–9 years, where IgG3 was higher. Raw IgM, IgG class and subclass and IgE antibody levels to C231 tended to be higher in those who did not experience a malaria attack, but following linear multivariate analysis the trends were not significant.

Keyword
antibody responses, antigen/epitopes, immunoglobulins, Plasmodium spp
National Category
Immunology
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-15992 (URN)10.1111/j.1365-2249.2008.03607.x (DOI)000253757700010 ()18279441 (PubMedID)
Available from: 2008-12-12 Created: 2008-12-12 Last updated: 2017-12-13Bibliographically approved
4. Pattern of antibodies to the Duffy binding-like domain of Plasmodium falciparum antigen Pf332 in Senegalese individuals
Open this publication in new window or tab >>Pattern of antibodies to the Duffy binding-like domain of Plasmodium falciparum antigen Pf332 in Senegalese individuals
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(English)Manuscript (preprint) (Other academic)
Keyword
Pf332-DBL, antibody response, IgG3 subclass, Immunity, malaria attack
National Category
Infectious Medicine Immunology
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-60517 (URN)
Available from: 2011-08-18 Created: 2011-08-18 Last updated: 2011-08-22Bibliographically approved

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