Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Antibody responses to a C-terminal fragment of the Plasmodium falciparum blood-stage antigen Pf332 in Senegalese individuals naturally primed to the parasite
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.
Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
Show others and affiliations
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.

Place, publisher, year, edition, pages
2008. Vol. 152, no 1, 64-71 p.
Keyword [en]
antibody responses, antigen/epitopes, immunoglobulins, Plasmodium spp
National Category
Immunology
Research subject
Immunology
Identifiers
URN: urn:nbn:se:su:diva-15992DOI: 10.1111/j.1365-2249.2008.03607.xISI: 000253757700010PubMedID: 18279441OAI: oai:DiVA.org:su-15992DiVA: diva2:182512
Available from: 2008-12-12 Created: 2008-12-12 Last updated: 2017-12-13Bibliographically 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)
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
2. 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.
Keyword
malaria, sub-unit vaccines, immunogenicity, antibody response, antigen Pf332
National Category
Immunology
Identifiers
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
Opponent
Supervisors
Available from: 2006-09-21 Created: 2006-09-21 Last updated: 2011-08-22Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Balogun, HalimaBerzins, Klavs
By organisation
Immunology
In the same journal
Clinical and Experimental Immunology
Immunology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 111 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf