Change search
ReferencesLink to record
Permanent link

Direct link
Cellular responses to modified Plasmodium falciparum MSP1(19) antigens in individuals previously exposed to natural malaria infection
Show others and affiliations
2009 (English)In: Malaria Journal, ISSN 1475-2875, Vol. 8, 263- p.Article in journal (Refereed) Published
Abstract [en]

Background: MSP1 processing-inhibitory antibodies bind to epitopes on the 19 kDa C-terminal region of the Plasmodium falciparum merozoite surface protein 1 (MSP1(19)), inhibiting erythrocyte invasion. Blocking antibodies also bind to this antigen but prevent inhibitory antibodies binding, allowing invasion to proceed. Recombinant MSP1(19) had been modified previously to allow inhibitory but not blocking antibodies to continue to bind. Immunization with these modified proteins, therefore, has the potential to induce more effective protective antibodies. However, it was unclear whether the modification of MSP1(19) would affect critical T-cell responses to epitopes in this antigen. Methods: The cellular responses to wild-type MSP1(19) and a panel of modified MSP1(19) antigens were measured using an in-vitro assay for two groups of individuals: the first were malaria-nave and the second had been naturally exposed to Plasmodium falciparum infection. The cellular responses to the modified proteins were examined using cells from malaria-exposed infants and adults. Results: Interestingly, stimulation indices (SI) for responses induced by some of the modified proteins were at least two-fold higher than those elicited by the wild-type MSP1(19). A protein with four amino acid substitutions (Glu27 -> Tyr, Leu31 -> Arg, Tyr34 -> Ser and Glu43 -> Leu) had the highest stimulation index (SI up to 360) and induced large responses in 64% of the samples that had significant cellular responses to the modified proteins. Conclusion: This study suggests that specific MSP1(19) variants that have been engineered to improve their antigenicity for inhibitory antibodies, retain T-cell epitopes and the ability to induce cellular responses. These proteins are candidates for the development of MSP1-based malaria vaccines.

Place, publisher, year, edition, pages
2009. Vol. 8, 263- p.
Keyword [en]
merozoite surface protein-1, carboxyl-terminal fragment, protects aotus monkeys, immune-response, t-cell, clinical immunity, ghanaian children, fine specificity, serum antibodies, disulfide bonds
URN: urn:nbn:se:su:diva-59410DOI: 10.1186/1475-2875-8-263ISI: 000272256300001OAI: diva2:427426
authorCount :11Available from: 2011-06-28 Created: 2011-06-27 Last updated: 2011-06-28Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Troye-Blomberg, Marita
By organisation
The Wenner-Gren Institute
In the same journal
Malaria Journal

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 30 hits
ReferencesLink to record
Permanent link

Direct link