Research

Cellular responses to modified Plasmodium falciparum MSP1₁₉ antigens in individuals previously exposed to natural malaria infection

Christian MF Okafor^1,5 , Chiaka I Anumudu¹ , Yusuf O Omosun^1,6 , Chairat Uthaipibull^3,7 , Idowu Ayede² , Henrietta O Awobode¹ , Alex B Odaibo¹ , Jean Langhorne³ , Anthony A Holder³ , Roseangela I Nwuba¹ and Marita Troye-Blomberg⁴

¹  Cellular Parasitology Programme, Department of Zoology University of Ibadan, Ibadan, Nigeria

²  Oni Memorial Children's Hospital, Ring Road, Ibadan, Nigeria

³  Division of Parasitology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK

⁴  Department of Immunology, Wenner-Gren Institute, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden

⁵  College of Art and Sciences, Northwest University, 5520, 108th Ave. NE, Kirkland WA 98033, USA

⁶  Department of Biotechnology, Bells University of Technology, Sango-Otta, Nigeria

⁷  Protein-Ligand Engineering and Molecular Biology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC), Thailand Science Park, Pathumthani, Thailand

author email corresponding author email

Malaria Journal 2009, 8:263doi:10.1186/1475-2875-8-263

Published:	23 November 2009

Abstract

Background

MSP1 processing-inhibitory antibodies bind to epitopes on the 19 kDa C-terminal region of the Plasmodium falciparum merozoite surface protein 1 (MSP1₁₉), inhibiting erythrocyte invasion. Blocking antibodies also bind to this antigen but prevent inhibitory antibodies binding, allowing invasion to proceed. Recombinant MSP1₁₉ 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 MSP1₁₉ would affect critical T-cell responses to epitopes in this antigen.

Methods

The cellular responses to wild-type MSP1₁₉ and a panel of modified MSP1₁₉ antigens were measured using an in-vitro assay for two groups of individuals: the first were malaria-naïve 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 MSP1₁₉. 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 MSP1₁₉ 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.