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


CONCLUSIONS
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.
Okafor
Christian M F
CM
Cellular Parasitology Programme, Department of Zoology University of Ibadan, Ibadan, Nigeria. cmfokafor2001@yahoo.com
Anumudu
Chiaka I
CI
Omosun
Yusuf O
YO
Uthaipibull
Chairat
C
Ayede
Idowu
I
Awobode
Henrietta O
HO
Odaibo
Alex B
AB
Langhorne
Jean
J
Holder
Anthony A
AA
Nwuba
Roseangela I
RI
Troye-Blomberg
Marita
M
D000293:Adolescent; D000328:Adult; D019138:Antibodies, Blocking / Q000276:immunology; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology*; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000276:immunology / Q000378:metabolism*; D010835:Phytohemagglutinins; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
D019138:Antibodies, Blocking; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D010835:Phytohemagglutinins; D015800:Protozoan Proteins; D005982:Glutathione Transferase