Cross-sectional seroepidemiological studies of populations naturally exposed to Plasmodium falciparum suggest an association between protection from
malaria and circulating
antibodies to the carboxyl terminus of
merozoite surface protein 1 (
MSP1). Questions remain regarding the significance of cell-mediated immunity to
MSP1 in conferring protection and inducing immunologic memory.
Vaccine constructs have been based on the 42-kDa recombinant
MSP1 protein (
MSP1(42)), which includes the 19-kDa (
MSP1(19)) and 33-kDa (
MSP1(33)) fragments containing the major B- and
T-cell epitopes, respectively. To evaluate T-cell responses to the
MSP1(33) fragment, two libraries of overlapping 18-mer
peptides from the 3D7 and FVO
MSP1(33) regions were used to screen a cohort of asymptomatic Kenyan adults.
Gamma interferon (IFN-γ) measured by
enzyme-linked immunospot assay (ELISPOT) at multiple time points assessed the magnitude and stability of these responses. The percentage of individuals with IFN-γ responses to single
MSP1(33)
peptides ranged from nil to 24%, were clustered among a subset of
peptides, and were not consistently recalled over time. In comparison to
peptide responses, IFN-γ ELISPOT responses to recombinant
MSP1(42) were more prevalent, more frequently elicited by the 3D7 as opposed to the FVO allele, and more stable over time. The prevailing
MSP1(33) genotype
infection was 3D7, with few
mixed infections and no sole FVO
infections. This study demonstrates that immunity against
MSP1(33) after cumulative natural
infections consists of low-magnitude and difficult-to-detect IFN-γ responses. Although immunity against
MSP1 alone will not confer protection against
malaria, demonstrating a relative and sustained increase in T-cell immunity to
MSP1 after vaccination would be a reasonable measurement of
vaccine responsiveness.