Stable Plasmodium falciparum merozoite surface protein-1 allelic diversity despite decreasing parasitemia in children with multiple malaria infections

Individuals experiencing recurrent malaria infections encounter a variety of alleles with each new infection. This ongoing allelic diversity influences the development of naturally acquired immunity and it can inform vaccine efficacy. To investigate the diversity and infection variability, Plasmodium falciparum merozoite surface protein 1 (Pfmsp1), a crucial protein for parasite invasion and immune response, was assessed in parasites isolated from children with repeated malaria episodes. A total of eleven microhaplotypes were observed across all malaria episodes. There were 4 prevalent microhaplotypes, E-KSNG-L, Q-KSNG-L, Q-KSNG-F, and Q-KNNG-L, in the population. Conversely, microhaplotypes such as E-KSSR-L, E-KNNG-L, E-KSSG-L, E-TSSR-L (3D7), Q-TSSR-L, E-TSSG-L, and E-KSNG-F were rare and maintained at low frequencies. High allelic replacements were observed, however some individuals experienced consecutive re-infections with the same microhaplotype. Notably, Pfmsp119 allelic diversity as measured by haplotype diversity was stable, while nucleotide diversity decreased over time with decreasing parasitemia. Parasite Pfmsp119 allelic diversity remained stable over the multiple malaria episodes, despite declining parasitaemia levels and ongoing immune development. In addition, our findings reveal dynamic Pfmsp119 allelic replacements across parasite infection episodes, with initial immune responses to prevalent variants potentially waning over time, allowing for re-infections. Overall, our findings emphasize that protective immunity to malaria involves complex immune responses targeting multiple alleles that wane over time and thus the development of sterilizing immunity is a challenge.