Individuals acquire immunity to clinical malaria after repeated Plasmodium falciparum infections. Immunity to disease is thought to reflect the acquisition of a repertoire of responses to multiple alleles in diverse parasite antigens. In previous studies, we identified polymorphic sites within individual antigens that are associated with parasite immune evasion by examining antigen allele dynamics in individuals followed longitudinally. Here we expand this approach by analyzing genome-wide polymorphisms using whole genome sequence data from 140 parasite isolates representing malaria cases from a longitudinal study in Malawi and identify 25 genes that encode possible targets of naturally acquired immunity that should be validated immunologically and further characterized for their potential as vaccine candidates. Author summary Each year, there are hundreds of millions of cases of malaria resulting in several hundred thousand deaths. In malaria-endemic areas with high transmission, individuals experience malaria illness multiple times during their lifetimes, and after many infections, develop immunity that prevents symptoms. The proteins targeted by acquired immunity are not fully known. Understanding which proteins are targets of protective immune responses may aid in development of a malaria vaccine. Here, we used whole-genome sequence data from malaria parasites collected from symptomatic individuals in Malawi to identify targets of malaria immunity based on the frequency of different sequence variants observed in people with different levels of immunity and in individuals over time. Using the combined results of these approaches, we identified genes encoding 25 proteins that may be targets of clinical immunity to malaria that will be further investigated in future studies for their potential as vaccine candidate antigens.
【초록키워드】 Vaccine, Immunity, variant, polymorphism, Transmission, Symptoms, malaria parasites, Antigen, malaria, Protein, immune evasion, infections, longitudinal study, immune responses, response, understanding, vaccine candidate, antigens, target, targets, acquired immunity, disease, Frequency, naturally acquired immunity, deaths, Plasmodium falciparum, multiple alleles, Previous studies, approaches, individual, protective immune response, sequence, symptomatic individuals, allele, vaccine candidates, repertoire, acquisition, whole genome sequence, Whole-genome sequence, isolate, repeated, approach, Prevent, thought, resulting, identify, collected, develop, investigated, characterized, representing, expand, genes encoding, immunologically, malaria parasite, multiple allele, polymorphic site, symptomatic individual, 【제목키워드】 Immunity, target, Analysis, isolate, identify,