Geographical patterns of allelic diversity in the<i>Plasmodium falciparum</i>malaria-vaccine candidate, merozoite surface protein-2

Hoffmann, Érika Hellena Esther; Silveira, Leonardo Evangelista da; Tonhosolo, Renata; Pereira, Fabrício José Tarelho; Ribeiro, Weber Luidi; Tonon, Ângela Pedroso; Kawamoto, Fumihiko; Ferreira, Marcelo U.

doi:10.1080/00034983.2001.11813622

Cited by 28 publications

(30 citation statements)

References 43 publications

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“…In the largest population sample from a single geographical location to date, 214 unique haplotypes of the ectodomain were found in 506 samples from Mali (51). These differences in haplotype diversity are likely to reflect differences in malaria transmission, as has been observed at other polymorphic loci where higher transmission is generally associated with increased diversity (4,24,49). This is generally due to the combined effects of a higher effective population size and a higher effective recombination rate (i.e., outcrossing) as well as a possible additional effect of stronger balancing selection in the case of loci encoding antigens such as AMA1.…”

Section: Discussionmentioning

confidence: 93%

Allelic Diversity and Naturally Acquired Allele-Specific Antibody Responses to Plasmodium falciparum Apical Membrane Antigen 1 in Kenya

et al. 2010

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Although Plasmodium falciparum apical membrane antigen 1 (AMA1) is a leading malaria vaccine candidate, extensive allelic diversity may compromise its vaccine potential. We have previously shown that naturally acquired antibodies to AMA1 were associated with protection from clinical malaria in this Kenyan population. To assess the impact of allelic diversity on naturally acquired immunity, we first sequenced the ectodomainencoding region of P. falciparum ama1 from subjects with asymptomatic, mild, and severe malaria and measured allele frequency distributions. We then measured antibodies to three allelic AMA1 proteins (AMA1_3D7, AMA1_FVO, and AMA1_HB3) and used competition enzyme-linked immunosorbent assays (ELISAs) to analyze allele-specific antibodies. Seventy-eight unique haplotypes were identified from 129 alleles sampled. No clustering of allelic haplotypes with disease severity or year of sampling was observed. Differences in nucleotide frequencies in clinical (severe plus mild malaria) versus asymptomatic infections were observed at 16 polymorphic positions. Allele frequency distributions were indicative of balancing selection, with the strongest signature being identified in domain III (Tajima's D ‫؍‬ 2.51; P < 0.05). Antibody reactivities to each of the three allelic AMA1 proteins were highly correlated (P < 0.001 for all pairwise comparisons). Although antibodies to conserved epitopes were abundant, 48% of selected children with anti-AMA1 IgG (n ‫؍‬ 106) had detectable reactivity to allele-specific epitopes as determined by a competition ELISA. Antibodies to both conserved and allele-specific epitopes in AMA1 may contribute to clinical protection.

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Section: Discussionmentioning

confidence: 93%

Allelic Diversity and Naturally Acquired Allele-Specific Antibody Responses to Plasmodium falciparum Apical Membrane Antigen 1 in Kenya

et al. 2010

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“…This may reflect the higher transmission intensity in Africa, associated previously with increased diversity (2,3,27), but may also reflect the longer evolutionary time of P. falciparum in Africa (9) and the relative isolation of Papua New Guinea from other major malarious areas. More interesting results came from interpopulation diversity comparisons, which revealed that the ama1 domain I haplotype repertoires in Wosera and Nigeria overlap only slightly.…”

Section: Discussionmentioning

confidence: 99%

Geographical Structure of Diversity and Differences between Symptomatic and Asymptomatic Infections for Plasmodium falciparum Vaccine Candidate AMA1

et al. 2003

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Plasmodium falciparum apical membrane antigen 1 (AMA1) is a prime malaria vaccine candidate. Antigenic diversity within parasite populations is one of the main factors potentially limiting the efficacy of any asexual-stage vaccine, including one based on AMA1. The DNA coding for the most variable region of this antigen, domain I, was sequenced in 168 samples from the Wosera region of Papua New Guinea, including samples from symptomatic and asymptomatic infections. Neutrality tests applied to these sequences provided strong evidence of selective pressure operating on the sequence of ama1 domain I, consistent with AMA1 being a target of protective immunity. Similarly, a peculiar pattern of geographical diversity and the particular substitutions found were suggestive of strong constraints acting on the evolution of AMA1 at the population level, probably as a result of immune pressure. In addition, a strong imbalance between symptomatic and asymptomatic infections was detected in the frequency of particular residues at certain polymorphic positions, pointing to AMA1 as being one of the determinants of the morbidity associated with a particular strain. The information yielded by this study has implications for the design and assessment of AMA1-based vaccines and provides additional data supporting the importance of AMA1 as a malaria vaccine candidate.

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“…Recombination events comprise both exchanges of blocks of homologous sequences during meiosis and rearrangements in repeat arrays during both mitosis and meiosis. The extensive variation in CSP, MSP-2, and many other antigens results primarily from insertions and deletions of repeat motifs (12,33,54,90). In contrast, both exchanges of nonrepetitive sequences and rearrangements within repeat arrays seem to generate new msp-1 alleles in natural populations of P. falciparum (35) and P. vivax (87).…”

Section: Repetitive Antigens and Allelic Polymorphismmentioning

confidence: 99%

“…2-to 10-mer GSA-rich motifs, which are typical of the allelic family IC1 (54). These repeats are targeted by parasite-inhibitory antibodies (31,34,88) and contain T-cell epitopes (98).…”

Section: Repetitive Antigens and Allelic Polymorphismmentioning

confidence: 99%

Antigenic Diversity and Immune Evasion by Malaria Parasites

Ferreira

Nunes

Wunderlich

2004

Clin Vaccine Immunol

106

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Geographical patterns of allelic diversity in thePlasmodium falciparummalaria-vaccine candidate, merozoite surface protein-2

Cited by 28 publications

References 43 publications

Allelic Diversity and Naturally Acquired Allele-Specific Antibody Responses to Plasmodium falciparum Apical Membrane Antigen 1 in Kenya

Allelic Diversity and Naturally Acquired Allele-Specific Antibody Responses to Plasmodium falciparum Apical Membrane Antigen 1 in Kenya

Geographical Structure of Diversity and Differences between Symptomatic and Asymptomatic Infections for Plasmodium falciparum Vaccine Candidate AMA1

Antigenic Diversity and Immune Evasion by Malaria Parasites

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