TY - JOUR
T1 - Use of massively parallel pyrosequencing to evaluate the diversity of and selection on plasmodium falciparum csp T-cell epitopes in Lilongwe, Malawi
AU - Bailey, Jeffrey A.
AU - Mvalo, Tisungane
AU - Aragam, Nagesh
AU - Weiser, Matthew
AU - Congdon, Seth
AU - Kamwendo, Debbie
AU - Martinson, Francis
AU - Hoffman, Irving
AU - Meshnick, Steven R.
AU - Juliano, Jonathan J.
N1 - Funding Information:
Financial support. This work was supported by the National Institutes of Health (grants 1RO1AI089819, KL2RR025746, and UL1RR025747).
PY - 2012/8/15
Y1 - 2012/8/15
N2 - The development of an effective malaria vaccine has been hampered by the genetic diversity of commonly used target antigens. This diversity has led to concerns about allele-specific immunity limiting the effectiveness of vaccines. Despite extensive genetic diversity of circumsporozoite protein (CS), the most successful malaria vaccine is RTS/S, a monovalent CS vaccine. By use of massively parallel pyrosequencing, we evaluated the diversity of CS haplotypes across the T-cell epitopes in parasites from Lilongwe, Malawi. We identified 57 unique parasite haplotypes from 100 participants. By use of ecological and molecular indexes of diversity, we saw no difference in the diversity of CS haplotypes between adults and children. We saw evidence of weak variant-specific selection within this region of CS, suggesting naturally acquired immunity does induce variant-specific selection on CS. Therefore, the impact of CS vaccines on variant frequencies with widespread implementation of vaccination requires further study.
AB - The development of an effective malaria vaccine has been hampered by the genetic diversity of commonly used target antigens. This diversity has led to concerns about allele-specific immunity limiting the effectiveness of vaccines. Despite extensive genetic diversity of circumsporozoite protein (CS), the most successful malaria vaccine is RTS/S, a monovalent CS vaccine. By use of massively parallel pyrosequencing, we evaluated the diversity of CS haplotypes across the T-cell epitopes in parasites from Lilongwe, Malawi. We identified 57 unique parasite haplotypes from 100 participants. By use of ecological and molecular indexes of diversity, we saw no difference in the diversity of CS haplotypes between adults and children. We saw evidence of weak variant-specific selection within this region of CS, suggesting naturally acquired immunity does induce variant-specific selection on CS. Therefore, the impact of CS vaccines on variant frequencies with widespread implementation of vaccination requires further study.
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U2 - 10.1093/infdis/jis329
DO - 10.1093/infdis/jis329
M3 - Article
C2 - 22551816
AN - SCOPUS:84866943868
SN - 0022-1899
VL - 206
SP - 580
EP - 587
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 4
ER -