TY - JOUR
T1 - Pooled amplicon deep sequencing of candidate plasmodium falciparum transmission-blocking vaccine antigens
AU - Juliano, Jonathan J.
AU - Parobek, Christian M.
AU - Brazeau, Nicholas F.
AU - Ngasala, Billy
AU - Randrianarivelojosia, Milijaona
AU - Lon, Chanthap
AU - Mwandagalirwa, Kashamuka
AU - Tshefu, Antoinette
AU - Dhar, Ravi
AU - Das, Bidyut K.
AU - Hoffman, Irving
AU - Martinson, Francis
AU - Mårtensson, Andreas
AU - Saunders, David L.
AU - Kumar, Nirbhay
AU - Meshnick, Steven R.
N1 - Publisher Copyright:
© 2016 by The American Society of Tropical Medicine and Hygiene.
PY - 2016/1
Y1 - 2016/1
N2 - Polymorphisms within Plasmodium falciparum vaccine candidate antigens have the potential to compromise vaccine efficacy. Understanding the allele frequencies of polymorphisms in critical binding regions of antigens can help in the designing of strain-transcendent vaccines. Here, we adopt a pooled deep-sequencing approach, originally designed to study P. falciparum drug resistance mutations, to study the diversity of two leading transmission-blocking vaccine candidates, Pfs25 and Pfs48/45. We sequenced 329 P. falciparum field isolates from six different geographic regions. Pfs25 showed little diversity, with only one known polymorphism identified in the region associated with binding of transmission-blocking antibodies among our isolates. However, we identified four new mutations among eight non-synonymous mutations within the presumed antibody-binding region of Pfs48/45. Pooled deep sequencing provides a scalable and cost-effective approach for the targeted study of allele frequencies of P. falciparum candidate vaccine antigens.
AB - Polymorphisms within Plasmodium falciparum vaccine candidate antigens have the potential to compromise vaccine efficacy. Understanding the allele frequencies of polymorphisms in critical binding regions of antigens can help in the designing of strain-transcendent vaccines. Here, we adopt a pooled deep-sequencing approach, originally designed to study P. falciparum drug resistance mutations, to study the diversity of two leading transmission-blocking vaccine candidates, Pfs25 and Pfs48/45. We sequenced 329 P. falciparum field isolates from six different geographic regions. Pfs25 showed little diversity, with only one known polymorphism identified in the region associated with binding of transmission-blocking antibodies among our isolates. However, we identified four new mutations among eight non-synonymous mutations within the presumed antibody-binding region of Pfs48/45. Pooled deep sequencing provides a scalable and cost-effective approach for the targeted study of allele frequencies of P. falciparum candidate vaccine antigens.
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U2 - 10.4269/ajtmh.15-0571
DO - 10.4269/ajtmh.15-0571
M3 - Article
C2 - 26503281
AN - SCOPUS:84954290070
SN - 0002-9637
VL - 94
SP - 143
EP - 146
JO - American Journal of Tropical Medicine and Hygiene
JF - American Journal of Tropical Medicine and Hygiene
IS - 1
ER -