Pooled amplicon deep sequencing of candidate plasmodium falciparum transmission-blocking vaccine antigens

Jonathan J. Juliano, Christian M. Parobek, Nicholas F. Brazeau, Billy Ngasala, Milijaona Randrianarivelojosia, Chanthap Lon, Kashamuka Mwandagalirwa, Antoinette Tshefu, Ravi Dhar, Bidyut K. Das, Irving Hoffman, Francis Martinson, Andreas Mårtensson, David L. Saunders, Nirbhay Kumar, Steven R. Meshnick

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)143-146
Number of pages4
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume94
Issue number1
DOIs
StatePublished - Jan 2016

ASJC Scopus subject areas

  • Parasitology
  • Virology
  • Infectious Diseases

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