Pooled Amplicon Deep Sequencing of Candidate Plasmodium falciparum Transmission-Blocking Vaccine Antigens
Year: 2015
Type: article
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.
Authors: 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
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Tulane University, Karolinska Institutet, Muhimbili University of Health and Allied Sciences, University of Health and Allied Sciences, National Institutes of Health, Gillings School of Public Health, University of North Carolina at Chapel Hill, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
OpenAlex ID: W2238100784