Pooled Amplicon Deep Sequencing of Candidate Plasmodium falciparum Transmission-Blocking Vaccine Antigens

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.

Parobek, Christian M (author)
Brazeau, Nicholas F (author)
Ngasala, Billy (author)
Randrianarivelojosia, Milijaona (author)
Lon, Chanthap (author)
Mwandagalirwa, Kashamuka (author)
Tshefu, Antoinette (author)
Dhar, Ravi (author)
Das, Bidyut K (author)
Hoffman, Irving (author)
Martinson, Francis (author)
Mårtensson, Andreas,1963-Karolinska Institutet,Uppsala universitet,Internationell mödra- och barnhälsovård (IMCH),Internationell barnhälsa och nutrition/Mårtensson(Swepub:uu)andma331 (author)
Saunders, David L (author)
Kumar, Nirbhay (author)
Meshnick, Steven R (author)
Uppsala universitetInternationell mödra- och barnhälsovård (IMCH) (creator_code:org_t)

In:American Journal of Tropical Medicine and Hygiene: American Society of Tropical Medicine and Hygiene94:1, s. 143-1460002-96371476-1645

By the author/editor: Juliano, Jonatha ...; Parobek, Christi ...; Brazeau, Nichola ...; Ngasala, Billy; Randrianariveloj ...; Lon, Chanthap; show more...; Mwandagalirwa, K ...; Tshefu, Antoinet ...; Dhar, Ravi; Das, Bidyut K; Hoffman, Irving; Martinson, Franc ...; Mårtensson, Andr ...; Saunders, David ...; Kumar, Nirbhay; Meshnick, Steven ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Infectious Medic ...

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