Comparative Assessment of Transmission-Blocking Vaccine Candidates against Plasmodium falciparum
Author(s)
Type
Journal Article
Abstract
Malaria transmission-blocking vaccines (TBVs) target the development of Plasmodium parasites
within the mosquito, with the aim of preventing malaria transmission from one infected individual to
another. Different vaccine platforms, mainly protein-in-adjuvant formulations delivering the leading
candidate antigens, have been developed independently and have reported varied transmissionblocking
activities (TBA). Here, recombinant chimpanzee adenovirus 63, ChAd63, and modified
vaccinia virus Ankara, MVA, expressing AgAPN1, Pfs230-C, Pfs25, and Pfs48/45 were generated.
Antibody responses primed individually against all antigens by ChAd63 immunization in BALB/c
mice were boosted by the administration of MVA expressing the same antigen. These antibodies
exhibited a hierarchy of inhibitory activity against the NF54 laboratory strain of P. falciparum in
Anopheles stephensi mosquitoes using the standard membrane feeding assay (SMFA), with antiPfs230-C
and anti-Pfs25 antibodies giving complete blockade. The observed rank order of inhibition
was replicated against P. falciparum African field isolates in A. gambiae in direct membrane feeding
assays (DMFA). TBA achieved was IgG concentration dependent. This study provides the first headto-head
comparative analysis of leading antigens using two different parasite sources in two different
vector species, and can be used to guide selection of TBVs for future clinical development using the
viral-vectored delivery platform.
within the mosquito, with the aim of preventing malaria transmission from one infected individual to
another. Different vaccine platforms, mainly protein-in-adjuvant formulations delivering the leading
candidate antigens, have been developed independently and have reported varied transmissionblocking
activities (TBA). Here, recombinant chimpanzee adenovirus 63, ChAd63, and modified
vaccinia virus Ankara, MVA, expressing AgAPN1, Pfs230-C, Pfs25, and Pfs48/45 were generated.
Antibody responses primed individually against all antigens by ChAd63 immunization in BALB/c
mice were boosted by the administration of MVA expressing the same antigen. These antibodies
exhibited a hierarchy of inhibitory activity against the NF54 laboratory strain of P. falciparum in
Anopheles stephensi mosquitoes using the standard membrane feeding assay (SMFA), with antiPfs230-C
and anti-Pfs25 antibodies giving complete blockade. The observed rank order of inhibition
was replicated against P. falciparum African field isolates in A. gambiae in direct membrane feeding
assays (DMFA). TBA achieved was IgG concentration dependent. This study provides the first headto-head
comparative analysis of leading antigens using two different parasite sources in two different
vector species, and can be used to guide selection of TBVs for future clinical development using the
viral-vectored delivery platform.
Date Issued
2015-06-11
Date Acceptance
2015-04-23
Citation
Scientific Reports, 2015, 5
ISSN
2045-2322
Publisher
Nature Publishing Group
Journal / Book Title
Scientific Reports
Volume
5
Copyright Statement
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The images or other third party material in this article are included in the article’s Creative
Commons license, unless indicated otherwise in the credit line; if the material is not included under
the Creative Commons license, users will need to obtain permission from the license holder to
reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/
by/4.0/
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Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
SURFACE-ANTIGEN PFS230
MEMBRANE-FEEDING ASSAY
CELL-FREE SYSTEM
MALARIA TRANSMISSION
SEXUAL-STAGE
ADJUVANT VACCINES
VIVAX MALARIA
ANTIBODIES
PROTEIN
RESPONSES
Publication Status
Published
Article Number
11193