@article{fdi:010078034, title = {{F}unctional characterization and comparison of {P}lasmodium falciparum proteins as targets of transmission-blocking antibodies}, author = {{N}ikolaeva, {D}. and {I}llingworth, {J}. {J}. and {M}iura, {K}. and {A}lanine, {D}. {G}. {W}. and {B}rian, {I}. {J}. and {L}i, {Y}. {Y}. and {F}yfe, {A}. {J}. and {D}a, {D}. {F}. and {C}ohuet, {A}nna and {L}ong, {C}. {A}. and {D}raper, {S}. {J}. and {B}iswas, {S}.}, editor = {}, language = {{ENG}}, abstract = {{T}he malaria agent {P}lasmodium falciparum continues to evade control efforts. {D}espite multiple datasets for the {P}lasmodium sexual-stage transcriptome and proteome, there have been no rational screens to identify candidate antigens for transmission-blocking vaccine ({TBV}) development. {W}e demonstrate the use of rational screens and comparative functional assessments in identifying proteins of the {P}. falciparum transmission pathway and establishing a robust pre-clinical {TBV} pipeline. {P}lasmodium falciparum malaria continues to evade control efforts, utilizing highly specialized sexual-stages to transmit infection between the human host and mosquito vector. {I}n a vaccination model, antibodies directed to sexual-stage antigens, when ingested in the mosquito blood meal, can inhibit parasite growth in the midgut and consequently arrest transmission. {D}espite multiple datasets for the {P}lasmodium sexual-stage transcriptome and proteome, there have been no rational screens to identify candidate antigens for transmission-blocking vaccine ({TBV}) development. {T}his study characterizes 12 proteins from across the {P}. falciparum sexual-stages as possible {TBV} targets. {R}ecombinant proteins are heterologously expressed as full-length ectodomains in a mammalian {HEK}293 cell system. {T}he proteins recapitulate native parasite epitopes as assessed by indirect fluorescence assay and a proportion exhibits immunoreactivity when tested against sera from individuals living in malaria-endemic {B}urkina {F}aso and {M}ali. {P}urified {I}g{G} generated to the mosquito-stage parasite antigen enolase demonstrates moderate inhibition of parasite development in the mosquito midgut by the ex vivo standard membrane feeding assay. {T}he findings support the use of rational screens and comparative functional assessments in identifying proteins of the {P}. falciparum transmission pathway and establishing a robust pre-clinical {TBV} pipeline.}, keywords = {{M}alaria ; infectious disease ; immunology ; omics ; protein design ; {SMFA} ; transmission-blocking ; vaccines}, booktitle = {}, journal = {{M}olecular and {C}ellular {P}roteomics}, volume = {19}, numero = {1}, pages = {155--166}, ISSN = {1535-9476}, year = {2020}, DOI = {10.1074/mcp.{RA}117.000036}, URL = {https://www.documentation.ird.fr/hor/fdi:010078034}, }