@article{fdi:010076082, title = {{N}aturally acquired immunity against immature {P}lasmodium falciparum gametocytes}, author = {{D}antzler, {K}. {W}. and {M}a, {S}. {Y}. and {N}gotho, {P}. and {S}tone, {W}. {J}. {R}. and {T}ao, {D}. {Y}. and {R}ijpma, {S}. and {D}e {N}iz, {M}. and {B}ark, {S}. {K}. {N}. and {J}ore, {M}. {M}. and {R}aaijmakers, {T}. {K}. and {E}arly, {A}. {M}. and {U}baida-{M}ohien, {C}. and {L}emgruber, {L}. and {C}ampo, {J}. {J}. and {T}eng, {A}. {A}. and {L}e, {T}. {Q}. and {W}alker, {C}. {L}. and {H}ermand, {P}. and {D}eterre, {P}. and {D}avies, {D}. {H}. and {F}elgner, {P}. and {M}orlais, {I}sabelle and {W}irth, {D}. {F}. and {N}eafsey, {D}. {E}. and {D}inglasan, {R}. {R}. and {L}aufer, {M}. and {H}uttenhower, {C}. and {S}eydel, {K}. and {T}aylor, {T}. and {B}ousema, {T}. and {M}arti, {M}.}, editor = {}, language = {{ENG}}, abstract = {{T}he recent decline in global malaria burden has stimulated efforts toward {P}lasmodium falciparum elimination. {U}nderstanding the biology of malaria transmission stages may provide opportunities to reduce or prevent onward transmission to mosquitoes. {I}mmature {P}. falciparum transmission stages, termed stages {I} to {IV} gametocytes, sequester in human bone marrow before release into the circulation as mature stage {V} gametocytes. {T}his process likely involves interactions between host receptors and potentially immunogenic adhesins on the infected red blood cell (i{RBC}) surface. {H}ere, we developed a flow cytometry assay to examine immune recognition of live gametocytes of different developmental stages by naturally exposed {M}alawians. {W}e identified strong antibody recognition of the earliest immature gametocyte-i{RBC}s (gi{RBC}s) but not mature stage {V} gi{RBC}s. {C}andidate surface antigens (n = 30), most of them shared between asexual- and gametocyte-i{RBC}s, were identified by mass spectrometry and mouse immunizations, as well as correlations between responses by protein microarray and flow cytometry. {N}aturally acquired responses to a subset of candidate antigens were associated with reduced asexual and gametocyte density, and plasma samples from malaria-infected individuals were able to induce immune clearance of gi{RBC}s in vitro. {I}nfected {RBC} surface expression of select candidate antigens was validated using specific antibodies, and genetic analysis revealed a subset with minimal variation across strains. {O}ur data demonstrate that humoral immune responses to immature gi{RBC}s and shared i{RBC} antigens are naturally acquired after malaria exposure. {T}hese humoral immune responses may have consequences for malaria transmission potential by clearing developing gametocytes, which could be leveraged for malaria intervention.}, keywords = {}, booktitle = {}, journal = {{S}cience {T}ranslational {M}edicine}, volume = {11}, numero = {495}, pages = {art. eaav3963 [14]}, ISSN = {1946-6234}, year = {2019}, DOI = {10.1126/scitranslmed.aav3963}, URL = {https://www.documentation.ird.fr/hor/fdi:010076082}, }