@article{fdi:010071904, title = {{A}ssociation of antibodies to {P}lasmodium falciparum merozoite surface protein-4 with protection against clinical malaria}, author = {{P}erraut, {R}. and {V}arela, {M}. {L}. and {J}oos, {C}. and {D}iouf, {B}. and {S}okhna, {C}heikh and {M}bengue, {B}. and {T}all, {A}. and {L}oucoubar, {C}. and {T}oure, {A}. and {M}ercereau-{P}uijalon, {O}.}, editor = {}, language = {{ENG}}, abstract = {{I}dentification of parasite antigens targeted by immune effector mechanisms that confer protection against malaria is important for the design of a multi-component malaria vaccine. {H}ere, the association of antibodies reacting with the {P}lasmodium falciparum merozoite surface protein-4 ({MSP}4) with protection against clinical malaria was investigated in a {S}enegalese community living in an area of moderate, seasonal malaria transmission. {B}lood samples were collected at the end of an 8-month long dry season without any recorded parasite transmission from 206 residents enrolled in a prospective follow-up study. {A}ctive daily clinical monitoring was implemented during the subsequent five months. {E}ntomologic monitoring documented parasite transmission during the first three months of follow-up. {S}erum {I}g{G} levels were determined by {ELISA} against three {MSP}4 baculovirus-encoded recombinant protein constructs, namely the full-length {MSP}4p40, {MSP}4p30 devoid of a highly polymorphic sequence stretch and the conserved {C}-terminal {EGF}-containing {MSP}4p20, as well as against a merozoite crude extract. {C}ommunity seroprevalence against all three constructs was quite high, the lowest being against {MSP}4p30. {S}eroprevalence and antibody levels against the three {MSP}4 constructs were age-dependent. {I}g{G}1 dominated the anti-{MSP}4p20 responses, while both {I}g{G}1 and {I}g{G}3 were observed against {MSP}4p40. {A}nti-{MSP}4 antibodies were associated with the antibody-dependent respiratory burst ({ADRB}) activity in a functional assay of merozoite phagocytosis by polymorphonuclear cells. {I}mportantly, high antibody levels against each of the three {MSP}4 constructs at the end of the dry season were associated with reduced morbidity during the subsequent transmission season in an age-adjusted {P}oisson regression model ({IRR} = 0.65 [0.50-0.83], {P} < 0.001 for responses over the median values). {T}hese data are consistent with a protective role for the naturally acquired anti-{MSP}4 antibodies and support further development of {MSP}4 as a candidate component of malaria vaccine.}, keywords = {{P}. falciparum ; {M}erozoite surface protein 4 ; {V}accine candidate ; {A}ntibody ; {C}linical protection ; {A}ntibody-dependent respiratory burst ; {SENEGAL}}, booktitle = {}, journal = {{V}accine}, volume = {35}, numero = {48}, pages = {6720--6726}, ISSN = {0264-410{X}}, year = {2017}, DOI = {10.1016/j.vaccine.2017.10.012}, URL = {https://www.documentation.ird.fr/hor/fdi:010071904}, }