@article{fdi:010068175, title = {{I}nfections with {P}lasmodium falciparum during pregnancy affect {VAR}2{CSA} {DBL}-5 domain-specific {T} cell cytokine responses}, author = {{G}b{\'e}dand{\'e}, {K}. and {C}ottrell, {G}illes and {V}ianou, {B}. and {I}bitokou, {S}. and {F}ernando, {A}. and {T}roye-{B}lomberg, {M}. and {S}alanti, {A}. and {M}outairou, {K}. and {M}assougbodji, {A}. and {T}uikue {N}dam, {N}icaise and {D}eloron, {P}hilippe and {L}uty, {A}drian and {F}ievet, {N}adine}, editor = {}, language = {{ENG}}, abstract = {{B}ackground: {C}urrent knowledge of human immunological responses to pregnancy-associated malaria-specific {P}lasmodium falciparum protein {VAR}2{CSA} concerns almost exclusively {B} cell-driven antibody-mediated activity. {K}nowledge of {VAR}2{CSA}-specific {T} cell-mediated activity is minimal by comparison, with only a single published report of a study investigating {VAR}2{CSA}-derived peptide-specific {T} cell responses. {T}he study described here represents an attempt to redress this balance. {M}ethods: {W}ithin the framework of a cohort study of 1037 pregnant {B}eninese, sub-groups were selected on the basis of the documented presence/absence of infection with {P}. falciparum and conducted detailed immunological assessments both at inclusion into the study and at delivery. {P}eripheral blood mononuclear cells were isolated, stimulated in vitro, and {VAR}2{CSA} {DBL}-5 domain-specific, {IFN}-gamma-secreting {T}-cell frequencies and cytokine responses were quantified using flow cytometric techniques. {M}ultivariate analyses were used to determine primarily whether the {T} cell-mediated {DBL}5-specific activity measured was associated with infection by {P}. falciparum adjusted for gravidity, anaemia and other cofactors. {R}esults: {I}nfections with {P}. falciparum detected at inclusion were associated with enhanced non-specific {TNF} responses, whilst diminished non-specific and {DBL}-5-specific {IL}-10 responses were associated with infections detected at delivery. {I}nfections during pregnancy led to enhanced non-specific and {DBL}-5-specific {IFN}-gamma responses detectable at delivery but to concomitantly lower {DBL}-5-specific {CD}8+ {IFN}-gamma responses. {P}rospective assessments indicated that non-specific pro-inflammatory responses detectable at inclusion in the study were associated with the occurrence of infections subsequently during pregnancy. {C}onclusions: {T}he findings represent a first step in elucidating the quantity and quality of cellular immunological responses to {VAR}2{CSA}, which will help in the development of the primary vaccine candidate for prevention of pregnancy-associated malaria.}, keywords = {{M}alaria ; {P}regnancy ; {VAR}2{CSA} ; {C}ytokines ; {T} cells ; {BENIN} ; {TANZANIE}}, booktitle = {}, journal = {{M}alaria {J}ournal}, volume = {15}, numero = {}, pages = {art. 485 [11 p.]}, ISSN = {1475-2875}, year = {2016}, DOI = {10.1186/s12936-016-1525-x}, URL = {https://www.documentation.ird.fr/hor/fdi:010068175}, }