@article{fdi:010070257,
  title = {{C}linical development of a {VAR}2{CSA}-based placental malaria vaccine {PAMVAC} : quantifying vaccine antigen-specific memory {B} & {T} cell activity in {B}eninese primigravidae},
  author = {{G}bedande, {K}. and {F}ievet, {N}adine and {V}iwami, {F}. and {E}zinmegnon, {S}. and {I}ssifou, {S}. and {C}hippaux, {J}ean-{P}hilippe and {D}ossou, {Y}. and {M}outairou, {K}. and {M}assougbodji, {A}. and {N}dam, {N}. and de {J}ongh, {W}. {A}. and {S}ogaard, {T}. {M}. {M}. and {S}alanti, {A}. and {N}ielsen, {M}. {A}. and {E}sen, {M}. and {M}ordmuller, {B}. and {D}eloron, {P}hilippe and {L}uty, {A}drian and {M}ulti-{C}entre {R}esearch {P}aper},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground: {T}he antigen {VAR}2{CSA} plays a pivotal role in the pathophysiology of pregnancy-associated malaria ({PAM}) caused by {P}lasmodium falciparum. {A} {VAR}2{CSA}-based vaccine candidate, {PAMVAC}, is under development by an {EU}-funded multi-country consortium ({P}lac{M}al{V}ac project). {A}s part of {PAMVAC}s clinical development, we quantified naturally acquired vaccine antigen-specific memory {B} and {T} cell responses in {B}eninese primigravidae recruited at the beginning of pregnancy and followed up to delivery and beyond. {M}ethods: {C}linical and parasitological histories were compiled from monthly clinic visits. {O}n 4 occasions (first and fifth month of pregnancy, delivery, 6 months post-delivery) peripheral blood mononuclear cells were isolated for in vitro assays. {PAMVAC}-specific memory {B} cells as well as those specific for a {PAM} unrelated {P}. falciparum antigen ({P}f{EMP}1-{CIDR}1a) and for tetanus toxoid were quantified by {ELIS}pot. {M}emory {T} cell responses were assessed by quantifying cytokines ({IL}-5, {IL}-6, {IL}-10, {IL}-13, {IFN}-gamma, {TNF}-alpha) in supernatants of cells stimulated in vitro either with {PAMVAC}, or mitogen ({PHA}). {R}esults: {B}oth tetanus toxoid- and {PAMVAC}-specific memory {B} cell frequencies increased to reach peak levels in the 5th month and at delivery, respectively and persisted post-delivery. {T}he frequency of {CIDR}1a-specific memory {B} cells was stable during pregnancy, but declined post-delivery. {T}he cumulated prevalence of infection with {P}. falciparum during pregnancy was 61% by microscopy. {I}n women with a history of such infections, a significantly higher frequency of {PAMVAC}-specific memory {B} cells was observed at delivery. {PAMVAC}-specific pro-inflammatory ({IFN}-gamma, {TNF}) responses tended to be higher at delivery in those with a history of infection. {M}itogen-induced {IL}-5/{IL}-13 responses were significantly enhanced in the same women. {C}onclusions: {PAMVAC}-specific memory {B} cells are induced during first pregnancies and are maintained post-delivery. {W}omen with a {T} helper cell profile biased towards production of {T}h2-type cytokines have a greater risk of infection with {P}. falciparum.},
  keywords = {{M}alaria ; {P}regnancy ; {VAR}2{CSA} ; {V}accine ; {C}ytokines ; {T} & {B} cells ; {BENIN}},
  booktitle = {},
  journal = {{V}accine},
  volume = {35},
  numero = {27},
  pages = {3474--3481},
  ISSN = {0264-410{X}},
  year = {2017},
  DOI = {10.1016/j.vaccine.2017.05.027},
  URL = {https://www.documentation.ird.fr/hor/fdi:010070257},
}