@article{fdi:010049405,
  title = {{C}linical protection from {F}alciparum {M}alaria correlates with neutrophil respiratory bursts induced by merozoites opsonized with human serum antibodies},
  author = {{J}oos, {C}. and {M}arrama, {L}. and {P}olson, {H}. {E}. {J}. and {C}orre, {S}. and {D}iatta, {A}. {M}. and {D}iouf, {B}. and {T}rape, {J}ean-{F}ran{\c{c}}ois and {T}all, {A}. and {L}ongacre, {S}. and {P}erraut, {R}.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground: {E}ffective vaccines to combat malaria are urgently needed, but have proved elusive in the absence of validated correlates of natural immunity. {R}epeated blood stage infections induce antibodies considered to be the main arbiters of protection from pathology, but their essential functions have remained speculative. {M}ethodology/{P}rincipal {F}indings: {T}his study evaluated antibody dependent respiratory burst ({ADRB}) activity in polymorphonuclear neutrophils ({PMN}) induced by {P}lasmodium falciparum merozoites and antibodies in the sera of two different {A}frican endemic populations, and investigated its association with naturally acquired clinical protection. {R}espiratory bursts by freshly isolated {PMN} were quantified by chemiluminescence readout in the presence of isoluminol, which preferentially detects extra-cellular reactive oxygen species ({ROS}). {U}sing a standardized, high throughput protocol, 230 sera were analyzed from individuals of all age groups living in meso-({N}diop) or holo-endemic ({D}ielmo) {S}enegalese villages, and enrolled in a cross-sectional prospective study with intensive follow-up. {S}tatistical significance was determined using non-parametric tests and {P}oisson regression models. {T}he most important finding was that {PMN} {ADRB} activity was correlated with acquired clinical protection from malaria in both high and low transmission areas ({P} = 0.006 and 0.036 respectively). {S}trikingly, individuals in {D}ielmo with dichotomized high {ADRB} indexes were seventeen fold less susceptible to malaria attacks ({P} = 0.006). {C}omplementary results showed that {ADRB} activity was (i) dependent on intact merozoites and {I}g{G} opsonins, but not parasitized erythrocytes, or complement, (ii) correlated with merozoite specific cytophilic {I}g{G}1 and {I}g{G}3 antibody titers ({P} < 0.001 for both), and (iii) stronger in antisera from a holo-endemic compared to a meso-endemic site ({P} = 0.002), and reduced in asymptomatic carriers ({P} < 0.001). {C}onclusions/{S}ignificance: {T}his work presents the first clearly demonstrated functional antibody immune correlate of clinical protection from {P}lasmodium falciparum malaria, and begs the question regarding the importance of {ADRB} by {PMN} for immune protection against malaria in vivo.},
  keywords = {},
  booktitle = {},
  journal = {{P}los {O}ne},
  volume = {5},
  numero = {3},
  pages = {e9871},
  ISSN = {1932-6203},
  year = {2010},
  DOI = {10.1371/journal.pone.0009871},
  URL = {https://www.documentation.ird.fr/hor/fdi:010049405},
}