@article{fdi:010078065,
  title = {{E}ffect of immune regulatory pathways after immunization with {GMZ}2 malaria vaccine candidate in healthy lifelong malaria-exposed adults},
  author = {{N}ouatin, {O}. and {N}goa, {U}. {A}. and {I}banez, {J}. and {D}ejon-{A}gobe, {J}. {C}. and {M}ordmuller, {B}. and {E}doa, {J}. {R}. and {M}ougeni, {F}. and {B}ruckner, {S}. and {H}ounkpatin, {A}. {B}. and {E}sen, {M}. and {T}heisen, {M}. and {M}outairou, {K}. and {H}offman, {S}. {L}. and {I}ssifou, {S}. and {L}uty, {A}drian and {L}oembe, {M}. {M}. and {A}gnandji, {S}. {T}. and {L}ell, {B}. and {K}remsner, {P}. {G}. and {A}degnika, {A}. {A}.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground: {D}espite appreciable immunogenicity in malaria-naive populations, many candidate malaria vaccines are considerably less immunogenic in malaria-exposed populations. {T}his could reflect induction of immune regulatory mechanisms involving {H}uman {L}eukocyte {A}ntigen {G} ({HLA}-{G}), regulatory {T} ({T}reg), and regulatory {B} ({B}reg) cells. {H}ere, we addressed the question whether there is correlation between these immune regulatory pathways and both plasmablast frequencies and vaccine-specific {I}g{G} concentrations. {M}ethods: {F}ifty {G}abonese adults with lifelong exposure to {P}lasmodium spp were randomized to receive three doses of either 30 mu g or 100 mu g {GMZ}2-{CAF}01, or 100 mu g {GMZ}2-alum, or control vaccine (rabies vaccine) at 4-week intervals. {O}nly plasma and peripheral blood mononuclear cells isolated from blood samples collected before ({D}0) and 28 days after the third vaccination ({D}84) of 35 participants were used to measure s{HLA}-{G} levels and anti-{GMZ}2 {I}g{G} concentrations, and to quantify {T}reg, {B}reg and plasmablast cells. {V}accine efficacy was assessed using controlled human malaria infection ({CHMI}) by direct venous inoculation of {P}lasmodium falciparum sporozoites ({P}f{SPZ} {C}hallenge). {R}esults: {T}he s{HLA}-{G} concentration increased from {D}0 to {D}84 in all {GMZ}2 vaccinated participants and in the control group, whereas {T}reg frequencies increased only in those receiving 30 mu g or 100 mu g {GMZ}2-{CAF}01. {T}he s{HLA}-{G} level on {D}84 was associated with a decrease of the anti-{GMZ}2 {I}g{G} concentration, whereas {T}reg frequencies on {D}0 or on {D}84, and {B}reg frequency on {D}84 were associated with lower plasmablast frequencies. {I}mportantly, having a {D}84:{D}0 ratio of s{HLA}-{G} above the median was associated with an increased risk of {P}. falciparum infection after sporozoites injection. {C}onclusion: {R}egulatory immune responses are induced following immunization. {S}tronger s{HLA}-{G} and {T}reg immune responses may suppress vaccine induced immune responses, and the magnitude of the s{HLA}-{G} response increased the risk of {P}lasmodium falciparum infection after {CHMI}. {T}hese findings could have implications for the design and testing of malaria vaccine candidates in semi-immune individuals.},
  keywords = {s{HLA}-{G} ; {R}egulatory cells ; {GMZ}2 ; {I}mmunogenicity ; {CHMI}},
  booktitle = {},
  journal = {{V}accine},
  volume = {38},
  numero = {27},
  pages = {4263--4272},
  ISSN = {0264-410{X}},
  year = {2020},
  DOI = {10.1016/j.vaccine.2020.04.046},
  URL = {https://www.documentation.ird.fr/hor/fdi:010078065},
}