@article{fdi:010081535,
  title = {{E}xploratory analysis of the effect of helminth infection on the immunogenicity and efficacy of the asexual blood-stage malaria vaccine candidate {GMZ}2},
  author = {{N}ouatin, {O}. and {M}engue, {J}. {B}. and {D}ejon-{A}gobe, {J}. {C}. and {F}endel, {R}. and {I}banez, {J}. and {N}goa, {U}. {A}. and {E}doa, {J}. {R}. and {A}degbite, {B}. {R}. and {H}onkpehedji, {Y}. {J}. and {Z}insou, {J}. {F}. and {H}ounkpatin, {A}. {B}. and {M}outairou, {K}. and {H}omoet, {A}. and {E}sen, {M}. and {K}reidenweiss, {A}. and {H}offman, {S}. {L}. and {T}heisen, {M}. and {L}uty, {A}drian and {L}ell, {B}. and {A}gnandji, {S}. {T}. and {M}ombo-{N}goma, {G}. and {R}amharter, {M}. and {K}remsner, {P}. and {M}ordmuller, {B}. and {A}degnika, {A}. {A}.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground {H}elminths can modulate the host immune response to {P}lasmodium falciparum and can therefore affect the risk of clinical malaria. {W}e assessed here the effect of helminth infections on both the immunogenicity and efficacy of the {GMZ}2 malaria vaccine candidate, a recombinant protein consisting of conserved domains of {GLURP} and {MSP}3, two asexual blood-stage antigens of {P}. falciparum. {C}ontrolled human malaria infection ({CHMI}) was used to assess the efficacy of the vaccine. {M}ethodology {I}n a randomized, double-blind {P}hase {I} clinical trial, fifty, healthy, lifelong malaria-exposed adult volunteers received three doses of {GMZ}2 adjuvanted with either {C}ationic {A}djuvant {F}ormulation ({CAF}) 01 or {A}lhydrogel, or a control vaccine ({R}abies) on days ({D}) 0, {D}28 and {D}56, followed by direct venous inoculation ({DVI}) of 3,200 {P}. falciparum sporozoites ({P}f{SPZ} {C}hallenge) approximately 13 weeks after last vaccination to assess vaccine efficacy. {P}articipants were followed-up on a daily basis with clinical examinations and thick blood smears to monitor {P}. falciparum parasitemia for 35 days. {M}alaria was defined as the presence of {P}. falciparum parasites in the blood associated with at least one symptom that can be associated to malaria over 35 days following {DVI} of {P}f{SPZ} {C}hallenge. {S}oil-transmitted helminth ({STH}) infection was assessed by microscopy and by polymerase chain reaction ({PCR}) on stool, and {S}chistosoma infection was assessed by microscopy on urine. {P}articipants were considered as infected if positive for any helminth either by {PCR} and/or microscopy at {D}0 and/or at {D}84 ({H}elm+) and were classified as mono-infection or co-infection. {T}otal vaccine-specific {I}g{G} concentrations assessed on {D}84 were analysed as immunogenicity outcome. {M}ain findings {T}he helminth in mono-infection, particularly {S}chistosoma haematobium and {STH} were significantly associated with earlier malaria episodes following {CHMI}, while no association was found in case of coinfection. {I}n further analyses, the anti-{GMZ}2 {I}g{G} concentration on {D}84 was significantly higher in the {S}. haematobium-infected and significantly lower in the {S}trongyloides stercoralis-infected groups, compared to helminth-negative volunteers. {I}nteresting, in the absence of helminth infection, a high anti-{GMZ}2 {I}g{G} concentration on {D}84 was significantly associated with protection against malaria. {C}onclusions {O}ur results suggest that helminth infection may reduce naturally acquired and vaccine-induced protection against malaria. {V}accine-specific antibody concentrations on {D}84 may be associated with protection in participants with no helminth infection. {T}hese results suggest that helminth infection affect malaria vaccine immunogenicity and efficacy in helminth endemic countries. {A}uthor summary {H}elminths, mainly because of their immune regulatory effects, are able to impact the response induced by vaccines. {I}n the context of clinical trial designs that measure accrual of natural infections during follow up or outcome of controlled human malaria infection ({CHMI}), their effect on vaccine efficacy can be measured. {I}ndeed, most of such clinical trials on malaria vaccine candidates conducted in {A}frica, especially where the prevalence of helminths is high, have shown a certain limit in their efficacy and immunogenicity, as compared to results observed in {E}uropean and {U}.{S} volunteers. {T}he present analysis assessed the effect of helminths on {GMZ}2, a malaria vaccine candidate. {W}e found a high level of anti-{GMZ}2 antibodies among volunteers not infected with helminths and protected against {CHMI}, indicating efficacy of the candidate vaccine in this population. {W}e found a species-dependent effect of helminths on the level of post-immunization {GMZ}2-specific {I}g{G} concentration, and an association of helminths with an early onset of malaria in {CHMI}. {O}ur findings reveal that helminths are associated with immunogenicity and may decrease the protective effect of antibodies induced by vaccination. {H}elminth infection status shall be determined when measuring the immunogenicity and efficacy of malaria vaccine candidates in helminth endemic countries.},
  keywords = {{GABON}},
  booktitle = {},
  journal = {{PL}o{S} {N}eglected {T}ropical {D}iseases},
  volume = {15},
  numero = {6},
  pages = {e0009361 [18 p.]},
  ISSN = {1935-2735},
  year = {2021},
  DOI = {10.1371/journal.pntd.0009361},
  URL = {https://www.documentation.ird.fr/hor/fdi:010081535},
}