Exploratory analysis of the effect of helminth infection on the immunogenicity and efficacy of the asexual blood-stage malaria vaccine candidate GMZ2.

<h4>Background</h4>Helminths can modulate the host immune response to Plasmodium falciparum and can therefore affect the risk of clinical malaria. We assessed here the effect of helminth infections on both the immunogenicity and efficacy of the GMZ2 malaria vaccine candidate, a recombina...

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Autores principales:	Odilon Nouatin, Juliana Boex Mengue, Jean Claude Dejon-Agobé, Rolf Fendel, Javier Ibáñez, Ulysse Ateba Ngoa, Jean Ronald Edoa, Bayodé Roméo Adégbité, Yabo Josiane Honkpéhédji, Jeannot Fréjus Zinsou, Aurore Bouyoukou Hounkpatin, Kabirou Moutairou, Andreas Homoet, Meral Esen, Andrea Kreidenweiss, Stephen L Hoffman, Michael Theisen, Adrian J F Luty, Bertrand Lell, Selidji Todagbe Agnandji, Ghyslain Mombo-Ngoma, Michael Ramharter, Peter Kremsner, Benjamin Mordmüller, Ayôla Akim Adegnika
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/bb9e94c7a35042c8863884855ee8d7a3
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spelling	oai:doaj.org-article:bb9e94c7a35042c8863884855ee8d7a32021-11-25T06:31:50ZExploratory analysis of the effect of helminth infection on the immunogenicity and efficacy of the asexual blood-stage malaria vaccine candidate GMZ2.1935-27271935-273510.1371/journal.pntd.0009361https://doaj.org/article/bb9e94c7a35042c8863884855ee8d7a32021-06-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009361https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4>Helminths can modulate the host immune response to Plasmodium falciparum and can therefore affect the risk of clinical malaria. We assessed here the effect of helminth infections on both the immunogenicity and efficacy of the GMZ2 malaria vaccine candidate, a recombinant protein consisting of conserved domains of GLURP and MSP3, two asexual blood-stage antigens of P. falciparum. Controlled human malaria infection (CHMI) was used to assess the efficacy of the vaccine.<h4>Methodology</h4>In a randomized, double-blind Phase I clinical trial, fifty, healthy, lifelong malaria-exposed adult volunteers received three doses of GMZ2 adjuvanted with either Cationic Adjuvant Formulation (CAF) 01 or Alhydrogel, or a control vaccine (Rabies) on days (D) 0, D28 and D56, followed by direct venous inoculation (DVI) of 3,200 P. falciparum sporozoites (PfSPZ Challenge) approximately 13 weeks after last vaccination to assess vaccine efficacy. Participants were followed-up on a daily basis with clinical examinations and thick blood smears to monitor P. falciparum parasitemia for 35 days. Malaria 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 PfSPZ Challenge. Soil-transmitted helminth (STH) infection was assessed by microscopy and by polymerase chain reaction (PCR) on stool, and Schistosoma infection was assessed by microscopy on urine. Participants were considered as infected if positive for any helminth either by PCR and/or microscopy at D0 and/or at D84 (Helm+) and were classified as mono-infection or co-infection. Total vaccine-specific IgG concentrations assessed on D84 were analysed as immunogenicity outcome.<h4>Main findings</h4>The helminth in mono-infection, particularly Schistosoma haematobium and STH were significantly associated with earlier malaria episodes following CHMI, while no association was found in case of coinfection. In further analyses, the anti-GMZ2 IgG concentration on D84 was significantly higher in the S. haematobium-infected and significantly lower in the Strongyloides stercoralis-infected groups, compared to helminth-negative volunteers. Interesting, in the absence of helminth infection, a high anti-GMZ2 IgG concentration on D84 was significantly associated with protection against malaria.<h4>Conclusions</h4>Our results suggest that helminth infection may reduce naturally acquired and vaccine-induced protection against malaria. Vaccine-specific antibody concentrations on D84 may be associated with protection in participants with no helminth infection. These results suggest that helminth infection affect malaria vaccine immunogenicity and efficacy in helminth endemic countries.Odilon NouatinJuliana Boex MengueJean Claude Dejon-AgobéRolf FendelJavier IbáñezUlysse Ateba NgoaJean Ronald EdoaBayodé Roméo AdégbitéYabo Josiane HonkpéhédjiJeannot Fréjus ZinsouAurore Bouyoukou HounkpatinKabirou MoutairouAndreas HomoetMeral EsenAndrea KreidenweissStephen L HoffmanMichael TheisenAdrian J F LutyBertrand LellSelidji Todagbe AgnandjiGhyslain Mombo-NgomaMichael RamharterPeter KremsnerBenjamin MordmüllerAyôla Akim AdegnikaPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 6, p e0009361 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270
spellingShingle	Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Odilon Nouatin Juliana Boex Mengue Jean Claude Dejon-Agobé Rolf Fendel Javier Ibáñez Ulysse Ateba Ngoa Jean Ronald Edoa Bayodé Roméo Adégbité Yabo Josiane Honkpéhédji Jeannot Fréjus Zinsou Aurore Bouyoukou Hounkpatin Kabirou Moutairou Andreas Homoet Meral Esen Andrea Kreidenweiss Stephen L Hoffman Michael Theisen Adrian J F Luty Bertrand Lell Selidji Todagbe Agnandji Ghyslain Mombo-Ngoma Michael Ramharter Peter Kremsner Benjamin Mordmüller Ayôla Akim Adegnika Exploratory analysis of the effect of helminth infection on the immunogenicity and efficacy of the asexual blood-stage malaria vaccine candidate GMZ2.
description	<h4>Background</h4>Helminths can modulate the host immune response to Plasmodium falciparum and can therefore affect the risk of clinical malaria. We assessed here the effect of helminth infections on both the immunogenicity and efficacy of the GMZ2 malaria vaccine candidate, a recombinant protein consisting of conserved domains of GLURP and MSP3, two asexual blood-stage antigens of P. falciparum. Controlled human malaria infection (CHMI) was used to assess the efficacy of the vaccine.<h4>Methodology</h4>In a randomized, double-blind Phase I clinical trial, fifty, healthy, lifelong malaria-exposed adult volunteers received three doses of GMZ2 adjuvanted with either Cationic Adjuvant Formulation (CAF) 01 or Alhydrogel, or a control vaccine (Rabies) on days (D) 0, D28 and D56, followed by direct venous inoculation (DVI) of 3,200 P. falciparum sporozoites (PfSPZ Challenge) approximately 13 weeks after last vaccination to assess vaccine efficacy. Participants were followed-up on a daily basis with clinical examinations and thick blood smears to monitor P. falciparum parasitemia for 35 days. Malaria 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 PfSPZ Challenge. Soil-transmitted helminth (STH) infection was assessed by microscopy and by polymerase chain reaction (PCR) on stool, and Schistosoma infection was assessed by microscopy on urine. Participants were considered as infected if positive for any helminth either by PCR and/or microscopy at D0 and/or at D84 (Helm+) and were classified as mono-infection or co-infection. Total vaccine-specific IgG concentrations assessed on D84 were analysed as immunogenicity outcome.<h4>Main findings</h4>The helminth in mono-infection, particularly Schistosoma haematobium and STH were significantly associated with earlier malaria episodes following CHMI, while no association was found in case of coinfection. In further analyses, the anti-GMZ2 IgG concentration on D84 was significantly higher in the S. haematobium-infected and significantly lower in the Strongyloides stercoralis-infected groups, compared to helminth-negative volunteers. Interesting, in the absence of helminth infection, a high anti-GMZ2 IgG concentration on D84 was significantly associated with protection against malaria.<h4>Conclusions</h4>Our results suggest that helminth infection may reduce naturally acquired and vaccine-induced protection against malaria. Vaccine-specific antibody concentrations on D84 may be associated with protection in participants with no helminth infection. These results suggest that helminth infection affect malaria vaccine immunogenicity and efficacy in helminth endemic countries.
format	article
author	Odilon Nouatin Juliana Boex Mengue Jean Claude Dejon-Agobé Rolf Fendel Javier Ibáñez Ulysse Ateba Ngoa Jean Ronald Edoa Bayodé Roméo Adégbité Yabo Josiane Honkpéhédji Jeannot Fréjus Zinsou Aurore Bouyoukou Hounkpatin Kabirou Moutairou Andreas Homoet Meral Esen Andrea Kreidenweiss Stephen L Hoffman Michael Theisen Adrian J F Luty Bertrand Lell Selidji Todagbe Agnandji Ghyslain Mombo-Ngoma Michael Ramharter Peter Kremsner Benjamin Mordmüller Ayôla Akim Adegnika
author_facet	Odilon Nouatin Juliana Boex Mengue Jean Claude Dejon-Agobé Rolf Fendel Javier Ibáñez Ulysse Ateba Ngoa Jean Ronald Edoa Bayodé Roméo Adégbité Yabo Josiane Honkpéhédji Jeannot Fréjus Zinsou Aurore Bouyoukou Hounkpatin Kabirou Moutairou Andreas Homoet Meral Esen Andrea Kreidenweiss Stephen L Hoffman Michael Theisen Adrian J F Luty Bertrand Lell Selidji Todagbe Agnandji Ghyslain Mombo-Ngoma Michael Ramharter Peter Kremsner Benjamin Mordmüller Ayôla Akim Adegnika
author_sort	Odilon Nouatin
title	Exploratory analysis of the effect of helminth infection on the immunogenicity and efficacy of the asexual blood-stage malaria vaccine candidate GMZ2.
title_short	Exploratory analysis of the effect of helminth infection on the immunogenicity and efficacy of the asexual blood-stage malaria vaccine candidate GMZ2.
title_full	Exploratory analysis of the effect of helminth infection on the immunogenicity and efficacy of the asexual blood-stage malaria vaccine candidate GMZ2.
title_fullStr	Exploratory analysis of the effect of helminth infection on the immunogenicity and efficacy of the asexual blood-stage malaria vaccine candidate GMZ2.
title_full_unstemmed	Exploratory analysis of the effect of helminth infection on the immunogenicity and efficacy of the asexual blood-stage malaria vaccine candidate GMZ2.
title_sort	exploratory analysis of the effect of helminth infection on the immunogenicity and efficacy of the asexual blood-stage malaria vaccine candidate gmz2.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/bb9e94c7a35042c8863884855ee8d7a3
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Exploratory analysis of the effect of helminth infection on the immunogenicity and efficacy of the asexual blood-stage malaria vaccine candidate GMZ2.

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