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...
Ausführliche Beschreibung
Autor*in: |
Odilon Nouatin [verfasserIn] Juliana Boex Mengue [verfasserIn] Jean Claude Dejon-Agobé [verfasserIn] Rolf Fendel [verfasserIn] Javier Ibáñez [verfasserIn] Ulysse Ateba Ngoa [verfasserIn] Jean Ronald Edoa [verfasserIn] Bayodé Roméo Adégbité [verfasserIn] Yabo Josiane Honkpéhédji [verfasserIn] Jeannot Fréjus Zinsou [verfasserIn] Aurore Bouyoukou Hounkpatin [verfasserIn] Kabirou Moutairou [verfasserIn] Andreas Homoet [verfasserIn] Meral Esen [verfasserIn] Andrea Kreidenweiss [verfasserIn] Stephen L Hoffman [verfasserIn] Michael Theisen [verfasserIn] Adrian J F Luty [verfasserIn] Bertrand Lell [verfasserIn] Selidji Todagbe Agnandji [verfasserIn] Ghyslain Mombo-Ngoma [verfasserIn] Michael Ramharter [verfasserIn] Peter Kremsner [verfasserIn] Benjamin Mordmüller [verfasserIn] Ayôla Akim Adegnika [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2021 |
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Übergeordnetes Werk: |
In: PLoS Neglected Tropical Diseases - Public Library of Science (PLoS), 2008, 15(2021), 6, p e0009361 |
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Übergeordnetes Werk: |
volume:15 ; year:2021 ; number:6, p e0009361 |
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Link aufrufen |
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DOI / URN: |
10.1371/journal.pntd.0009361 |
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Katalog-ID: |
DOAJ072459220 |
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245 | 1 | 0 | |a 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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520 | |a <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. | ||
653 | 0 | |a Arctic medicine. Tropical medicine | |
653 | 0 | |a Public aspects of medicine | |
700 | 0 | |a Juliana Boex Mengue |e verfasserin |4 aut | |
700 | 0 | |a Jean Claude Dejon-Agobé |e verfasserin |4 aut | |
700 | 0 | |a Rolf Fendel |e verfasserin |4 aut | |
700 | 0 | |a Javier Ibáñez |e verfasserin |4 aut | |
700 | 0 | |a Ulysse Ateba Ngoa |e verfasserin |4 aut | |
700 | 0 | |a Jean Ronald Edoa |e verfasserin |4 aut | |
700 | 0 | |a Bayodé Roméo Adégbité |e verfasserin |4 aut | |
700 | 0 | |a Yabo Josiane Honkpéhédji |e verfasserin |4 aut | |
700 | 0 | |a Jeannot Fréjus Zinsou |e verfasserin |4 aut | |
700 | 0 | |a Aurore Bouyoukou Hounkpatin |e verfasserin |4 aut | |
700 | 0 | |a Kabirou Moutairou |e verfasserin |4 aut | |
700 | 0 | |a Andreas Homoet |e verfasserin |4 aut | |
700 | 0 | |a Meral Esen |e verfasserin |4 aut | |
700 | 0 | |a Andrea Kreidenweiss |e verfasserin |4 aut | |
700 | 0 | |a Stephen L Hoffman |e verfasserin |4 aut | |
700 | 0 | |a Michael Theisen |e verfasserin |4 aut | |
700 | 0 | |a Adrian J F Luty |e verfasserin |4 aut | |
700 | 0 | |a Bertrand Lell |e verfasserin |4 aut | |
700 | 0 | |a Selidji Todagbe Agnandji |e verfasserin |4 aut | |
700 | 0 | |a Ghyslain Mombo-Ngoma |e verfasserin |4 aut | |
700 | 0 | |a Michael Ramharter |e verfasserin |4 aut | |
700 | 0 | |a Peter Kremsner |e verfasserin |4 aut | |
700 | 0 | |a Benjamin Mordmüller |e verfasserin |4 aut | |
700 | 0 | |a Ayôla Akim Adegnika |e verfasserin |4 aut | |
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10.1371/journal.pntd.0009361 doi (DE-627)DOAJ072459220 (DE-599)DOAJbb9e94c7a35042c8863884855ee8d7a3 DE-627 ger DE-627 rakwb eng RC955-962 RA1-1270 Odilon Nouatin verfasserin aut Exploratory analysis of the effect of helminth infection on the immunogenicity and efficacy of the asexual blood-stage malaria vaccine candidate GMZ2. 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <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. Arctic medicine. Tropical medicine Public aspects of medicine Juliana Boex Mengue verfasserin aut Jean Claude Dejon-Agobé verfasserin aut Rolf Fendel verfasserin aut Javier Ibáñez verfasserin aut Ulysse Ateba Ngoa verfasserin aut Jean Ronald Edoa verfasserin aut Bayodé Roméo Adégbité verfasserin aut Yabo Josiane Honkpéhédji verfasserin aut Jeannot Fréjus Zinsou verfasserin aut Aurore Bouyoukou Hounkpatin verfasserin aut Kabirou Moutairou verfasserin aut Andreas Homoet verfasserin aut Meral Esen verfasserin aut Andrea Kreidenweiss verfasserin aut Stephen L Hoffman verfasserin aut Michael Theisen verfasserin aut Adrian J F Luty verfasserin aut Bertrand Lell verfasserin aut Selidji Todagbe Agnandji verfasserin aut Ghyslain Mombo-Ngoma verfasserin aut Michael Ramharter verfasserin aut Peter Kremsner verfasserin aut Benjamin Mordmüller verfasserin aut Ayôla Akim Adegnika verfasserin aut In PLoS Neglected Tropical Diseases Public Library of Science (PLoS), 2008 15(2021), 6, p e0009361 (DE-627)568915356 (DE-600)2429704-5 19352735 nnns volume:15 year:2021 number:6, p e0009361 https://doi.org/10.1371/journal.pntd.0009361 kostenfrei https://doaj.org/article/bb9e94c7a35042c8863884855ee8d7a3 kostenfrei https://doi.org/10.1371/journal.pntd.0009361 kostenfrei https://doaj.org/toc/1935-2727 Journal toc kostenfrei https://doaj.org/toc/1935-2735 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2021 6, p e0009361 |
spelling |
10.1371/journal.pntd.0009361 doi (DE-627)DOAJ072459220 (DE-599)DOAJbb9e94c7a35042c8863884855ee8d7a3 DE-627 ger DE-627 rakwb eng RC955-962 RA1-1270 Odilon Nouatin verfasserin aut Exploratory analysis of the effect of helminth infection on the immunogenicity and efficacy of the asexual blood-stage malaria vaccine candidate GMZ2. 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <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. Arctic medicine. Tropical medicine Public aspects of medicine Juliana Boex Mengue verfasserin aut Jean Claude Dejon-Agobé verfasserin aut Rolf Fendel verfasserin aut Javier Ibáñez verfasserin aut Ulysse Ateba Ngoa verfasserin aut Jean Ronald Edoa verfasserin aut Bayodé Roméo Adégbité verfasserin aut Yabo Josiane Honkpéhédji verfasserin aut Jeannot Fréjus Zinsou verfasserin aut Aurore Bouyoukou Hounkpatin verfasserin aut Kabirou Moutairou verfasserin aut Andreas Homoet verfasserin aut Meral Esen verfasserin aut Andrea Kreidenweiss verfasserin aut Stephen L Hoffman verfasserin aut Michael Theisen verfasserin aut Adrian J F Luty verfasserin aut Bertrand Lell verfasserin aut Selidji Todagbe Agnandji verfasserin aut Ghyslain Mombo-Ngoma verfasserin aut Michael Ramharter verfasserin aut Peter Kremsner verfasserin aut Benjamin Mordmüller verfasserin aut Ayôla Akim Adegnika verfasserin aut In PLoS Neglected Tropical Diseases Public Library of Science (PLoS), 2008 15(2021), 6, p e0009361 (DE-627)568915356 (DE-600)2429704-5 19352735 nnns volume:15 year:2021 number:6, p e0009361 https://doi.org/10.1371/journal.pntd.0009361 kostenfrei https://doaj.org/article/bb9e94c7a35042c8863884855ee8d7a3 kostenfrei https://doi.org/10.1371/journal.pntd.0009361 kostenfrei https://doaj.org/toc/1935-2727 Journal toc kostenfrei https://doaj.org/toc/1935-2735 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2021 6, p e0009361 |
allfields_unstemmed |
10.1371/journal.pntd.0009361 doi (DE-627)DOAJ072459220 (DE-599)DOAJbb9e94c7a35042c8863884855ee8d7a3 DE-627 ger DE-627 rakwb eng RC955-962 RA1-1270 Odilon Nouatin verfasserin aut Exploratory analysis of the effect of helminth infection on the immunogenicity and efficacy of the asexual blood-stage malaria vaccine candidate GMZ2. 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <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. Arctic medicine. Tropical medicine Public aspects of medicine Juliana Boex Mengue verfasserin aut Jean Claude Dejon-Agobé verfasserin aut Rolf Fendel verfasserin aut Javier Ibáñez verfasserin aut Ulysse Ateba Ngoa verfasserin aut Jean Ronald Edoa verfasserin aut Bayodé Roméo Adégbité verfasserin aut Yabo Josiane Honkpéhédji verfasserin aut Jeannot Fréjus Zinsou verfasserin aut Aurore Bouyoukou Hounkpatin verfasserin aut Kabirou Moutairou verfasserin aut Andreas Homoet verfasserin aut Meral Esen verfasserin aut Andrea Kreidenweiss verfasserin aut Stephen L Hoffman verfasserin aut Michael Theisen verfasserin aut Adrian J F Luty verfasserin aut Bertrand Lell verfasserin aut Selidji Todagbe Agnandji verfasserin aut Ghyslain Mombo-Ngoma verfasserin aut Michael Ramharter verfasserin aut Peter Kremsner verfasserin aut Benjamin Mordmüller verfasserin aut Ayôla Akim Adegnika verfasserin aut In PLoS Neglected Tropical Diseases Public Library of Science (PLoS), 2008 15(2021), 6, p e0009361 (DE-627)568915356 (DE-600)2429704-5 19352735 nnns volume:15 year:2021 number:6, p e0009361 https://doi.org/10.1371/journal.pntd.0009361 kostenfrei https://doaj.org/article/bb9e94c7a35042c8863884855ee8d7a3 kostenfrei https://doi.org/10.1371/journal.pntd.0009361 kostenfrei https://doaj.org/toc/1935-2727 Journal toc kostenfrei https://doaj.org/toc/1935-2735 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2021 6, p e0009361 |
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10.1371/journal.pntd.0009361 doi (DE-627)DOAJ072459220 (DE-599)DOAJbb9e94c7a35042c8863884855ee8d7a3 DE-627 ger DE-627 rakwb eng RC955-962 RA1-1270 Odilon Nouatin verfasserin aut Exploratory analysis of the effect of helminth infection on the immunogenicity and efficacy of the asexual blood-stage malaria vaccine candidate GMZ2. 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <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. Arctic medicine. Tropical medicine Public aspects of medicine Juliana Boex Mengue verfasserin aut Jean Claude Dejon-Agobé verfasserin aut Rolf Fendel verfasserin aut Javier Ibáñez verfasserin aut Ulysse Ateba Ngoa verfasserin aut Jean Ronald Edoa verfasserin aut Bayodé Roméo Adégbité verfasserin aut Yabo Josiane Honkpéhédji verfasserin aut Jeannot Fréjus Zinsou verfasserin aut Aurore Bouyoukou Hounkpatin verfasserin aut Kabirou Moutairou verfasserin aut Andreas Homoet verfasserin aut Meral Esen verfasserin aut Andrea Kreidenweiss verfasserin aut Stephen L Hoffman verfasserin aut Michael Theisen verfasserin aut Adrian J F Luty verfasserin aut Bertrand Lell verfasserin aut Selidji Todagbe Agnandji verfasserin aut Ghyslain Mombo-Ngoma verfasserin aut Michael Ramharter verfasserin aut Peter Kremsner verfasserin aut Benjamin Mordmüller verfasserin aut Ayôla Akim Adegnika verfasserin aut In PLoS Neglected Tropical Diseases Public Library of Science (PLoS), 2008 15(2021), 6, p e0009361 (DE-627)568915356 (DE-600)2429704-5 19352735 nnns volume:15 year:2021 number:6, p e0009361 https://doi.org/10.1371/journal.pntd.0009361 kostenfrei https://doaj.org/article/bb9e94c7a35042c8863884855ee8d7a3 kostenfrei https://doi.org/10.1371/journal.pntd.0009361 kostenfrei https://doaj.org/toc/1935-2727 Journal toc kostenfrei https://doaj.org/toc/1935-2735 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2021 6, p e0009361 |
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10.1371/journal.pntd.0009361 doi (DE-627)DOAJ072459220 (DE-599)DOAJbb9e94c7a35042c8863884855ee8d7a3 DE-627 ger DE-627 rakwb eng RC955-962 RA1-1270 Odilon Nouatin verfasserin aut Exploratory analysis of the effect of helminth infection on the immunogenicity and efficacy of the asexual blood-stage malaria vaccine candidate GMZ2. 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <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. Arctic medicine. Tropical medicine Public aspects of medicine Juliana Boex Mengue verfasserin aut Jean Claude Dejon-Agobé verfasserin aut Rolf Fendel verfasserin aut Javier Ibáñez verfasserin aut Ulysse Ateba Ngoa verfasserin aut Jean Ronald Edoa verfasserin aut Bayodé Roméo Adégbité verfasserin aut Yabo Josiane Honkpéhédji verfasserin aut Jeannot Fréjus Zinsou verfasserin aut Aurore Bouyoukou Hounkpatin verfasserin aut Kabirou Moutairou verfasserin aut Andreas Homoet verfasserin aut Meral Esen verfasserin aut Andrea Kreidenweiss verfasserin aut Stephen L Hoffman verfasserin aut Michael Theisen verfasserin aut Adrian J F Luty verfasserin aut Bertrand Lell verfasserin aut Selidji Todagbe Agnandji verfasserin aut Ghyslain Mombo-Ngoma verfasserin aut Michael Ramharter verfasserin aut Peter Kremsner verfasserin aut Benjamin Mordmüller verfasserin aut Ayôla Akim Adegnika verfasserin aut In PLoS Neglected Tropical Diseases Public Library of Science (PLoS), 2008 15(2021), 6, p e0009361 (DE-627)568915356 (DE-600)2429704-5 19352735 nnns volume:15 year:2021 number:6, p e0009361 https://doi.org/10.1371/journal.pntd.0009361 kostenfrei https://doaj.org/article/bb9e94c7a35042c8863884855ee8d7a3 kostenfrei https://doi.org/10.1371/journal.pntd.0009361 kostenfrei https://doaj.org/toc/1935-2727 Journal toc kostenfrei https://doaj.org/toc/1935-2735 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2021 6, p e0009361 |
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Odilon Nouatin @@aut@@ Juliana Boex Mengue @@aut@@ Jean Claude Dejon-Agobé @@aut@@ Rolf Fendel @@aut@@ Javier Ibáñez @@aut@@ Ulysse Ateba Ngoa @@aut@@ Jean Ronald Edoa @@aut@@ Bayodé Roméo Adégbité @@aut@@ Yabo Josiane Honkpéhédji @@aut@@ Jeannot Fréjus Zinsou @@aut@@ Aurore Bouyoukou Hounkpatin @@aut@@ Kabirou Moutairou @@aut@@ Andreas Homoet @@aut@@ Meral Esen @@aut@@ Andrea Kreidenweiss @@aut@@ Stephen L Hoffman @@aut@@ Michael Theisen @@aut@@ Adrian J F Luty @@aut@@ Bertrand Lell @@aut@@ Selidji Todagbe Agnandji @@aut@@ Ghyslain Mombo-Ngoma @@aut@@ Michael Ramharter @@aut@@ Peter Kremsner @@aut@@ Benjamin Mordmüller @@aut@@ Ayôla Akim Adegnika @@aut@@ |
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RC955-962 RA1-1270 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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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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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 |
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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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Exploratory analysis of the effect of helminth infection on the immunogenicity and efficacy of the asexual blood-stage malaria vaccine candidate GMZ2. |
abstract |
<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. |
abstractGer |
<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. |
abstract_unstemmed |
<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. |
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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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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 |
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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 |
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10.1371/journal.pntd.0009361 |
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2024-07-04T01:09:26.747Z |
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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.</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Arctic medicine. 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