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Effect of immune regulatory pathways after immunization with GMZ2 malaria vaccine candidate in healthy lifelong malaria-exposed adults

•Immunization increases sHLA-G and Treg levels.•Post immunization sHLA-G level decrease vaccine-specific antibody concentration.•Pre and post immunization Treg level decrease plasmablasts frequency.•High sHLA-G ratio is associated with risk of P. falciparum infection after CHMI. Despite appreciable... Full description

Journal Title: Vaccine 2020-06-02, Vol.38 (27), p.4263-4272
Main Author: Nouatin, Odilon
Other Authors: Ateba Ngoa, Ulysse , Ibáñez, Javier , Dejon-Agobe, Jean Claude , Mordmüller, Benjamin , Edoa, Jean Ronald , Mougeni, Fabrice , Brückner, Sina , Bouyoukou Hounkpatin, Aurore , Esen, Meral , Theisen, Michael , Moutairou, Kabirou , Hoffman, Stephen L , Issifou, Saadou , Luty, Adrian J.F , Loembe, Marguerite M , Agnandji, Selidji Todagbé , Lell, Bertrand , Kremsner, Peter G , Adegnika, Ayôla Akim
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
Publisher: Netherlands: Elsevier Ltd
ID: ISSN: 0264-410X
Link: https://www.ncbi.nlm.nih.gov/pubmed/32386747
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title: Effect of immune regulatory pathways after immunization with GMZ2 malaria vaccine candidate in healthy lifelong malaria-exposed adults
format: Article
creator:
  • Nouatin, Odilon
  • Ateba Ngoa, Ulysse
  • Ibáñez, Javier
  • Dejon-Agobe, Jean Claude
  • Mordmüller, Benjamin
  • Edoa, Jean Ronald
  • Mougeni, Fabrice
  • Brückner, Sina
  • Bouyoukou Hounkpatin, Aurore
  • Esen, Meral
  • Theisen, Michael
  • Moutairou, Kabirou
  • Hoffman, Stephen L
  • Issifou, Saadou
  • Luty, Adrian J.F
  • Loembe, Marguerite M
  • Agnandji, Selidji Todagbé
  • Lell, Bertrand
  • Kremsner, Peter G
  • Adegnika, Ayôla Akim
subjects:
  • Adult
  • Adults
  • Animals
  • Antibodies
  • Antibodies, Protozoan
  • Antigens
  • Antigens, Protozoan
  • Blood
  • CHMI
  • Exposure
  • GMZ2
  • Health care
  • Health risks
  • Histocompatibility antigen HLA
  • Humans
  • Immune response
  • Immunization
  • Immunogenicity
  • Immunoglobulin G
  • Infections
  • Inoculation
  • Leukocytes
  • Leukocytes, Mononuclear
  • Lymphocytes
  • Lymphocytes T
  • Malaria
  • Malaria Vaccines
  • Malaria, Falciparum - prevention & control
  • Pathways
  • Peripheral blood mononuclear cells
  • Plasmodium falciparum
  • Populations
  • Proteins
  • Public health
  • Rabies
  • Regulatory cells
  • Regulatory mechanisms (biology)
  • sHLA-G
  • Sporozoites
  • Studies
  • Vaccination
  • Vaccine efficacy
  • Vaccines
  • Vector-borne diseases
ispartof: Vaccine, 2020-06-02, Vol.38 (27), p.4263-4272
description: •Immunization increases sHLA-G and Treg levels.•Post immunization sHLA-G level decrease vaccine-specific antibody concentration.•Pre and post immunization Treg level decrease plasmablasts frequency.•High sHLA-G ratio is associated with risk of P. falciparum infection after CHMI. Despite appreciable immunogenicity in malaria-naive populations, many candidate malaria vaccines are considerably less immunogenic in malaria-exposed populations. This could reflect induction of immune regulatory mechanisms involving Human Leukocyte Antigen G (HLA-G), regulatory T (Treg), and regulatory B (Breg) cells. Here, we addressed the question whether there is correlation between these immune regulatory pathways and both plasmablast frequencies and vaccine-specific IgG concentrations. Fifty Gabonese adults with lifelong exposure to Plasmodium spp were randomized to receive three doses of either 30 µg or 100 µg GMZ2-CAF01, or 100 µg GMZ2-alum, or control vaccine (rabies vaccine) at 4-week intervals. Only plasma and peripheral blood mononuclear cells isolated from blood samples collected before (D0) and 28 days after the third vaccination (D84) of 35 participants were used to measure sHLA-G levels and anti-GMZ2 IgG concentrations, and to quantify Treg, Breg and plasmablast cells. Vaccine efficacy was assessed using controlled human malaria infection (CHMI) by direct venous inoculation of Plasmodium falciparum sporozoites (PfSPZ Challenge). The sHLA-G concentration increased from D0 to D84 in all GMZ2 vaccinated participants and in the control group, whereas Treg frequencies increased only in those receiving 30 µg or 100 µg GMZ2-CAF01. The sHLA-G level on D84 was associated with a decrease of the anti-GMZ2 IgG concentration, whereas Treg frequencies on D0 or on D84, and Breg frequency on D84 were associated with lower plasmablast frequencies. Importantly, having a D84:D0 ratio of sHLA-G above the median was associated with an increased risk of P. falciparum infection after sporozoites injection. Regulatory immune responses are induced following immunization. Stronger sHLA-G and Treg immune responses may suppress vaccine induced immune responses, and the magnitude of the sHLA-G response increased the risk of Plasmodium falciparum infection after CHMI. These findings could have implications for the design and testing of malaria vaccine candidates in semi-immune individuals.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0264-410X
fulltext: fulltext
issn:
  • 0264-410X
  • 1873-2518
url: Link


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titleEffect of immune regulatory pathways after immunization with GMZ2 malaria vaccine candidate in healthy lifelong malaria-exposed adults
sourceAlma/SFX Local Collection
creatorNouatin, Odilon ; Ateba Ngoa, Ulysse ; Ibáñez, Javier ; Dejon-Agobe, Jean Claude ; Mordmüller, Benjamin ; Edoa, Jean Ronald ; Mougeni, Fabrice ; Brückner, Sina ; Bouyoukou Hounkpatin, Aurore ; Esen, Meral ; Theisen, Michael ; Moutairou, Kabirou ; Hoffman, Stephen L ; Issifou, Saadou ; Luty, Adrian J.F ; Loembe, Marguerite M ; Agnandji, Selidji Todagbé ; Lell, Bertrand ; Kremsner, Peter G ; Adegnika, Ayôla Akim
creatorcontribNouatin, Odilon ; Ateba Ngoa, Ulysse ; Ibáñez, Javier ; Dejon-Agobe, Jean Claude ; Mordmüller, Benjamin ; Edoa, Jean Ronald ; Mougeni, Fabrice ; Brückner, Sina ; Bouyoukou Hounkpatin, Aurore ; Esen, Meral ; Theisen, Michael ; Moutairou, Kabirou ; Hoffman, Stephen L ; Issifou, Saadou ; Luty, Adrian J.F ; Loembe, Marguerite M ; Agnandji, Selidji Todagbé ; Lell, Bertrand ; Kremsner, Peter G ; Adegnika, Ayôla Akim
description•Immunization increases sHLA-G and Treg levels.•Post immunization sHLA-G level decrease vaccine-specific antibody concentration.•Pre and post immunization Treg level decrease plasmablasts frequency.•High sHLA-G ratio is associated with risk of P. falciparum infection after CHMI. Despite appreciable immunogenicity in malaria-naive populations, many candidate malaria vaccines are considerably less immunogenic in malaria-exposed populations. This could reflect induction of immune regulatory mechanisms involving Human Leukocyte Antigen G (HLA-G), regulatory T (Treg), and regulatory B (Breg) cells. Here, we addressed the question whether there is correlation between these immune regulatory pathways and both plasmablast frequencies and vaccine-specific IgG concentrations. Fifty Gabonese adults with lifelong exposure to Plasmodium spp were randomized to receive three doses of either 30 µg or 100 µg GMZ2-CAF01, or 100 µg GMZ2-alum, or control vaccine (rabies vaccine) at 4-week intervals. Only plasma and peripheral blood mononuclear cells isolated from blood samples collected before (D0) and 28 days after the third vaccination (D84) of 35 participants were used to measure sHLA-G levels and anti-GMZ2 IgG concentrations, and to quantify Treg, Breg and plasmablast cells. Vaccine efficacy was assessed using controlled human malaria infection (CHMI) by direct venous inoculation of Plasmodium falciparum sporozoites (PfSPZ Challenge). The sHLA-G concentration increased from D0 to D84 in all GMZ2 vaccinated participants and in the control group, whereas Treg frequencies increased only in those receiving 30 µg or 100 µg GMZ2-CAF01. The sHLA-G level on D84 was associated with a decrease of the anti-GMZ2 IgG concentration, whereas Treg frequencies on D0 or on D84, and Breg frequency on D84 were associated with lower plasmablast frequencies. Importantly, having a D84:D0 ratio of sHLA-G above the median was associated with an increased risk of P. falciparum infection after sporozoites injection. Regulatory immune responses are induced following immunization. Stronger sHLA-G and Treg immune responses may suppress vaccine induced immune responses, and the magnitude of the sHLA-G response increased the risk of Plasmodium falciparum infection after CHMI. These findings could have implications for the design and testing of malaria vaccine candidates in semi-immune individuals.
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1EISSN: 1873-2518
2DOI: 10.1016/j.vaccine.2020.04.046
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languageeng
publisherNetherlands: Elsevier Ltd
subjectAdult ; Adults ; Animals ; Antibodies ; Antibodies, Protozoan ; Antigens ; Antigens, Protozoan ; Blood ; CHMI ; Exposure ; GMZ2 ; Health care ; Health risks ; Histocompatibility antigen HLA ; Humans ; Immune response ; Immunization ; Immunogenicity ; Immunoglobulin G ; Infections ; Inoculation ; Leukocytes ; Leukocytes, Mononuclear ; Lymphocytes ; Lymphocytes T ; Malaria ; Malaria Vaccines ; Malaria, Falciparum - prevention & control ; Pathways ; Peripheral blood mononuclear cells ; Plasmodium falciparum ; Populations ; Proteins ; Public health ; Rabies ; Regulatory cells ; Regulatory mechanisms (biology) ; sHLA-G ; Sporozoites ; Studies ; Vaccination ; Vaccine efficacy ; Vaccines ; Vector-borne diseases
ispartofVaccine, 2020-06-02, Vol.38 (27), p.4263-4272
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0Nouatin, Odilon
1Ateba Ngoa, Ulysse
2Ibáñez, Javier
3Dejon-Agobe, Jean Claude
4Mordmüller, Benjamin
5Edoa, Jean Ronald
6Mougeni, Fabrice
7Brückner, Sina
8Bouyoukou Hounkpatin, Aurore
9Esen, Meral
10Theisen, Michael
11Moutairou, Kabirou
12Hoffman, Stephen L
13Issifou, Saadou
14Luty, Adrian J.F
15Loembe, Marguerite M
16Agnandji, Selidji Todagbé
17Lell, Bertrand
18Kremsner, Peter G
19Adegnika, Ayôla Akim
title
0Effect of immune regulatory pathways after immunization with GMZ2 malaria vaccine candidate in healthy lifelong malaria-exposed adults
1Vaccine
addtitleVaccine
description•Immunization increases sHLA-G and Treg levels.•Post immunization sHLA-G level decrease vaccine-specific antibody concentration.•Pre and post immunization Treg level decrease plasmablasts frequency.•High sHLA-G ratio is associated with risk of P. falciparum infection after CHMI. Despite appreciable immunogenicity in malaria-naive populations, many candidate malaria vaccines are considerably less immunogenic in malaria-exposed populations. This could reflect induction of immune regulatory mechanisms involving Human Leukocyte Antigen G (HLA-G), regulatory T (Treg), and regulatory B (Breg) cells. Here, we addressed the question whether there is correlation between these immune regulatory pathways and both plasmablast frequencies and vaccine-specific IgG concentrations. Fifty Gabonese adults with lifelong exposure to Plasmodium spp were randomized to receive three doses of either 30 µg or 100 µg GMZ2-CAF01, or 100 µg GMZ2-alum, or control vaccine (rabies vaccine) at 4-week intervals. Only plasma and peripheral blood mononuclear cells isolated from blood samples collected before (D0) and 28 days after the third vaccination (D84) of 35 participants were used to measure sHLA-G levels and anti-GMZ2 IgG concentrations, and to quantify Treg, Breg and plasmablast cells. Vaccine efficacy was assessed using controlled human malaria infection (CHMI) by direct venous inoculation of Plasmodium falciparum sporozoites (PfSPZ Challenge). The sHLA-G concentration increased from D0 to D84 in all GMZ2 vaccinated participants and in the control group, whereas Treg frequencies increased only in those receiving 30 µg or 100 µg GMZ2-CAF01. The sHLA-G level on D84 was associated with a decrease of the anti-GMZ2 IgG concentration, whereas Treg frequencies on D0 or on D84, and Breg frequency on D84 were associated with lower plasmablast frequencies. Importantly, having a D84:D0 ratio of sHLA-G above the median was associated with an increased risk of P. falciparum infection after sporozoites injection. Regulatory immune responses are induced following immunization. Stronger sHLA-G and Treg immune responses may suppress vaccine induced immune responses, and the magnitude of the sHLA-G response increased the risk of Plasmodium falciparum infection after CHMI. These findings could have implications for the design and testing of malaria vaccine candidates in semi-immune individuals.
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23Lymphocytes
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25Malaria
26Malaria Vaccines
27Malaria, Falciparum - prevention & control
28Pathways
29Peripheral blood mononuclear cells
30Plasmodium falciparum
31Populations
32Proteins
33Public health
34Rabies
35Regulatory cells
36Regulatory mechanisms (biology)
37sHLA-G
38Sporozoites
39Studies
40Vaccination
41Vaccine efficacy
42Vaccines
43Vector-borne diseases
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1Ateba Ngoa, Ulysse
2Ibáñez, Javier
3Dejon-Agobe, Jean Claude
4Mordmüller, Benjamin
5Edoa, Jean Ronald
6Mougeni, Fabrice
7Brückner, Sina
8Bouyoukou Hounkpatin, Aurore
9Esen, Meral
10Theisen, Michael
11Moutairou, Kabirou
12Hoffman, Stephen L
13Issifou, Saadou
14Luty, Adrian J.F
15Loembe, Marguerite M
16Agnandji, Selidji Todagbé
17Lell, Bertrand
18Kremsner, Peter G
19Adegnika, Ayôla Akim
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titleEffect of immune regulatory pathways after immunization with GMZ2 malaria vaccine candidate in healthy lifelong malaria-exposed adults
authorNouatin, Odilon ; Ateba Ngoa, Ulysse ; Ibáñez, Javier ; Dejon-Agobe, Jean Claude ; Mordmüller, Benjamin ; Edoa, Jean Ronald ; Mougeni, Fabrice ; Brückner, Sina ; Bouyoukou Hounkpatin, Aurore ; Esen, Meral ; Theisen, Michael ; Moutairou, Kabirou ; Hoffman, Stephen L ; Issifou, Saadou ; Luty, Adrian J.F ; Loembe, Marguerite M ; Agnandji, Selidji Todagbé ; Lell, Bertrand ; Kremsner, Peter G ; Adegnika, Ayôla Akim
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31Populations
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33Public health
34Rabies
35Regulatory cells
36Regulatory mechanisms (biology)
37sHLA-G
38Sporozoites
39Studies
40Vaccination
41Vaccine efficacy
42Vaccines
43Vector-borne diseases
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0Nouatin, Odilon
1Ateba Ngoa, Ulysse
2Ibáñez, Javier
3Dejon-Agobe, Jean Claude
4Mordmüller, Benjamin
5Edoa, Jean Ronald
6Mougeni, Fabrice
7Brückner, Sina
8Bouyoukou Hounkpatin, Aurore
9Esen, Meral
10Theisen, Michael
11Moutairou, Kabirou
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13Issifou, Saadou
14Luty, Adrian J.F
15Loembe, Marguerite M
16Agnandji, Selidji Todagbé
17Lell, Bertrand
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atitleEffect of immune regulatory pathways after immunization with GMZ2 malaria vaccine candidate in healthy lifelong malaria-exposed adults
jtitleVaccine
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notes
0Authors’ contributions
1Conceived and designed the experiments: AAA, BM, AJFL, ME, ON, UAN, JI
2Writing - Original Draft Odilon Nouatin
3Project administration Ayôla Akim Adegnika, Benjamin Mordmüller, Meral Esen
4Visualization All authors
5Methodology Ayôla Akim Adegnika, Benjamin Mordmüller, Adrian J. F. Luty, Meral Esen, Odilon Nouatin, Ulysse Ateba Ngoa, Javier Ibáñez
6Investigation Ayôla Akim Adegnika, Benjamin Mordmüller, Odilon Nouatin, Ulysse Ateba Ngoa, Jean Claude Dejon-Agobe, Jean Ronald Edoa, Kabirou Moutairou, Saadou Issifou, Bertrand Lell, Peter G. Kremsner
7Data Curation Ayôla Akim Adegnika, Benjamin Mordmüller
8Writing - Review & Editing All authors
9Draft the first manuscript: ON
10Performed the experiments: ON, JI, UAN
11Revised: ON, UAN, JI, JCDA, BM, JRE, FM, SB, ABH, ME, MT, AJFL, KM, SLH, SI, MML, STA, BL, PK, AAA
12Resources Ayôla Akim Adegnika, Benjamin Mordmüller, Meral Esen, Michael Theisen, Stephen L. Hoffman, Bertrand Lell, Peter G. Kremsner
13Funding acquisition Ayôla Akim Adegnika, Benjamin Mordmüller, Bertrand Lell, Peter G. Kremsner
14Credit Author Statement
15Conceptualization Ayôla Akim Adegnika, Benjamin Mordmüller, Adrian J. F. Luty, Meral Esen, Odilon Nouatin, Ulysse Ateba Ngoa, Javier Ibáñez
16Supervision Ayôla Akim Adegnika, Benjamin Mordmüller
17Formal analysis Odilon Nouatin, Fabrice Mougeni
18Validation Ayôla Akim Adegnika, Benjamin Mordmüller, Bertrand Lell
19Analyzed the data: ON, FM
20Contributed reagents/materials: AAA, BM, ME, MT, SLH, BL, PGK
21Software Odilon Nouatin, Fabrice Mougeni, Ayôla Akim Adegnika
abstract•Immunization increases sHLA-G and Treg levels.•Post immunization sHLA-G level decrease vaccine-specific antibody concentration.•Pre and post immunization Treg level decrease plasmablasts frequency.•High sHLA-G ratio is associated with risk of P. falciparum infection after CHMI. Despite appreciable immunogenicity in malaria-naive populations, many candidate malaria vaccines are considerably less immunogenic in malaria-exposed populations. This could reflect induction of immune regulatory mechanisms involving Human Leukocyte Antigen G (HLA-G), regulatory T (Treg), and regulatory B (Breg) cells. Here, we addressed the question whether there is correlation between these immune regulatory pathways and both plasmablast frequencies and vaccine-specific IgG concentrations. Fifty Gabonese adults with lifelong exposure to Plasmodium spp were randomized to receive three doses of either 30 µg or 100 µg GMZ2-CAF01, or 100 µg GMZ2-alum, or control vaccine (rabies vaccine) at 4-week intervals. Only plasma and peripheral blood mononuclear cells isolated from blood samples collected before (D0) and 28 days after the third vaccination (D84) of 35 participants were used to measure sHLA-G levels and anti-GMZ2 IgG concentrations, and to quantify Treg, Breg and plasmablast cells. Vaccine efficacy was assessed using controlled human malaria infection (CHMI) by direct venous inoculation of Plasmodium falciparum sporozoites (PfSPZ Challenge). The sHLA-G concentration increased from D0 to D84 in all GMZ2 vaccinated participants and in the control group, whereas Treg frequencies increased only in those receiving 30 µg or 100 µg GMZ2-CAF01. The sHLA-G level on D84 was associated with a decrease of the anti-GMZ2 IgG concentration, whereas Treg frequencies on D0 or on D84, and Breg frequency on D84 were associated with lower plasmablast frequencies. Importantly, having a D84:D0 ratio of sHLA-G above the median was associated with an increased risk of P. falciparum infection after sporozoites injection. Regulatory immune responses are induced following immunization. Stronger sHLA-G and Treg immune responses may suppress vaccine induced immune responses, and the magnitude of the sHLA-G response increased the risk of Plasmodium falciparum infection after CHMI. These findings could have implications for the design and testing of malaria vaccine candidates in semi-immune individuals.
copNetherlands
pubElsevier Ltd
pmid32386747
doi10.1016/j.vaccine.2020.04.046
oafree_for_read