schliessen

Filtern

 

Bibliotheken

Towards large-scale identification of HLA-restricted T cell epitopes from four vaccine candidate antigens in a malaria endemic community in Ghana

•Plasmodium CSP and AMA1 exhibited more T cell epitopes compared to TRAP and CelTOS.•The most frequent T cell responses to the four antigens were to the CSP C-terminal.•Frequency of IFN-γ responses were 6-fold higher than that of granzyme B responses. Sterile protection against clinical malaria has... Full description

Journal Title: Vaccine 2022, Vol.40 (5), p.757-764
Main Author: Kusi, Kwadwo Asamoah
Other Authors: Ofori, Ebenezer Addo , Akyea-Mensah, Kwadwo , Kyei-Baafour, Eric , Frimpong, Augustina , Ennuson, Nana Aba , Belmonte, Maria , Ganeshan, Harini , Huang, Jun , Amoah, Linda Eva , Villasante, Eileen , Sedegah, Martha
Format: Electronic Article Electronic Article
Language: English
Subjects:
R&D
Publisher: Netherlands: Elsevier Ltd
ID: ISSN: 0264-410X
Link: https://www.ncbi.nlm.nih.gov/pubmed/34969544
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: cdi_proquest_miscellaneous_2615920072
title: Towards large-scale identification of HLA-restricted T cell epitopes from four vaccine candidate antigens in a malaria endemic community in Ghana
format: Article
creator:
  • Kusi, Kwadwo Asamoah
  • Ofori, Ebenezer Addo
  • Akyea-Mensah, Kwadwo
  • Kyei-Baafour, Eric
  • Frimpong, Augustina
  • Ennuson, Nana Aba
  • Belmonte, Maria
  • Ganeshan, Harini
  • Huang, Jun
  • Amoah, Linda Eva
  • Villasante, Eileen
  • Sedegah, Martha
subjects:
  • Acid phosphatase (tartrate-resistant)
  • Adults
  • Amino acids
  • Analysis
  • Animal models
  • Animals
  • Antigenic determinants
  • Antigens
  • Antigens, Protozoan
  • Apical membrane antigen 1
  • CD8 antigen
  • Chloroquine
  • Circumsporozoite protein
  • Cryopreservation
  • Epitopes
  • Epitopes, T-Lymphocyte
  • FluoroSpot
  • Ghana
  • Granzyme B
  • Histocompatibility antigen HLA
  • Human subjects
  • Humans
  • IFN-γ
  • Immunization
  • Infections
  • Leukocytes, Mononuclear
  • Liver
  • Lymphocytes
  • Lymphocytes T
  • Malaria
  • Malaria vaccine
  • Malaria Vaccines
  • Malaria, Falciparum - prevention & control
  • Medical research
  • Parasites
  • Peptides
  • Peripheral blood mononuclear cells
  • Plasmodium falciparum
  • Pools
  • Prophylaxis
  • Proteins
  • Protozoan Proteins
  • R&D
  • Radiation
  • Research & development
  • Sporozoites
  • T cells
  • Thrombospondin
  • Vaccines
  • Vector-borne diseases
  • Zygotes
  • γ-Interferon
ispartof: Vaccine, 2022, Vol.40 (5), p.757-764
description: •Plasmodium CSP and AMA1 exhibited more T cell epitopes compared to TRAP and CelTOS.•The most frequent T cell responses to the four antigens were to the CSP C-terminal.•Frequency of IFN-γ responses were 6-fold higher than that of granzyme B responses. Sterile protection against clinical malaria has been achieved in animal models and experimental human challenge studies involving immunization with radiation attenuated Plasmodium falciparum sporozoite vaccines as well as by live sporozoites under chloroquine prophylaxis. Parasite-specific IFN-γ and granzyme B-secreting CD8 + T cells have been identified as key mediators of protection. Although the exact parasite targets of protective CD8 + T cell responses are not fully defined, responses against a handful of vaccine candidate antigens have been associated with protection. Identifying the T cell targets in these antigens will facilitate the development of simpler, cost-effective, and efficacious next generation multi-epitope vaccines. The aim of this study was to identify immunodominant portions of four malaria vaccine candidate antigens using peripheral blood mononuclear cells (PBMCs) from adults with life-long exposure to malaria parasites. Cryopreserved PBMCs from 291 HLA-typed subjects were stimulated with pools of overlapping 15mer peptides spanning the entire sequences of P. falciparum circumsporozoite protein (CSP, 9 pools), apical membrane antigen 1 (AMA1, 12 pools), thrombospondin related anonymous protein (TRAP, 6 pools) and cell traversal for ookinetes and sporozoites (CelTOS, 4 pools) in FluoroSpot assays. 125 of 291 subjects made IFN-γ responses to 30 of the 31 peptide pools tested and 22 of 291 made granzyme B responses, with 20 making dual responses. The most frequent responses were to the CSP C-terminal region and the least frequent responses were to TRAP and CelTOS. There was no association between FluoroSpot responses and active malaria infection, detected by either microscopy, RDT, or PCR. In conclusion, CSP and AMA1 have relatively higher numbers of epitopes that trigger IFN-γ and granzyme B-secreting T cells in adults with life-long malaria parasite exposure compared to the other two antigens tested, and highlights the continued relevance of these two antigens as vaccine candidates.
language: eng
source:
identifier: ISSN: 0264-410X
fulltext: no_fulltext
issn:
  • 0264-410X
  • 1873-2518
url: Link


@attributes
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
RANK2.6110663
LOCALfalse
PrimoNMBib
record
control
sourceidgale_proqu
recordidTN_cdi_proquest_miscellaneous_2615920072
sourceformatXML
sourcesystemPC
galeidA690121940
sourcerecordidA690121940
originalsourceidFETCH-LOGICAL-c372t-6329bf8a51dcc5b0775a0f567ac16d542f9a86b146d67b0de685e2aa81657b610
addsrcrecordideNqFkcGO0zAQhiMEYsvCI4AsceGSYDuxk5xQtYJdpEpcisTNmtjj4iqxi53sah-DN8ahhQMX5IMl-_tn5p-_KF4zWjHK5PtjdQ9aO48Vp5xVjFe04U-KDevauuSCdU-LDeWyKRtGv10VL1I6UkpFzfrnxVXd9LIXTbMpfu7DA0STyAjxgGXSMCJxBv3srNMwu-BJsORuty0jpjk6PaMhe6JxHAme3BxOmIiNYSI2LJFchiIavHEGZiSQSx3QJ-I8ATJBbuSAoDc4OU10mKbFu_lx_b79Dh5eFs8sjAlfXe7r4uunj_ubu3L35fbzzXZX6rrlcylr3g-2A8GM1mKgbSuAWiFb0Ewa0XDbQycH1kgj24EalJ1ADtAxKdpBMnpdvDvXPcXwY8ne1OTSags8hiUpLpnoOaUtz-jbf9Bj9urzdJnirKeM1itVnalD3qFy3oY5gs7nt9Pg0br8vpUZz5qGZoE4C3QMKUW06hTdBPFRMarWkNVRXfap1pAV4yqHnHVvLuMsw4Tmr-pPqhn4cAYw7-_eYVRJO_QajYuoZ2WC-0-LX78Nu0U
sourcetypeAggregation Database
isCDItrue
recordtypearticle
pqid2621901032
display
typearticle
titleTowards large-scale identification of HLA-restricted T cell epitopes from four vaccine candidate antigens in a malaria endemic community in Ghana
creatorKusi, Kwadwo Asamoah ; Ofori, Ebenezer Addo ; Akyea-Mensah, Kwadwo ; Kyei-Baafour, Eric ; Frimpong, Augustina ; Ennuson, Nana Aba ; Belmonte, Maria ; Ganeshan, Harini ; Huang, Jun ; Amoah, Linda Eva ; Villasante, Eileen ; Sedegah, Martha
creatorcontribKusi, Kwadwo Asamoah ; Ofori, Ebenezer Addo ; Akyea-Mensah, Kwadwo ; Kyei-Baafour, Eric ; Frimpong, Augustina ; Ennuson, Nana Aba ; Belmonte, Maria ; Ganeshan, Harini ; Huang, Jun ; Amoah, Linda Eva ; Villasante, Eileen ; Sedegah, Martha
description•Plasmodium CSP and AMA1 exhibited more T cell epitopes compared to TRAP and CelTOS.•The most frequent T cell responses to the four antigens were to the CSP C-terminal.•Frequency of IFN-γ responses were 6-fold higher than that of granzyme B responses. Sterile protection against clinical malaria has been achieved in animal models and experimental human challenge studies involving immunization with radiation attenuated Plasmodium falciparum sporozoite vaccines as well as by live sporozoites under chloroquine prophylaxis. Parasite-specific IFN-γ and granzyme B-secreting CD8 + T cells have been identified as key mediators of protection. Although the exact parasite targets of protective CD8 + T cell responses are not fully defined, responses against a handful of vaccine candidate antigens have been associated with protection. Identifying the T cell targets in these antigens will facilitate the development of simpler, cost-effective, and efficacious next generation multi-epitope vaccines. The aim of this study was to identify immunodominant portions of four malaria vaccine candidate antigens using peripheral blood mononuclear cells (PBMCs) from adults with life-long exposure to malaria parasites. Cryopreserved PBMCs from 291 HLA-typed subjects were stimulated with pools of overlapping 15mer peptides spanning the entire sequences of P. falciparum circumsporozoite protein (CSP, 9 pools), apical membrane antigen 1 (AMA1, 12 pools), thrombospondin related anonymous protein (TRAP, 6 pools) and cell traversal for ookinetes and sporozoites (CelTOS, 4 pools) in FluoroSpot assays. 125 of 291 subjects made IFN-γ responses to 30 of the 31 peptide pools tested and 22 of 291 made granzyme B responses, with 20 making dual responses. The most frequent responses were to the CSP C-terminal region and the least frequent responses were to TRAP and CelTOS. There was no association between FluoroSpot responses and active malaria infection, detected by either microscopy, RDT, or PCR. In conclusion, CSP and AMA1 have relatively higher numbers of epitopes that trigger IFN-γ and granzyme B-secreting T cells in adults with life-long malaria parasite exposure compared to the other two antigens tested, and highlights the continued relevance of these two antigens as vaccine candidates.
identifier
0ISSN: 0264-410X
1EISSN: 1873-2518
2DOI: 10.1016/j.vaccine.2021.12.042
3PMID: 34969544
languageeng
publisherNetherlands: Elsevier Ltd
subjectAcid phosphatase (tartrate-resistant) ; Adults ; Amino acids ; Analysis ; Animal models ; Animals ; Antigenic determinants ; Antigens ; Antigens, Protozoan ; Apical membrane antigen 1 ; CD8 antigen ; Chloroquine ; Circumsporozoite protein ; Cryopreservation ; Epitopes ; Epitopes, T-Lymphocyte ; FluoroSpot ; Ghana ; Granzyme B ; Histocompatibility antigen HLA ; Human subjects ; Humans ; IFN-γ ; Immunization ; Infections ; Leukocytes, Mononuclear ; Liver ; Lymphocytes ; Lymphocytes T ; Malaria ; Malaria vaccine ; Malaria Vaccines ; Malaria, Falciparum - prevention & control ; Medical research ; Parasites ; Peptides ; Peripheral blood mononuclear cells ; Plasmodium falciparum ; Pools ; Prophylaxis ; Proteins ; Protozoan Proteins ; R&D ; Radiation ; Research & development ; Sporozoites ; T cells ; Thrombospondin ; Vaccines ; Vector-borne diseases ; Zygotes ; γ-Interferon
ispartofVaccine, 2022, Vol.40 (5), p.757-764
rights
02021 The Author(s)
1Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
2COPYRIGHT 2022 Elsevier B.V.
32021. The Author(s)
lds50peer_reviewed
oafree_for_read
citesFETCH-LOGICAL-c372t-6329bf8a51dcc5b0775a0f567ac16d542f9a86b146d67b0de685e2aa81657b610
links
openurl$$Topenurl_article
thumbnail$$Usyndetics_thumb_exl
backlink$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34969544$$D View this record in MEDLINE/PubMed
search
creatorcontrib
0Kusi, Kwadwo Asamoah
1Ofori, Ebenezer Addo
2Akyea-Mensah, Kwadwo
3Kyei-Baafour, Eric
4Frimpong, Augustina
5Ennuson, Nana Aba
6Belmonte, Maria
7Ganeshan, Harini
8Huang, Jun
9Amoah, Linda Eva
10Villasante, Eileen
11Sedegah, Martha
title
0Towards large-scale identification of HLA-restricted T cell epitopes from four vaccine candidate antigens in a malaria endemic community in Ghana
1Vaccine
addtitleVaccine
description•Plasmodium CSP and AMA1 exhibited more T cell epitopes compared to TRAP and CelTOS.•The most frequent T cell responses to the four antigens were to the CSP C-terminal.•Frequency of IFN-γ responses were 6-fold higher than that of granzyme B responses. Sterile protection against clinical malaria has been achieved in animal models and experimental human challenge studies involving immunization with radiation attenuated Plasmodium falciparum sporozoite vaccines as well as by live sporozoites under chloroquine prophylaxis. Parasite-specific IFN-γ and granzyme B-secreting CD8 + T cells have been identified as key mediators of protection. Although the exact parasite targets of protective CD8 + T cell responses are not fully defined, responses against a handful of vaccine candidate antigens have been associated with protection. Identifying the T cell targets in these antigens will facilitate the development of simpler, cost-effective, and efficacious next generation multi-epitope vaccines. The aim of this study was to identify immunodominant portions of four malaria vaccine candidate antigens using peripheral blood mononuclear cells (PBMCs) from adults with life-long exposure to malaria parasites. Cryopreserved PBMCs from 291 HLA-typed subjects were stimulated with pools of overlapping 15mer peptides spanning the entire sequences of P. falciparum circumsporozoite protein (CSP, 9 pools), apical membrane antigen 1 (AMA1, 12 pools), thrombospondin related anonymous protein (TRAP, 6 pools) and cell traversal for ookinetes and sporozoites (CelTOS, 4 pools) in FluoroSpot assays. 125 of 291 subjects made IFN-γ responses to 30 of the 31 peptide pools tested and 22 of 291 made granzyme B responses, with 20 making dual responses. The most frequent responses were to the CSP C-terminal region and the least frequent responses were to TRAP and CelTOS. There was no association between FluoroSpot responses and active malaria infection, detected by either microscopy, RDT, or PCR. In conclusion, CSP and AMA1 have relatively higher numbers of epitopes that trigger IFN-γ and granzyme B-secreting T cells in adults with life-long malaria parasite exposure compared to the other two antigens tested, and highlights the continued relevance of these two antigens as vaccine candidates.
subject
0Acid phosphatase (tartrate-resistant)
1Adults
2Amino acids
3Analysis
4Animal models
5Animals
6Antigenic determinants
7Antigens
8Antigens, Protozoan
9Apical membrane antigen 1
10CD8 antigen
11Chloroquine
12Circumsporozoite protein
13Cryopreservation
14Epitopes
15Epitopes, T-Lymphocyte
16FluoroSpot
17Ghana
18Granzyme B
19Histocompatibility antigen HLA
20Human subjects
21Humans
22IFN-γ
23Immunization
24Infections
25Leukocytes, Mononuclear
26Liver
27Lymphocytes
28Lymphocytes T
29Malaria
30Malaria vaccine
31Malaria Vaccines
32Malaria, Falciparum - prevention & control
33Medical research
34Parasites
35Peptides
36Peripheral blood mononuclear cells
37Plasmodium falciparum
38Pools
39Prophylaxis
40Proteins
41Protozoan Proteins
42R&D
43Radiation
44Research & development
45Sporozoites
46T cells
47Thrombospondin
48Vaccines
49Vector-borne diseases
50Zygotes
51γ-Interferon
issn
00264-410X
11873-2518
fulltextfalse
rsrctypearticle
creationdate2022
recordtypearticle
recordideNqFkcGO0zAQhiMEYsvCI4AsceGSYDuxk5xQtYJdpEpcisTNmtjj4iqxi53sah-DN8ahhQMX5IMl-_tn5p-_KF4zWjHK5PtjdQ9aO48Vp5xVjFe04U-KDevauuSCdU-LDeWyKRtGv10VL1I6UkpFzfrnxVXd9LIXTbMpfu7DA0STyAjxgGXSMCJxBv3srNMwu-BJsORuty0jpjk6PaMhe6JxHAme3BxOmIiNYSI2LJFchiIavHEGZiSQSx3QJ-I8ATJBbuSAoDc4OU10mKbFu_lx_b79Dh5eFs8sjAlfXe7r4uunj_ubu3L35fbzzXZX6rrlcylr3g-2A8GM1mKgbSuAWiFb0Ewa0XDbQycH1kgj24EalJ1ADtAxKdpBMnpdvDvXPcXwY8ne1OTSags8hiUpLpnoOaUtz-jbf9Bj9urzdJnirKeM1itVnalD3qFy3oY5gs7nt9Pg0br8vpUZz5qGZoE4C3QMKUW06hTdBPFRMarWkNVRXfap1pAV4yqHnHVvLuMsw4Tmr-pPqhn4cAYw7-_eYVRJO_QajYuoZ2WC-0-LX78Nu0U
startdate20220131
enddate20220131
creator
0Kusi, Kwadwo Asamoah
1Ofori, Ebenezer Addo
2Akyea-Mensah, Kwadwo
3Kyei-Baafour, Eric
4Frimpong, Augustina
5Ennuson, Nana Aba
6Belmonte, Maria
7Ganeshan, Harini
8Huang, Jun
9Amoah, Linda Eva
10Villasante, Eileen
11Sedegah, Martha
general
0Elsevier Ltd
1Elsevier B.V
2Elsevier Limited
scope
06I.
1AAFTH
2CGR
3CUY
4CVF
5ECM
6EIF
7NPM
8AAYXX
9CITATION
10BSHEE
113V.
127QL
137RV
147T2
157T5
167U9
177X7
187XB
1988C
2088E
218AO
228C1
238FE
248FH
258FI
268FJ
278FK
288G5
29ABUWG
30AZQEC
31BBNVY
32BENPR
33BHPHI
34C1K
35DWQXO
36FYUFA
37GHDGH
38GNUQQ
39GUQSH
40H94
41HCIFZ
42K9-
43K9.
44KB0
45LK8
46M0R
47M0S
48M0T
49M1P
50M2O
51M7N
52M7P
53MBDVC
54NAPCQ
55PQEST
56PQQKQ
57PQUKI
58Q9U
597X8
sort
creationdate20220131
titleTowards large-scale identification of HLA-restricted T cell epitopes from four vaccine candidate antigens in a malaria endemic community in Ghana
authorKusi, Kwadwo Asamoah ; Ofori, Ebenezer Addo ; Akyea-Mensah, Kwadwo ; Kyei-Baafour, Eric ; Frimpong, Augustina ; Ennuson, Nana Aba ; Belmonte, Maria ; Ganeshan, Harini ; Huang, Jun ; Amoah, Linda Eva ; Villasante, Eileen ; Sedegah, Martha
facets
frbrtype5
frbrgroupidcdi_FETCH-LOGICAL-c372t-6329bf8a51dcc5b0775a0f567ac16d542f9a86b146d67b0de685e2aa81657b610
rsrctypearticles
prefilterarticles
languageeng
creationdate2022
topic
0Acid phosphatase (tartrate-resistant)
1Adults
2Amino acids
3Analysis
4Animal models
5Animals
6Antigenic determinants
7Antigens
8Antigens, Protozoan
9Apical membrane antigen 1
10CD8 antigen
11Chloroquine
12Circumsporozoite protein
13Cryopreservation
14Epitopes
15Epitopes, T-Lymphocyte
16FluoroSpot
17Ghana
18Granzyme B
19Histocompatibility antigen HLA
20Human subjects
21Humans
22IFN-γ
23Immunization
24Infections
25Leukocytes, Mononuclear
26Liver
27Lymphocytes
28Lymphocytes T
29Malaria
30Malaria vaccine
31Malaria Vaccines
32Malaria, Falciparum - prevention & control
33Medical research
34Parasites
35Peptides
36Peripheral blood mononuclear cells
37Plasmodium falciparum
38Pools
39Prophylaxis
40Proteins
41Protozoan Proteins
42R&D
43Radiation
44Research & development
45Sporozoites
46T cells
47Thrombospondin
48Vaccines
49Vector-borne diseases
50Zygotes
51γ-Interferon
toplevelpeer_reviewed
creatorcontrib
0Kusi, Kwadwo Asamoah
1Ofori, Ebenezer Addo
2Akyea-Mensah, Kwadwo
3Kyei-Baafour, Eric
4Frimpong, Augustina
5Ennuson, Nana Aba
6Belmonte, Maria
7Ganeshan, Harini
8Huang, Jun
9Amoah, Linda Eva
10Villasante, Eileen
11Sedegah, Martha
collection
0ScienceDirect Open Access Titles
1Elsevier:ScienceDirect:Open Access
2Medline
3MEDLINE
4MEDLINE (Ovid)
5MEDLINE
6MEDLINE
7PubMed
8CrossRef
9Academic OneFile (A&I only)
10ProQuest Central (Corporate)
11Bacteriology Abstracts (Microbiology B)
12Nursing & Allied Health Database
13Health and Safety Science Abstracts (Full archive)
14Immunology Abstracts
15Virology and AIDS Abstracts
16Health & Medical Collection
17ProQuest Central (purchase pre-March 2016)
18Healthcare Administration Database (Alumni)
19Medical Database (Alumni Edition)
20ProQuest Pharma Collection
21Public Health Database
22ProQuest SciTech Collection
23ProQuest Natural Science Collection
24Hospital Premium Collection
25Hospital Premium Collection (Alumni Edition)
26ProQuest Central (Alumni) (purchase pre-March 2016)
27Research Library (Alumni Edition)
28ProQuest Central (Alumni Edition)
29ProQuest Central Essentials
30Biological Science Collection
31ProQuest Central
32Natural Science Collection
33Environmental Sciences and Pollution Management
34ProQuest Central Korea
35Health Research Premium Collection
36Health Research Premium Collection (Alumni)
37ProQuest Central Student
38Research Library Prep
39AIDS and Cancer Research Abstracts
40SciTech Premium Collection
41Consumer Health Database (Alumni Edition)
42ProQuest Health & Medical Complete (Alumni)
43Nursing & Allied Health Database (Alumni Edition)
44ProQuest Biological Science Collection
45Consumer Health Database
46Health & Medical Collection (Alumni Edition)
47Healthcare Administration Database
48Medical Database
49Research Library
50Algology Mycology and Protozoology Abstracts (Microbiology C)
51Biological Science Database
52Research Library (Corporate)
53Nursing & Allied Health Premium
54ProQuest One Academic Eastern Edition
55ProQuest One Academic
56ProQuest One Academic UKI Edition
57ProQuest Central Basic
58MEDLINE - Academic
jtitleVaccine
delivery
delcategoryRemote Search Resource
fulltextno_fulltext
addata
au
0Kusi, Kwadwo Asamoah
1Ofori, Ebenezer Addo
2Akyea-Mensah, Kwadwo
3Kyei-Baafour, Eric
4Frimpong, Augustina
5Ennuson, Nana Aba
6Belmonte, Maria
7Ganeshan, Harini
8Huang, Jun
9Amoah, Linda Eva
10Villasante, Eileen
11Sedegah, Martha
formatjournal
genrearticle
ristypeJOUR
atitleTowards large-scale identification of HLA-restricted T cell epitopes from four vaccine candidate antigens in a malaria endemic community in Ghana
jtitleVaccine
addtitleVaccine
date2022-01-31
risdate2022
volume40
issue5
spage757
epage764
pages757-764
issn0264-410X
eissn1873-2518
abstract•Plasmodium CSP and AMA1 exhibited more T cell epitopes compared to TRAP and CelTOS.•The most frequent T cell responses to the four antigens were to the CSP C-terminal.•Frequency of IFN-γ responses were 6-fold higher than that of granzyme B responses. Sterile protection against clinical malaria has been achieved in animal models and experimental human challenge studies involving immunization with radiation attenuated Plasmodium falciparum sporozoite vaccines as well as by live sporozoites under chloroquine prophylaxis. Parasite-specific IFN-γ and granzyme B-secreting CD8 + T cells have been identified as key mediators of protection. Although the exact parasite targets of protective CD8 + T cell responses are not fully defined, responses against a handful of vaccine candidate antigens have been associated with protection. Identifying the T cell targets in these antigens will facilitate the development of simpler, cost-effective, and efficacious next generation multi-epitope vaccines. The aim of this study was to identify immunodominant portions of four malaria vaccine candidate antigens using peripheral blood mononuclear cells (PBMCs) from adults with life-long exposure to malaria parasites. Cryopreserved PBMCs from 291 HLA-typed subjects were stimulated with pools of overlapping 15mer peptides spanning the entire sequences of P. falciparum circumsporozoite protein (CSP, 9 pools), apical membrane antigen 1 (AMA1, 12 pools), thrombospondin related anonymous protein (TRAP, 6 pools) and cell traversal for ookinetes and sporozoites (CelTOS, 4 pools) in FluoroSpot assays. 125 of 291 subjects made IFN-γ responses to 30 of the 31 peptide pools tested and 22 of 291 made granzyme B responses, with 20 making dual responses. The most frequent responses were to the CSP C-terminal region and the least frequent responses were to TRAP and CelTOS. There was no association between FluoroSpot responses and active malaria infection, detected by either microscopy, RDT, or PCR. In conclusion, CSP and AMA1 have relatively higher numbers of epitopes that trigger IFN-γ and granzyme B-secreting T cells in adults with life-long malaria parasite exposure compared to the other two antigens tested, and highlights the continued relevance of these two antigens as vaccine candidates.
copNetherlands
pubElsevier Ltd
pmid34969544
doi10.1016/j.vaccine.2021.12.042
oafree_for_read