Analysis of human B ‐cell responses following C h A d63‐ MVA MSP 1 and AMA 1 immunization and controlled malaria infection
Acquisition of non‐sterilizing natural immunity to P lasmodium falciparum malaria has been shown in low transmission areas following multiple exposures. However, conflicting data from endemic areas suggest that the parasite may interfere with the induction of effective B ‐cell responses. To date, th...
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Veröffentlicht in: | Immunology 2014-04, Vol.141 (4), p.628-644 |
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creator | Elias, Sean C. Choudhary, Prateek de Cassan, Simone C. Biswas, Sumi Collins, Katharine A. Halstead, Fenella D. Bliss, Carly M. Ewer, Katie J. Hodgson, Susanne H. Duncan, Christopher J. A. Hill, Adrian V. S. Draper, Simon J. |
description | Acquisition of non‐sterilizing natural immunity to
P
lasmodium falciparum
malaria has been shown in low transmission areas following multiple exposures. However, conflicting data from endemic areas suggest that the parasite may interfere with the induction of effective
B
‐cell responses. To date, the impact of blood‐stage parasite exposure on antigen‐specific
B
cells has not been reported following controlled human malaria infection (
CHMI
). Here we analysed human
B
‐cell responses in a series of
P
hase I/IIa clinical trials, which include
CHMI
, using candidate virus‐vectored vaccines encoding two blood‐stage antigens: merozoite surface protein 1 (
MSP
1) and apical membrane antigen 1 (
AMA
1). Previously vaccinated volunteers show boosting of pre‐existing antigen‐specific memory
B
‐cell (m
BC
) responses following
CHMI
. In contrast, unvaccinated malaria‐naive control volunteers developed an m
BC
response against
MSP
1 but not
AMA
1. Serum
I
g
G
correlated with the m
BC
response after booster vaccination but this relationship was less well maintained following
CHMI
. A significant reduction in peripheral
MSP
1‐specific m
BC
was observed at the point of diagnosis of blood‐stage infection. This was coincident with a reduction in peripheral blood
B
‐cell subsets expressing
CXCR
3 and elevated serum levels of interferon‐
γ
and
CXCL
9, suggesting migration away from the periphery. These
CHMI
data confirm that m
BC
and antibody responses can be induced and boosted by blood‐stage parasite exposure, in support of epidemiological studies on low‐level parasite exposure. |
doi_str_mv | 10.1111/imm.12226 |
format | Article |
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P
lasmodium falciparum
malaria has been shown in low transmission areas following multiple exposures. However, conflicting data from endemic areas suggest that the parasite may interfere with the induction of effective
B
‐cell responses. To date, the impact of blood‐stage parasite exposure on antigen‐specific
B
cells has not been reported following controlled human malaria infection (
CHMI
). Here we analysed human
B
‐cell responses in a series of
P
hase I/IIa clinical trials, which include
CHMI
, using candidate virus‐vectored vaccines encoding two blood‐stage antigens: merozoite surface protein 1 (
MSP
1) and apical membrane antigen 1 (
AMA
1). Previously vaccinated volunteers show boosting of pre‐existing antigen‐specific memory
B
‐cell (m
BC
) responses following
CHMI
. In contrast, unvaccinated malaria‐naive control volunteers developed an m
BC
response against
MSP
1 but not
AMA
1. Serum
I
g
G
correlated with the m
BC
response after booster vaccination but this relationship was less well maintained following
CHMI
. A significant reduction in peripheral
MSP
1‐specific m
BC
was observed at the point of diagnosis of blood‐stage infection. This was coincident with a reduction in peripheral blood
B
‐cell subsets expressing
CXCR
3 and elevated serum levels of interferon‐
γ
and
CXCL
9, suggesting migration away from the periphery. These
CHMI
data confirm that m
BC
and antibody responses can be induced and boosted by blood‐stage parasite exposure, in support of epidemiological studies on low‐level parasite exposure.</description><identifier>ISSN: 0019-2805</identifier><identifier>EISSN: 1365-2567</identifier><identifier>DOI: 10.1111/imm.12226</identifier><language>eng</language><ispartof>Immunology, 2014-04, Vol.141 (4), p.628-644</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c746-17cced0e0576230dfd94d04ed4b28ce716a1a265d00a3f8a8aebf442663b439f3</citedby><cites>FETCH-LOGICAL-c746-17cced0e0576230dfd94d04ed4b28ce716a1a265d00a3f8a8aebf442663b439f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids></links><search><creatorcontrib>Elias, Sean C.</creatorcontrib><creatorcontrib>Choudhary, Prateek</creatorcontrib><creatorcontrib>de Cassan, Simone C.</creatorcontrib><creatorcontrib>Biswas, Sumi</creatorcontrib><creatorcontrib>Collins, Katharine A.</creatorcontrib><creatorcontrib>Halstead, Fenella D.</creatorcontrib><creatorcontrib>Bliss, Carly M.</creatorcontrib><creatorcontrib>Ewer, Katie J.</creatorcontrib><creatorcontrib>Hodgson, Susanne H.</creatorcontrib><creatorcontrib>Duncan, Christopher J. A.</creatorcontrib><creatorcontrib>Hill, Adrian V. S.</creatorcontrib><creatorcontrib>Draper, Simon J.</creatorcontrib><title>Analysis of human B ‐cell responses following C h A d63‐ MVA MSP 1 and AMA 1 immunization and controlled malaria infection</title><title>Immunology</title><description>Acquisition of non‐sterilizing natural immunity to
P
lasmodium falciparum
malaria has been shown in low transmission areas following multiple exposures. However, conflicting data from endemic areas suggest that the parasite may interfere with the induction of effective
B
‐cell responses. To date, the impact of blood‐stage parasite exposure on antigen‐specific
B
cells has not been reported following controlled human malaria infection (
CHMI
). Here we analysed human
B
‐cell responses in a series of
P
hase I/IIa clinical trials, which include
CHMI
, using candidate virus‐vectored vaccines encoding two blood‐stage antigens: merozoite surface protein 1 (
MSP
1) and apical membrane antigen 1 (
AMA
1). Previously vaccinated volunteers show boosting of pre‐existing antigen‐specific memory
B
‐cell (m
BC
) responses following
CHMI
. In contrast, unvaccinated malaria‐naive control volunteers developed an m
BC
response against
MSP
1 but not
AMA
1. Serum
I
g
G
correlated with the m
BC
response after booster vaccination but this relationship was less well maintained following
CHMI
. A significant reduction in peripheral
MSP
1‐specific m
BC
was observed at the point of diagnosis of blood‐stage infection. This was coincident with a reduction in peripheral blood
B
‐cell subsets expressing
CXCR
3 and elevated serum levels of interferon‐
γ
and
CXCL
9, suggesting migration away from the periphery. These
CHMI
data confirm that m
BC
and antibody responses can be induced and boosted by blood‐stage parasite exposure, in support of epidemiological studies on low‐level parasite exposure.</description><issn>0019-2805</issn><issn>1365-2567</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNotUMtKA0EQHETBGD34B331sHEeO7Ob4xo0CgkKBq9LZx5mZHcm7CRIPIif4Df6JW6ifanupqooipBLRkesn2vftiPGOVdHZMCEkhmXqjgmA0rZOOMllafkLKW3_hRUygH5rAI2u-QTRAerbYsBbuDn61vbpoHOpnUMySZwsWniuw-vMIEVVGCU6Ekwf6lg_vwEDDAYqOZVv_UJtsF_4MbHcHjrGDZdr7cGWmyw8wg-OKv3hHNy4rBJ9uIfh2Rxd7uY3Gezx-nDpJplushVxgqtraGWykJxQY0z49zQ3Jp8yUttC6aQIVfSUIrClViiXbo850qJZS7GTgzJ1Z-t7mJKnXX1uvMtdrua0XrfW92nrg-9iV-46WGN</recordid><startdate>201404</startdate><enddate>201404</enddate><creator>Elias, Sean C.</creator><creator>Choudhary, Prateek</creator><creator>de Cassan, Simone C.</creator><creator>Biswas, Sumi</creator><creator>Collins, Katharine A.</creator><creator>Halstead, Fenella D.</creator><creator>Bliss, Carly M.</creator><creator>Ewer, Katie J.</creator><creator>Hodgson, Susanne H.</creator><creator>Duncan, Christopher J. A.</creator><creator>Hill, Adrian V. S.</creator><creator>Draper, Simon J.</creator><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>201404</creationdate><title>Analysis of human B ‐cell responses following C h A d63‐ MVA MSP 1 and AMA 1 immunization and controlled malaria infection</title><author>Elias, Sean C. ; Choudhary, Prateek ; de Cassan, Simone C. ; Biswas, Sumi ; Collins, Katharine A. ; Halstead, Fenella D. ; Bliss, Carly M. ; Ewer, Katie J. ; Hodgson, Susanne H. ; Duncan, Christopher J. A. ; Hill, Adrian V. S. ; Draper, Simon J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c746-17cced0e0576230dfd94d04ed4b28ce716a1a265d00a3f8a8aebf442663b439f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Elias, Sean C.</creatorcontrib><creatorcontrib>Choudhary, Prateek</creatorcontrib><creatorcontrib>de Cassan, Simone C.</creatorcontrib><creatorcontrib>Biswas, Sumi</creatorcontrib><creatorcontrib>Collins, Katharine A.</creatorcontrib><creatorcontrib>Halstead, Fenella D.</creatorcontrib><creatorcontrib>Bliss, Carly M.</creatorcontrib><creatorcontrib>Ewer, Katie J.</creatorcontrib><creatorcontrib>Hodgson, Susanne H.</creatorcontrib><creatorcontrib>Duncan, Christopher J. A.</creatorcontrib><creatorcontrib>Hill, Adrian V. S.</creatorcontrib><creatorcontrib>Draper, Simon J.</creatorcontrib><collection>CrossRef</collection><jtitle>Immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Elias, Sean C.</au><au>Choudhary, Prateek</au><au>de Cassan, Simone C.</au><au>Biswas, Sumi</au><au>Collins, Katharine A.</au><au>Halstead, Fenella D.</au><au>Bliss, Carly M.</au><au>Ewer, Katie J.</au><au>Hodgson, Susanne H.</au><au>Duncan, Christopher J. A.</au><au>Hill, Adrian V. S.</au><au>Draper, Simon J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analysis of human B ‐cell responses following C h A d63‐ MVA MSP 1 and AMA 1 immunization and controlled malaria infection</atitle><jtitle>Immunology</jtitle><date>2014-04</date><risdate>2014</risdate><volume>141</volume><issue>4</issue><spage>628</spage><epage>644</epage><pages>628-644</pages><issn>0019-2805</issn><eissn>1365-2567</eissn><abstract>Acquisition of non‐sterilizing natural immunity to
P
lasmodium falciparum
malaria has been shown in low transmission areas following multiple exposures. However, conflicting data from endemic areas suggest that the parasite may interfere with the induction of effective
B
‐cell responses. To date, the impact of blood‐stage parasite exposure on antigen‐specific
B
cells has not been reported following controlled human malaria infection (
CHMI
). Here we analysed human
B
‐cell responses in a series of
P
hase I/IIa clinical trials, which include
CHMI
, using candidate virus‐vectored vaccines encoding two blood‐stage antigens: merozoite surface protein 1 (
MSP
1) and apical membrane antigen 1 (
AMA
1). Previously vaccinated volunteers show boosting of pre‐existing antigen‐specific memory
B
‐cell (m
BC
) responses following
CHMI
. In contrast, unvaccinated malaria‐naive control volunteers developed an m
BC
response against
MSP
1 but not
AMA
1. Serum
I
g
G
correlated with the m
BC
response after booster vaccination but this relationship was less well maintained following
CHMI
. A significant reduction in peripheral
MSP
1‐specific m
BC
was observed at the point of diagnosis of blood‐stage infection. This was coincident with a reduction in peripheral blood
B
‐cell subsets expressing
CXCR
3 and elevated serum levels of interferon‐
γ
and
CXCL
9, suggesting migration away from the periphery. These
CHMI
data confirm that m
BC
and antibody responses can be induced and boosted by blood‐stage parasite exposure, in support of epidemiological studies on low‐level parasite exposure.</abstract><doi>10.1111/imm.12226</doi><tpages>17</tpages></addata></record> |
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title | Analysis of human B ‐cell responses following C h A d63‐ MVA MSP 1 and AMA 1 immunization and controlled malaria infection |
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