IMRAS-Immunization with radiation-attenuated Plasmodium falciparum sporozoites by mosquito bite: Cellular immunity to sporozoites, CSP, AMA1, TRAP and CelTOS.

<h4<Background</h4<Immunization with radiation-attenuated sporozoites (RAS) by mosquito bites provides <90% sterile protection against Plasmodium falciparum malaria in humans. We conducted a clinical trial based on data from previous RAS clinical trials that suggested that 800-1200 infected bites should induce ~50% protective vaccine efficacy (VE) against controlled human malaria infection (CHMI) administered three weeks after the final immunization. Two cohorts were immunized separately. VE was 55% in Cohort 1 but 90% in Cohort 2, the cohort that received a higher first dose and a reduced (fractional) fifth dose. Immune responses were better boosted by the fractional fifth dose in Cohort 2 and suggested the importance of the fractional fifth dose for increased protection in Cohort 2 responses. Three protected subjects were later boosted and were protected suggesting that protection could be extended to at least 67 weeks.<h4<Methods</h4<The ex vivo FluoroSpot assay was used to measure peripheral IFN-γ, IL2, and IFN-γ+IL2 responses to PfNF54 sporozoites and malaria antigens CSP, AMA1, TRAP, and CelTOS using pools of synthetic overlapping 15mer peptides spanning each antigen.<h4<Results</h4<There was no correlation between IFN-γ, IL2, and IFN-γ+IL2 responses to sporozoites and protection, but fold-increases between post-4th and post-5th responses greater than 1.0 occurred mostly in protected subjects. IFN-γ and IL2 responses to TRAP, CelTOS and CSP occurred only in protected subjects. Peripheral IFN-γ, IL2, and IFN-γ+IL2 responses were short-lived and low by 27 weeks post-CHMI but were restored by boosting.<h4<Conclusions</h4<These studies highlight the importance of vaccine dose and schedule for vaccine efficacy, and suggest that CSP, TRAP, AMA1 and CelTOS may be targets of protective immunity. The correlation between fold-increases in responses and protection should be explored in other vaccine trials.<h4<Trial registration</h4<ClinicalTrials.gov NCT01994525. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Martha Sedegah [verfasserIn] Michael R Hollingdale [verfasserIn] Harini Ganeshan [verfasserIn] Maria Belmonte [verfasserIn] Jun Huang [verfasserIn] Arnel Belmonte [verfasserIn] Sandra Inoue [verfasserIn] Rachel Velasco [verfasserIn] Bradley Hickey [verfasserIn] Nimfa Teneza-Mora [verfasserIn] Joanne Lumsden [verfasserIn] Sharina Reyes [verfasserIn] Jo Glenna Banania [verfasserIn] Anatalio Reyes [verfasserIn] Ivelese Guzman [verfasserIn] Thomas L Richie [verfasserIn] Judith E Epstein [verfasserIn] Eileen Villasante [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Übergeordnetes Werk:	In: PLoS ONE - Public Library of Science (PLoS), 2007, 16(2021), 8, p e0256396
Übergeordnetes Werk:	volume:16 ; year:2021 ; number:8, p e0256396

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1371/journal.pone.0256396

Katalog-ID:	DOAJ049317431

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520			\|a <h4<Background</h4<Immunization with radiation-attenuated sporozoites (RAS) by mosquito bites provides <90% sterile protection against Plasmodium falciparum malaria in humans. We conducted a clinical trial based on data from previous RAS clinical trials that suggested that 800-1200 infected bites should induce ~50% protective vaccine efficacy (VE) against controlled human malaria infection (CHMI) administered three weeks after the final immunization. Two cohorts were immunized separately. VE was 55% in Cohort 1 but 90% in Cohort 2, the cohort that received a higher first dose and a reduced (fractional) fifth dose. Immune responses were better boosted by the fractional fifth dose in Cohort 2 and suggested the importance of the fractional fifth dose for increased protection in Cohort 2 responses. Three protected subjects were later boosted and were protected suggesting that protection could be extended to at least 67 weeks.<h4<Methods</h4<The ex vivo FluoroSpot assay was used to measure peripheral IFN-γ, IL2, and IFN-γ+IL2 responses to PfNF54 sporozoites and malaria antigens CSP, AMA1, TRAP, and CelTOS using pools of synthetic overlapping 15mer peptides spanning each antigen.<h4<Results</h4<There was no correlation between IFN-γ, IL2, and IFN-γ+IL2 responses to sporozoites and protection, but fold-increases between post-4th and post-5th responses greater than 1.0 occurred mostly in protected subjects. IFN-γ and IL2 responses to TRAP, CelTOS and CSP occurred only in protected subjects. Peripheral IFN-γ, IL2, and IFN-γ+IL2 responses were short-lived and low by 27 weeks post-CHMI but were restored by boosting.<h4<Conclusions</h4<These studies highlight the importance of vaccine dose and schedule for vaccine efficacy, and suggest that CSP, TRAP, AMA1 and CelTOS may be targets of protective immunity. The correlation between fold-increases in responses and protection should be explored in other vaccine trials.<h4<Trial registration</h4<ClinicalTrials.gov NCT01994525.
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700	0		\|a Ivelese Guzman \|e verfasserin \|4 aut
700	0		\|a Thomas L Richie \|e verfasserin \|4 aut
700	0		\|a Judith E Epstein \|e verfasserin \|4 aut
700	0		\|a Eileen Villasante \|e verfasserin \|4 aut
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allfields	10.1371/journal.pone.0256396 doi (DE-627)DOAJ049317431 (DE-599)DOAJ976cc23ed31b4e119cfee358be5ef4ee DE-627 ger DE-627 rakwb eng Martha Sedegah verfasserin aut IMRAS-Immunization with radiation-attenuated Plasmodium falciparum sporozoites by mosquito bite: Cellular immunity to sporozoites, CSP, AMA1, TRAP and CelTOS. 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4<Immunization with radiation-attenuated sporozoites (RAS) by mosquito bites provides <90% sterile protection against Plasmodium falciparum malaria in humans. We conducted a clinical trial based on data from previous RAS clinical trials that suggested that 800-1200 infected bites should induce ~50% protective vaccine efficacy (VE) against controlled human malaria infection (CHMI) administered three weeks after the final immunization. Two cohorts were immunized separately. VE was 55% in Cohort 1 but 90% in Cohort 2, the cohort that received a higher first dose and a reduced (fractional) fifth dose. Immune responses were better boosted by the fractional fifth dose in Cohort 2 and suggested the importance of the fractional fifth dose for increased protection in Cohort 2 responses. Three protected subjects were later boosted and were protected suggesting that protection could be extended to at least 67 weeks.<h4<Methods</h4<The ex vivo FluoroSpot assay was used to measure peripheral IFN-γ, IL2, and IFN-γ+IL2 responses to PfNF54 sporozoites and malaria antigens CSP, AMA1, TRAP, and CelTOS using pools of synthetic overlapping 15mer peptides spanning each antigen.<h4<Results</h4<There was no correlation between IFN-γ, IL2, and IFN-γ+IL2 responses to sporozoites and protection, but fold-increases between post-4th and post-5th responses greater than 1.0 occurred mostly in protected subjects. IFN-γ and IL2 responses to TRAP, CelTOS and CSP occurred only in protected subjects. Peripheral IFN-γ, IL2, and IFN-γ+IL2 responses were short-lived and low by 27 weeks post-CHMI but were restored by boosting.<h4<Conclusions</h4<These studies highlight the importance of vaccine dose and schedule for vaccine efficacy, and suggest that CSP, TRAP, AMA1 and CelTOS may be targets of protective immunity. The correlation between fold-increases in responses and protection should be explored in other vaccine trials.<h4<Trial registration</h4<ClinicalTrials.gov NCT01994525. Medicine R Science Q Michael R Hollingdale verfasserin aut Harini Ganeshan verfasserin aut Maria Belmonte verfasserin aut Jun Huang verfasserin aut Arnel Belmonte verfasserin aut Sandra Inoue verfasserin aut Rachel Velasco verfasserin aut Bradley Hickey verfasserin aut Nimfa Teneza-Mora verfasserin aut Joanne Lumsden verfasserin aut Sharina Reyes verfasserin aut Jo Glenna Banania verfasserin aut Anatalio Reyes verfasserin aut Ivelese Guzman verfasserin aut Thomas L Richie verfasserin aut Judith E Epstein verfasserin aut Eileen Villasante verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 16(2021), 8, p e0256396 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:16 year:2021 number:8, p e0256396 https://doi.org/10.1371/journal.pone.0256396 kostenfrei https://doaj.org/article/976cc23ed31b4e119cfee358be5ef4ee kostenfrei https://doi.org/10.1371/journal.pone.0256396 kostenfrei https://doaj.org/toc/1932-6203 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_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2021 8, p e0256396
spelling	10.1371/journal.pone.0256396 doi (DE-627)DOAJ049317431 (DE-599)DOAJ976cc23ed31b4e119cfee358be5ef4ee DE-627 ger DE-627 rakwb eng Martha Sedegah verfasserin aut IMRAS-Immunization with radiation-attenuated Plasmodium falciparum sporozoites by mosquito bite: Cellular immunity to sporozoites, CSP, AMA1, TRAP and CelTOS. 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4<Immunization with radiation-attenuated sporozoites (RAS) by mosquito bites provides <90% sterile protection against Plasmodium falciparum malaria in humans. We conducted a clinical trial based on data from previous RAS clinical trials that suggested that 800-1200 infected bites should induce ~50% protective vaccine efficacy (VE) against controlled human malaria infection (CHMI) administered three weeks after the final immunization. Two cohorts were immunized separately. VE was 55% in Cohort 1 but 90% in Cohort 2, the cohort that received a higher first dose and a reduced (fractional) fifth dose. Immune responses were better boosted by the fractional fifth dose in Cohort 2 and suggested the importance of the fractional fifth dose for increased protection in Cohort 2 responses. Three protected subjects were later boosted and were protected suggesting that protection could be extended to at least 67 weeks.<h4<Methods</h4<The ex vivo FluoroSpot assay was used to measure peripheral IFN-γ, IL2, and IFN-γ+IL2 responses to PfNF54 sporozoites and malaria antigens CSP, AMA1, TRAP, and CelTOS using pools of synthetic overlapping 15mer peptides spanning each antigen.<h4<Results</h4<There was no correlation between IFN-γ, IL2, and IFN-γ+IL2 responses to sporozoites and protection, but fold-increases between post-4th and post-5th responses greater than 1.0 occurred mostly in protected subjects. IFN-γ and IL2 responses to TRAP, CelTOS and CSP occurred only in protected subjects. Peripheral IFN-γ, IL2, and IFN-γ+IL2 responses were short-lived and low by 27 weeks post-CHMI but were restored by boosting.<h4<Conclusions</h4<These studies highlight the importance of vaccine dose and schedule for vaccine efficacy, and suggest that CSP, TRAP, AMA1 and CelTOS may be targets of protective immunity. The correlation between fold-increases in responses and protection should be explored in other vaccine trials.<h4<Trial registration</h4<ClinicalTrials.gov NCT01994525. Medicine R Science Q Michael R Hollingdale verfasserin aut Harini Ganeshan verfasserin aut Maria Belmonte verfasserin aut Jun Huang verfasserin aut Arnel Belmonte verfasserin aut Sandra Inoue verfasserin aut Rachel Velasco verfasserin aut Bradley Hickey verfasserin aut Nimfa Teneza-Mora verfasserin aut Joanne Lumsden verfasserin aut Sharina Reyes verfasserin aut Jo Glenna Banania verfasserin aut Anatalio Reyes verfasserin aut Ivelese Guzman verfasserin aut Thomas L Richie verfasserin aut Judith E Epstein verfasserin aut Eileen Villasante verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 16(2021), 8, p e0256396 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:16 year:2021 number:8, p e0256396 https://doi.org/10.1371/journal.pone.0256396 kostenfrei https://doaj.org/article/976cc23ed31b4e119cfee358be5ef4ee kostenfrei https://doi.org/10.1371/journal.pone.0256396 kostenfrei https://doaj.org/toc/1932-6203 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_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2021 8, p e0256396
allfields_unstemmed	10.1371/journal.pone.0256396 doi (DE-627)DOAJ049317431 (DE-599)DOAJ976cc23ed31b4e119cfee358be5ef4ee DE-627 ger DE-627 rakwb eng Martha Sedegah verfasserin aut IMRAS-Immunization with radiation-attenuated Plasmodium falciparum sporozoites by mosquito bite: Cellular immunity to sporozoites, CSP, AMA1, TRAP and CelTOS. 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4<Immunization with radiation-attenuated sporozoites (RAS) by mosquito bites provides <90% sterile protection against Plasmodium falciparum malaria in humans. We conducted a clinical trial based on data from previous RAS clinical trials that suggested that 800-1200 infected bites should induce ~50% protective vaccine efficacy (VE) against controlled human malaria infection (CHMI) administered three weeks after the final immunization. Two cohorts were immunized separately. VE was 55% in Cohort 1 but 90% in Cohort 2, the cohort that received a higher first dose and a reduced (fractional) fifth dose. Immune responses were better boosted by the fractional fifth dose in Cohort 2 and suggested the importance of the fractional fifth dose for increased protection in Cohort 2 responses. Three protected subjects were later boosted and were protected suggesting that protection could be extended to at least 67 weeks.<h4<Methods</h4<The ex vivo FluoroSpot assay was used to measure peripheral IFN-γ, IL2, and IFN-γ+IL2 responses to PfNF54 sporozoites and malaria antigens CSP, AMA1, TRAP, and CelTOS using pools of synthetic overlapping 15mer peptides spanning each antigen.<h4<Results</h4<There was no correlation between IFN-γ, IL2, and IFN-γ+IL2 responses to sporozoites and protection, but fold-increases between post-4th and post-5th responses greater than 1.0 occurred mostly in protected subjects. IFN-γ and IL2 responses to TRAP, CelTOS and CSP occurred only in protected subjects. Peripheral IFN-γ, IL2, and IFN-γ+IL2 responses were short-lived and low by 27 weeks post-CHMI but were restored by boosting.<h4<Conclusions</h4<These studies highlight the importance of vaccine dose and schedule for vaccine efficacy, and suggest that CSP, TRAP, AMA1 and CelTOS may be targets of protective immunity. The correlation between fold-increases in responses and protection should be explored in other vaccine trials.<h4<Trial registration</h4<ClinicalTrials.gov NCT01994525. Medicine R Science Q Michael R Hollingdale verfasserin aut Harini Ganeshan verfasserin aut Maria Belmonte verfasserin aut Jun Huang verfasserin aut Arnel Belmonte verfasserin aut Sandra Inoue verfasserin aut Rachel Velasco verfasserin aut Bradley Hickey verfasserin aut Nimfa Teneza-Mora verfasserin aut Joanne Lumsden verfasserin aut Sharina Reyes verfasserin aut Jo Glenna Banania verfasserin aut Anatalio Reyes verfasserin aut Ivelese Guzman verfasserin aut Thomas L Richie verfasserin aut Judith E Epstein verfasserin aut Eileen Villasante verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 16(2021), 8, p e0256396 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:16 year:2021 number:8, p e0256396 https://doi.org/10.1371/journal.pone.0256396 kostenfrei https://doaj.org/article/976cc23ed31b4e119cfee358be5ef4ee kostenfrei https://doi.org/10.1371/journal.pone.0256396 kostenfrei https://doaj.org/toc/1932-6203 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_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2021 8, p e0256396
allfieldsGer	10.1371/journal.pone.0256396 doi (DE-627)DOAJ049317431 (DE-599)DOAJ976cc23ed31b4e119cfee358be5ef4ee DE-627 ger DE-627 rakwb eng Martha Sedegah verfasserin aut IMRAS-Immunization with radiation-attenuated Plasmodium falciparum sporozoites by mosquito bite: Cellular immunity to sporozoites, CSP, AMA1, TRAP and CelTOS. 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4<Immunization with radiation-attenuated sporozoites (RAS) by mosquito bites provides <90% sterile protection against Plasmodium falciparum malaria in humans. We conducted a clinical trial based on data from previous RAS clinical trials that suggested that 800-1200 infected bites should induce ~50% protective vaccine efficacy (VE) against controlled human malaria infection (CHMI) administered three weeks after the final immunization. Two cohorts were immunized separately. VE was 55% in Cohort 1 but 90% in Cohort 2, the cohort that received a higher first dose and a reduced (fractional) fifth dose. Immune responses were better boosted by the fractional fifth dose in Cohort 2 and suggested the importance of the fractional fifth dose for increased protection in Cohort 2 responses. Three protected subjects were later boosted and were protected suggesting that protection could be extended to at least 67 weeks.<h4<Methods</h4<The ex vivo FluoroSpot assay was used to measure peripheral IFN-γ, IL2, and IFN-γ+IL2 responses to PfNF54 sporozoites and malaria antigens CSP, AMA1, TRAP, and CelTOS using pools of synthetic overlapping 15mer peptides spanning each antigen.<h4<Results</h4<There was no correlation between IFN-γ, IL2, and IFN-γ+IL2 responses to sporozoites and protection, but fold-increases between post-4th and post-5th responses greater than 1.0 occurred mostly in protected subjects. IFN-γ and IL2 responses to TRAP, CelTOS and CSP occurred only in protected subjects. Peripheral IFN-γ, IL2, and IFN-γ+IL2 responses were short-lived and low by 27 weeks post-CHMI but were restored by boosting.<h4<Conclusions</h4<These studies highlight the importance of vaccine dose and schedule for vaccine efficacy, and suggest that CSP, TRAP, AMA1 and CelTOS may be targets of protective immunity. The correlation between fold-increases in responses and protection should be explored in other vaccine trials.<h4<Trial registration</h4<ClinicalTrials.gov NCT01994525. Medicine R Science Q Michael R Hollingdale verfasserin aut Harini Ganeshan verfasserin aut Maria Belmonte verfasserin aut Jun Huang verfasserin aut Arnel Belmonte verfasserin aut Sandra Inoue verfasserin aut Rachel Velasco verfasserin aut Bradley Hickey verfasserin aut Nimfa Teneza-Mora verfasserin aut Joanne Lumsden verfasserin aut Sharina Reyes verfasserin aut Jo Glenna Banania verfasserin aut Anatalio Reyes verfasserin aut Ivelese Guzman verfasserin aut Thomas L Richie verfasserin aut Judith E Epstein verfasserin aut Eileen Villasante verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 16(2021), 8, p e0256396 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:16 year:2021 number:8, p e0256396 https://doi.org/10.1371/journal.pone.0256396 kostenfrei https://doaj.org/article/976cc23ed31b4e119cfee358be5ef4ee kostenfrei https://doi.org/10.1371/journal.pone.0256396 kostenfrei https://doaj.org/toc/1932-6203 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_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2021 8, p e0256396
allfieldsSound	10.1371/journal.pone.0256396 doi (DE-627)DOAJ049317431 (DE-599)DOAJ976cc23ed31b4e119cfee358be5ef4ee DE-627 ger DE-627 rakwb eng Martha Sedegah verfasserin aut IMRAS-Immunization with radiation-attenuated Plasmodium falciparum sporozoites by mosquito bite: Cellular immunity to sporozoites, CSP, AMA1, TRAP and CelTOS. 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4<Immunization with radiation-attenuated sporozoites (RAS) by mosquito bites provides <90% sterile protection against Plasmodium falciparum malaria in humans. We conducted a clinical trial based on data from previous RAS clinical trials that suggested that 800-1200 infected bites should induce ~50% protective vaccine efficacy (VE) against controlled human malaria infection (CHMI) administered three weeks after the final immunization. Two cohorts were immunized separately. VE was 55% in Cohort 1 but 90% in Cohort 2, the cohort that received a higher first dose and a reduced (fractional) fifth dose. Immune responses were better boosted by the fractional fifth dose in Cohort 2 and suggested the importance of the fractional fifth dose for increased protection in Cohort 2 responses. Three protected subjects were later boosted and were protected suggesting that protection could be extended to at least 67 weeks.<h4<Methods</h4<The ex vivo FluoroSpot assay was used to measure peripheral IFN-γ, IL2, and IFN-γ+IL2 responses to PfNF54 sporozoites and malaria antigens CSP, AMA1, TRAP, and CelTOS using pools of synthetic overlapping 15mer peptides spanning each antigen.<h4<Results</h4<There was no correlation between IFN-γ, IL2, and IFN-γ+IL2 responses to sporozoites and protection, but fold-increases between post-4th and post-5th responses greater than 1.0 occurred mostly in protected subjects. IFN-γ and IL2 responses to TRAP, CelTOS and CSP occurred only in protected subjects. Peripheral IFN-γ, IL2, and IFN-γ+IL2 responses were short-lived and low by 27 weeks post-CHMI but were restored by boosting.<h4<Conclusions</h4<These studies highlight the importance of vaccine dose and schedule for vaccine efficacy, and suggest that CSP, TRAP, AMA1 and CelTOS may be targets of protective immunity. The correlation between fold-increases in responses and protection should be explored in other vaccine trials.<h4<Trial registration</h4<ClinicalTrials.gov NCT01994525. Medicine R Science Q Michael R Hollingdale verfasserin aut Harini Ganeshan verfasserin aut Maria Belmonte verfasserin aut Jun Huang verfasserin aut Arnel Belmonte verfasserin aut Sandra Inoue verfasserin aut Rachel Velasco verfasserin aut Bradley Hickey verfasserin aut Nimfa Teneza-Mora verfasserin aut Joanne Lumsden verfasserin aut Sharina Reyes verfasserin aut Jo Glenna Banania verfasserin aut Anatalio Reyes verfasserin aut Ivelese Guzman verfasserin aut Thomas L Richie verfasserin aut Judith E Epstein verfasserin aut Eileen Villasante verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 16(2021), 8, p e0256396 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:16 year:2021 number:8, p e0256396 https://doi.org/10.1371/journal.pone.0256396 kostenfrei https://doaj.org/article/976cc23ed31b4e119cfee358be5ef4ee kostenfrei https://doi.org/10.1371/journal.pone.0256396 kostenfrei https://doaj.org/toc/1932-6203 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_34 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_235 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 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_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 16 2021 8, p e0256396
language	English
source	In PLoS ONE 16(2021), 8, p e0256396 volume:16 year:2021 number:8, p e0256396
sourceStr	In PLoS ONE 16(2021), 8, p e0256396 volume:16 year:2021 number:8, p e0256396
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Medicine R Science Q
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container_title	PLoS ONE
authorswithroles_txt_mv	Martha Sedegah @@aut@@ Michael R Hollingdale @@aut@@ Harini Ganeshan @@aut@@ Maria Belmonte @@aut@@ Jun Huang @@aut@@ Arnel Belmonte @@aut@@ Sandra Inoue @@aut@@ Rachel Velasco @@aut@@ Bradley Hickey @@aut@@ Nimfa Teneza-Mora @@aut@@ Joanne Lumsden @@aut@@ Sharina Reyes @@aut@@ Jo Glenna Banania @@aut@@ Anatalio Reyes @@aut@@ Ivelese Guzman @@aut@@ Thomas L Richie @@aut@@ Judith E Epstein @@aut@@ Eileen Villasante @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
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We conducted a clinical trial based on data from previous RAS clinical trials that suggested that 800-1200 infected bites should induce ~50% protective vaccine efficacy (VE) against controlled human malaria infection (CHMI) administered three weeks after the final immunization. Two cohorts were immunized separately. VE was 55% in Cohort 1 but 90% in Cohort 2, the cohort that received a higher first dose and a reduced (fractional) fifth dose. Immune responses were better boosted by the fractional fifth dose in Cohort 2 and suggested the importance of the fractional fifth dose for increased protection in Cohort 2 responses. Three protected subjects were later boosted and were protected suggesting that protection could be extended to at least 67 weeks.<h4<Methods</h4<The ex vivo FluoroSpot assay was used to measure peripheral IFN-γ, IL2, and IFN-γ+IL2 responses to PfNF54 sporozoites and malaria antigens CSP, AMA1, TRAP, and CelTOS using pools of synthetic overlapping 15mer peptides spanning each antigen.<h4<Results</h4<There was no correlation between IFN-γ, IL2, and IFN-γ+IL2 responses to sporozoites and protection, but fold-increases between post-4th and post-5th responses greater than 1.0 occurred mostly in protected subjects. IFN-γ and IL2 responses to TRAP, CelTOS and CSP occurred only in protected subjects. 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author	Martha Sedegah
spellingShingle	Martha Sedegah misc Medicine misc R misc Science misc Q IMRAS-Immunization with radiation-attenuated Plasmodium falciparum sporozoites by mosquito bite: Cellular immunity to sporozoites, CSP, AMA1, TRAP and CelTOS.
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topic_title	IMRAS-Immunization with radiation-attenuated Plasmodium falciparum sporozoites by mosquito bite: Cellular immunity to sporozoites, CSP, AMA1, TRAP and CelTOS
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title	IMRAS-Immunization with radiation-attenuated Plasmodium falciparum sporozoites by mosquito bite: Cellular immunity to sporozoites, CSP, AMA1, TRAP and CelTOS.
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title_full	IMRAS-Immunization with radiation-attenuated Plasmodium falciparum sporozoites by mosquito bite: Cellular immunity to sporozoites, CSP, AMA1, TRAP and CelTOS
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author_browse	Martha Sedegah Michael R Hollingdale Harini Ganeshan Maria Belmonte Jun Huang Arnel Belmonte Sandra Inoue Rachel Velasco Bradley Hickey Nimfa Teneza-Mora Joanne Lumsden Sharina Reyes Jo Glenna Banania Anatalio Reyes Ivelese Guzman Thomas L Richie Judith E Epstein Eileen Villasante
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title_sort	imras-immunization with radiation-attenuated plasmodium falciparum sporozoites by mosquito bite: cellular immunity to sporozoites, csp, ama1, trap and celtos
title_auth	IMRAS-Immunization with radiation-attenuated Plasmodium falciparum sporozoites by mosquito bite: Cellular immunity to sporozoites, CSP, AMA1, TRAP and CelTOS.
abstract	<h4<Background</h4<Immunization with radiation-attenuated sporozoites (RAS) by mosquito bites provides <90% sterile protection against Plasmodium falciparum malaria in humans. We conducted a clinical trial based on data from previous RAS clinical trials that suggested that 800-1200 infected bites should induce ~50% protective vaccine efficacy (VE) against controlled human malaria infection (CHMI) administered three weeks after the final immunization. Two cohorts were immunized separately. VE was 55% in Cohort 1 but 90% in Cohort 2, the cohort that received a higher first dose and a reduced (fractional) fifth dose. Immune responses were better boosted by the fractional fifth dose in Cohort 2 and suggested the importance of the fractional fifth dose for increased protection in Cohort 2 responses. Three protected subjects were later boosted and were protected suggesting that protection could be extended to at least 67 weeks.<h4<Methods</h4<The ex vivo FluoroSpot assay was used to measure peripheral IFN-γ, IL2, and IFN-γ+IL2 responses to PfNF54 sporozoites and malaria antigens CSP, AMA1, TRAP, and CelTOS using pools of synthetic overlapping 15mer peptides spanning each antigen.<h4<Results</h4<There was no correlation between IFN-γ, IL2, and IFN-γ+IL2 responses to sporozoites and protection, but fold-increases between post-4th and post-5th responses greater than 1.0 occurred mostly in protected subjects. IFN-γ and IL2 responses to TRAP, CelTOS and CSP occurred only in protected subjects. Peripheral IFN-γ, IL2, and IFN-γ+IL2 responses were short-lived and low by 27 weeks post-CHMI but were restored by boosting.<h4<Conclusions</h4<These studies highlight the importance of vaccine dose and schedule for vaccine efficacy, and suggest that CSP, TRAP, AMA1 and CelTOS may be targets of protective immunity. The correlation between fold-increases in responses and protection should be explored in other vaccine trials.<h4<Trial registration</h4<ClinicalTrials.gov NCT01994525.
abstractGer	<h4<Background</h4<Immunization with radiation-attenuated sporozoites (RAS) by mosquito bites provides <90% sterile protection against Plasmodium falciparum malaria in humans. We conducted a clinical trial based on data from previous RAS clinical trials that suggested that 800-1200 infected bites should induce ~50% protective vaccine efficacy (VE) against controlled human malaria infection (CHMI) administered three weeks after the final immunization. Two cohorts were immunized separately. VE was 55% in Cohort 1 but 90% in Cohort 2, the cohort that received a higher first dose and a reduced (fractional) fifth dose. Immune responses were better boosted by the fractional fifth dose in Cohort 2 and suggested the importance of the fractional fifth dose for increased protection in Cohort 2 responses. Three protected subjects were later boosted and were protected suggesting that protection could be extended to at least 67 weeks.<h4<Methods</h4<The ex vivo FluoroSpot assay was used to measure peripheral IFN-γ, IL2, and IFN-γ+IL2 responses to PfNF54 sporozoites and malaria antigens CSP, AMA1, TRAP, and CelTOS using pools of synthetic overlapping 15mer peptides spanning each antigen.<h4<Results</h4<There was no correlation between IFN-γ, IL2, and IFN-γ+IL2 responses to sporozoites and protection, but fold-increases between post-4th and post-5th responses greater than 1.0 occurred mostly in protected subjects. IFN-γ and IL2 responses to TRAP, CelTOS and CSP occurred only in protected subjects. Peripheral IFN-γ, IL2, and IFN-γ+IL2 responses were short-lived and low by 27 weeks post-CHMI but were restored by boosting.<h4<Conclusions</h4<These studies highlight the importance of vaccine dose and schedule for vaccine efficacy, and suggest that CSP, TRAP, AMA1 and CelTOS may be targets of protective immunity. The correlation between fold-increases in responses and protection should be explored in other vaccine trials.<h4<Trial registration</h4<ClinicalTrials.gov NCT01994525.
abstract_unstemmed	<h4<Background</h4<Immunization with radiation-attenuated sporozoites (RAS) by mosquito bites provides <90% sterile protection against Plasmodium falciparum malaria in humans. We conducted a clinical trial based on data from previous RAS clinical trials that suggested that 800-1200 infected bites should induce ~50% protective vaccine efficacy (VE) against controlled human malaria infection (CHMI) administered three weeks after the final immunization. Two cohorts were immunized separately. VE was 55% in Cohort 1 but 90% in Cohort 2, the cohort that received a higher first dose and a reduced (fractional) fifth dose. Immune responses were better boosted by the fractional fifth dose in Cohort 2 and suggested the importance of the fractional fifth dose for increased protection in Cohort 2 responses. Three protected subjects were later boosted and were protected suggesting that protection could be extended to at least 67 weeks.<h4<Methods</h4<The ex vivo FluoroSpot assay was used to measure peripheral IFN-γ, IL2, and IFN-γ+IL2 responses to PfNF54 sporozoites and malaria antigens CSP, AMA1, TRAP, and CelTOS using pools of synthetic overlapping 15mer peptides spanning each antigen.<h4<Results</h4<There was no correlation between IFN-γ, IL2, and IFN-γ+IL2 responses to sporozoites and protection, but fold-increases between post-4th and post-5th responses greater than 1.0 occurred mostly in protected subjects. IFN-γ and IL2 responses to TRAP, CelTOS and CSP occurred only in protected subjects. Peripheral IFN-γ, IL2, and IFN-γ+IL2 responses were short-lived and low by 27 weeks post-CHMI but were restored by boosting.<h4<Conclusions</h4<These studies highlight the importance of vaccine dose and schedule for vaccine efficacy, and suggest that CSP, TRAP, AMA1 and CelTOS may be targets of protective immunity. The correlation between fold-increases in responses and protection should be explored in other vaccine trials.<h4<Trial registration</h4<ClinicalTrials.gov NCT01994525.
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container_issue	8, p e0256396
title_short	IMRAS-Immunization with radiation-attenuated Plasmodium falciparum sporozoites by mosquito bite: Cellular immunity to sporozoites, CSP, AMA1, TRAP and CelTOS.
url	https://doi.org/10.1371/journal.pone.0256396 https://doaj.org/article/976cc23ed31b4e119cfee358be5ef4ee https://doaj.org/toc/1932-6203
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author2	Michael R Hollingdale Harini Ganeshan Maria Belmonte Jun Huang Arnel Belmonte Sandra Inoue Rachel Velasco Bradley Hickey Nimfa Teneza-Mora Joanne Lumsden Sharina Reyes Jo Glenna Banania Anatalio Reyes Ivelese Guzman Thomas L Richie Judith E Epstein Eileen Villasante
author2Str	Michael R Hollingdale Harini Ganeshan Maria Belmonte Jun Huang Arnel Belmonte Sandra Inoue Rachel Velasco Bradley Hickey Nimfa Teneza-Mora Joanne Lumsden Sharina Reyes Jo Glenna Banania Anatalio Reyes Ivelese Guzman Thomas L Richie Judith E Epstein Eileen Villasante
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doi_str	10.1371/journal.pone.0256396
up_date	2024-07-03T22:41:59.529Z
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