A three-antigen Plasmodium falciparum DNA prime-Adenovirus boost malaria vaccine regimen is superior to a two-antigen regimen and protects against controlled human malaria infection in healthy malaria-naïve adults.

<h4<Background</h4<A DNA-prime/human adenovirus serotype 5 (HuAd5) boost vaccine encoding Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) and Pf apical membrane antigen-1 (PfAMA1), elicited protection in 4/15 (27%) of subjects against controlled human malaria infection (CHMI) that was statistically associated with CD8+ T cell responses. Subjects with high level pre-existing immunity to HuAd5 were not protected, suggesting an adverse effect on vaccine efficacy (VE). We replaced HuAd5 with chimpanzee adenovirus 63 (ChAd63), and repeated the study, assessing both the two-antigen (CSP, AMA1 = CA) vaccine, and a novel three-antigen (CSP, AMA1, ME-TRAP = CAT) vaccine that included a third pre-erythrocytic stage antigen [malaria multiple epitopes (ME) fused to the Pf thrombospondin-related adhesive protein (TRAP)] to potentially enhance protection.<h4<Methodology</h4<This was an open label, randomized Phase 1 trial, assessing safety, tolerability, and VE against CHMI in healthy, malaria naïve adults. Forty subjects (20 each group) were to receive three monthly CA or CAT DNA priming immunizations, followed by corresponding ChAd63 boost four months later. Four weeks after the boost, immunized subjects and 12 infectivity controls underwent CHMI by mosquito bite using the Pf3D7 strain. VE was assessed by determining the differences in time to parasitemia as detected by thick blood smears up to 28-days post CHMI and utilizing the log rank test, and by calculating the risk ratio of each treatment group and subtracting from 1, with significance calculated by the Cochran-Mantel-Haenszel method.<h4<Results</h4<In both groups, systemic adverse events (AEs) were significantly higher after the ChAd63 boost than DNA immunizations. Eleven of 12 infectivity controls developed parasitemia (mean 11.7 days). In the CA group, 15 of 16 (93.8%) immunized subjects developed parasitemia (mean 12.0 days). In the CAT group, 11 of 16 (63.8%) immunized subjects developed parasitemia (mean 13.0 days), indicating significant protection by log rank test compared to infectivity controls (p = 0.0406) and the CA group (p = 0.0229). VE (1 minus the risk ratio) in the CAT group was 25% compared to -2% in the CA group. The CA and CAT vaccines induced robust humoral (ELISA antibodies against CSP, AMA1 and TRAP, and IFA responses against sporozoites and Pf3D7 blood stages), and cellular responses (IFN-γ FluoroSpot responses to CSP, AMA1 and TRAP) that were not associated with protection.<h4<Conclusions</h4<This study demonstrated that the ChAd63 CAT vaccine exhibited significant protective efficacy, and confirmed protection was afforded by adding a third antigen (T) to a two-antigen (CA) formulation to achieve increased VE. Although the ChAd63-CAT vaccine was associated with increased frequencies of systemic AEs compared to the CA vaccine and, historically, compared to the HuAd5 vectored malaria vaccine encoding CSP and AMA1, they were transient and associated with increased vector dosing. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Marvin J Sklar [verfasserIn] Santina Maiolatesi [verfasserIn] Noelle Patterson [verfasserIn] Martha Sedegah [verfasserIn] Keith Limbach [verfasserIn] Nimfa Teneza-Mora [verfasserIn] Ilin Chuang [verfasserIn] K Monique Hollis-Perry [verfasserIn] Jo Glenna Banania [verfasserIn] Ivelese Guzman [verfasserIn] Harini Ganeshan [verfasserIn] Sharina Reyes [verfasserIn] Michael R Hollingdale [verfasserIn] Mimi Wong [verfasserIn] Ashley Lindstrom [verfasserIn] Anatalio Reyes [verfasserIn] Yolanda Alcorta [verfasserIn] Lindsey Garver [verfasserIn] Kelli Bankard [verfasserIn] Arnel Belmonte [verfasserIn] Maria Belmonte [verfasserIn] Jun Huang [verfasserIn] Kalpana Gowda [verfasserIn] Sandra Inoue [verfasserIn] Rachel Velasco [verfasserIn] Elke Bergmann-Leitner [verfasserIn] Jack Hutter [verfasserIn] Tida Lee [verfasserIn] Nehkonti Adams [verfasserIn] Sidhartha Chaudhury [verfasserIn] Devin Hunt [verfasserIn] Cindy Tamminga [verfasserIn] Eleanor Berrie [verfasserIn] Duncan Bellamy [verfasserIn] Mustapha Bittaye [verfasserIn] Katie Ewer [verfasserIn] Carter Diggs [verfasserIn] Lorraine A Soisson [verfasserIn] Alison Lawrie [verfasserIn] Adrian Hill [verfasserIn] Thomas L Richie [verfasserIn] Eileen Villasante [verfasserIn] Judith E Epstein [verfasserIn] Christopher A Duplessis [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Übergeordnetes Werk:	In: PLoS ONE - Public Library of Science (PLoS), 2007, 16(2021), 9, p e0256980
Übergeordnetes Werk:	volume:16 ; year:2021 ; number:9, p e0256980

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1371/journal.pone.0256980

Katalog-ID:	DOAJ051303698

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100	0		\|a Marvin J Sklar \|e verfasserin \|4 aut
245	1	2	\|a A three-antigen Plasmodium falciparum DNA prime-Adenovirus boost malaria vaccine regimen is superior to a two-antigen regimen and protects against controlled human malaria infection in healthy malaria-naïve adults.
264		1	\|c 2021
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520			\|a <h4<Background</h4<A DNA-prime/human adenovirus serotype 5 (HuAd5) boost vaccine encoding Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) and Pf apical membrane antigen-1 (PfAMA1), elicited protection in 4/15 (27%) of subjects against controlled human malaria infection (CHMI) that was statistically associated with CD8+ T cell responses. Subjects with high level pre-existing immunity to HuAd5 were not protected, suggesting an adverse effect on vaccine efficacy (VE). We replaced HuAd5 with chimpanzee adenovirus 63 (ChAd63), and repeated the study, assessing both the two-antigen (CSP, AMA1 = CA) vaccine, and a novel three-antigen (CSP, AMA1, ME-TRAP = CAT) vaccine that included a third pre-erythrocytic stage antigen [malaria multiple epitopes (ME) fused to the Pf thrombospondin-related adhesive protein (TRAP)] to potentially enhance protection.<h4<Methodology</h4<This was an open label, randomized Phase 1 trial, assessing safety, tolerability, and VE against CHMI in healthy, malaria naïve adults. Forty subjects (20 each group) were to receive three monthly CA or CAT DNA priming immunizations, followed by corresponding ChAd63 boost four months later. Four weeks after the boost, immunized subjects and 12 infectivity controls underwent CHMI by mosquito bite using the Pf3D7 strain. VE was assessed by determining the differences in time to parasitemia as detected by thick blood smears up to 28-days post CHMI and utilizing the log rank test, and by calculating the risk ratio of each treatment group and subtracting from 1, with significance calculated by the Cochran-Mantel-Haenszel method.<h4<Results</h4<In both groups, systemic adverse events (AEs) were significantly higher after the ChAd63 boost than DNA immunizations. Eleven of 12 infectivity controls developed parasitemia (mean 11.7 days). In the CA group, 15 of 16 (93.8%) immunized subjects developed parasitemia (mean 12.0 days). In the CAT group, 11 of 16 (63.8%) immunized subjects developed parasitemia (mean 13.0 days), indicating significant protection by log rank test compared to infectivity controls (p = 0.0406) and the CA group (p = 0.0229). VE (1 minus the risk ratio) in the CAT group was 25% compared to -2% in the CA group. The CA and CAT vaccines induced robust humoral (ELISA antibodies against CSP, AMA1 and TRAP, and IFA responses against sporozoites and Pf3D7 blood stages), and cellular responses (IFN-γ FluoroSpot responses to CSP, AMA1 and TRAP) that were not associated with protection.<h4<Conclusions</h4<This study demonstrated that the ChAd63 CAT vaccine exhibited significant protective efficacy, and confirmed protection was afforded by adding a third antigen (T) to a two-antigen (CA) formulation to achieve increased VE. Although the ChAd63-CAT vaccine was associated with increased frequencies of systemic AEs compared to the CA vaccine and, historically, compared to the HuAd5 vectored malaria vaccine encoding CSP and AMA1, they were transient and associated with increased vector dosing.
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700	0		\|a Noelle Patterson \|e verfasserin \|4 aut
700	0		\|a Martha Sedegah \|e verfasserin \|4 aut
700	0		\|a Keith Limbach \|e verfasserin \|4 aut
700	0		\|a Nimfa Teneza-Mora \|e verfasserin \|4 aut
700	0		\|a Ilin Chuang \|e verfasserin \|4 aut
700	0		\|a K Monique Hollis-Perry \|e verfasserin \|4 aut
700	0		\|a Jo Glenna Banania \|e verfasserin \|4 aut
700	0		\|a Ivelese Guzman \|e verfasserin \|4 aut
700	0		\|a Harini Ganeshan \|e verfasserin \|4 aut
700	0		\|a Sharina Reyes \|e verfasserin \|4 aut
700	0		\|a Michael R Hollingdale \|e verfasserin \|4 aut
700	0		\|a Mimi Wong \|e verfasserin \|4 aut
700	0		\|a Ashley Lindstrom \|e verfasserin \|4 aut
700	0		\|a Anatalio Reyes \|e verfasserin \|4 aut
700	0		\|a Yolanda Alcorta \|e verfasserin \|4 aut
700	0		\|a Lindsey Garver \|e verfasserin \|4 aut
700	0		\|a Kelli Bankard \|e verfasserin \|4 aut
700	0		\|a Arnel Belmonte \|e verfasserin \|4 aut
700	0		\|a Maria Belmonte \|e verfasserin \|4 aut
700	0		\|a Jun Huang \|e verfasserin \|4 aut
700	0		\|a Kalpana Gowda \|e verfasserin \|4 aut
700	0		\|a Sandra Inoue \|e verfasserin \|4 aut
700	0		\|a Rachel Velasco \|e verfasserin \|4 aut
700	0		\|a Elke Bergmann-Leitner \|e verfasserin \|4 aut
700	0		\|a Jack Hutter \|e verfasserin \|4 aut
700	0		\|a Tida Lee \|e verfasserin \|4 aut
700	0		\|a Nehkonti Adams \|e verfasserin \|4 aut
700	0		\|a Sidhartha Chaudhury \|e verfasserin \|4 aut
700	0		\|a Devin Hunt \|e verfasserin \|4 aut
700	0		\|a Cindy Tamminga \|e verfasserin \|4 aut
700	0		\|a Eleanor Berrie \|e verfasserin \|4 aut
700	0		\|a Duncan Bellamy \|e verfasserin \|4 aut
700	0		\|a Mustapha Bittaye \|e verfasserin \|4 aut
700	0		\|a Katie Ewer \|e verfasserin \|4 aut
700	0		\|a Carter Diggs \|e verfasserin \|4 aut
700	0		\|a Lorraine A Soisson \|e verfasserin \|4 aut
700	0		\|a Alison Lawrie \|e verfasserin \|4 aut
700	0		\|a Adrian Hill \|e verfasserin \|4 aut
700	0		\|a Thomas L Richie \|e verfasserin \|4 aut
700	0		\|a Eileen Villasante \|e verfasserin \|4 aut
700	0		\|a Judith E Epstein \|e verfasserin \|4 aut
700	0		\|a Christopher A Duplessis \|e verfasserin \|4 aut
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allfields	10.1371/journal.pone.0256980 doi (DE-627)DOAJ051303698 (DE-599)DOAJ4dc547617946467c9611eaa99d4458b4 DE-627 ger DE-627 rakwb eng Marvin J Sklar verfasserin aut A three-antigen Plasmodium falciparum DNA prime-Adenovirus boost malaria vaccine regimen is superior to a two-antigen regimen and protects against controlled human malaria infection in healthy malaria-naïve adults. 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4<A DNA-prime/human adenovirus serotype 5 (HuAd5) boost vaccine encoding Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) and Pf apical membrane antigen-1 (PfAMA1), elicited protection in 4/15 (27%) of subjects against controlled human malaria infection (CHMI) that was statistically associated with CD8+ T cell responses. Subjects with high level pre-existing immunity to HuAd5 were not protected, suggesting an adverse effect on vaccine efficacy (VE). We replaced HuAd5 with chimpanzee adenovirus 63 (ChAd63), and repeated the study, assessing both the two-antigen (CSP, AMA1 = CA) vaccine, and a novel three-antigen (CSP, AMA1, ME-TRAP = CAT) vaccine that included a third pre-erythrocytic stage antigen [malaria multiple epitopes (ME) fused to the Pf thrombospondin-related adhesive protein (TRAP)] to potentially enhance protection.<h4<Methodology</h4<This was an open label, randomized Phase 1 trial, assessing safety, tolerability, and VE against CHMI in healthy, malaria naïve adults. Forty subjects (20 each group) were to receive three monthly CA or CAT DNA priming immunizations, followed by corresponding ChAd63 boost four months later. Four weeks after the boost, immunized subjects and 12 infectivity controls underwent CHMI by mosquito bite using the Pf3D7 strain. VE was assessed by determining the differences in time to parasitemia as detected by thick blood smears up to 28-days post CHMI and utilizing the log rank test, and by calculating the risk ratio of each treatment group and subtracting from 1, with significance calculated by the Cochran-Mantel-Haenszel method.<h4<Results</h4<In both groups, systemic adverse events (AEs) were significantly higher after the ChAd63 boost than DNA immunizations. Eleven of 12 infectivity controls developed parasitemia (mean 11.7 days). In the CA group, 15 of 16 (93.8%) immunized subjects developed parasitemia (mean 12.0 days). In the CAT group, 11 of 16 (63.8%) immunized subjects developed parasitemia (mean 13.0 days), indicating significant protection by log rank test compared to infectivity controls (p = 0.0406) and the CA group (p = 0.0229). VE (1 minus the risk ratio) in the CAT group was 25% compared to -2% in the CA group. The CA and CAT vaccines induced robust humoral (ELISA antibodies against CSP, AMA1 and TRAP, and IFA responses against sporozoites and Pf3D7 blood stages), and cellular responses (IFN-γ FluoroSpot responses to CSP, AMA1 and TRAP) that were not associated with protection.<h4<Conclusions</h4<This study demonstrated that the ChAd63 CAT vaccine exhibited significant protective efficacy, and confirmed protection was afforded by adding a third antigen (T) to a two-antigen (CA) formulation to achieve increased VE. Although the ChAd63-CAT vaccine was associated with increased frequencies of systemic AEs compared to the CA vaccine and, historically, compared to the HuAd5 vectored malaria vaccine encoding CSP and AMA1, they were transient and associated with increased vector dosing. Medicine R Science Q Santina Maiolatesi verfasserin aut Noelle Patterson verfasserin aut Martha Sedegah verfasserin aut Keith Limbach verfasserin aut Nimfa Teneza-Mora verfasserin aut Ilin Chuang verfasserin aut K Monique Hollis-Perry verfasserin aut Jo Glenna Banania verfasserin aut Ivelese Guzman verfasserin aut Harini Ganeshan verfasserin aut Sharina Reyes verfasserin aut Michael R Hollingdale verfasserin aut Mimi Wong verfasserin aut Ashley Lindstrom verfasserin aut Anatalio Reyes verfasserin aut Yolanda Alcorta verfasserin aut Lindsey Garver verfasserin aut Kelli Bankard verfasserin aut Arnel Belmonte verfasserin aut Maria Belmonte verfasserin aut Jun Huang verfasserin aut Kalpana Gowda verfasserin aut Sandra Inoue verfasserin aut Rachel Velasco verfasserin aut Elke Bergmann-Leitner verfasserin aut Jack Hutter verfasserin aut Tida Lee verfasserin aut Nehkonti Adams verfasserin aut Sidhartha Chaudhury verfasserin aut Devin Hunt verfasserin aut Cindy Tamminga verfasserin aut Eleanor Berrie verfasserin aut Duncan Bellamy verfasserin aut Mustapha Bittaye verfasserin aut Katie Ewer verfasserin aut Carter Diggs verfasserin aut Lorraine A Soisson verfasserin aut Alison Lawrie verfasserin aut Adrian Hill verfasserin aut Thomas L Richie verfasserin aut Eileen Villasante verfasserin aut Judith E Epstein verfasserin aut Christopher A Duplessis verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 16(2021), 9, p e0256980 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:16 year:2021 number:9, p e0256980 https://doi.org/10.1371/journal.pone.0256980 kostenfrei https://doaj.org/article/4dc547617946467c9611eaa99d4458b4 kostenfrei https://doi.org/10.1371/journal.pone.0256980 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 9, p e0256980
spelling	10.1371/journal.pone.0256980 doi (DE-627)DOAJ051303698 (DE-599)DOAJ4dc547617946467c9611eaa99d4458b4 DE-627 ger DE-627 rakwb eng Marvin J Sklar verfasserin aut A three-antigen Plasmodium falciparum DNA prime-Adenovirus boost malaria vaccine regimen is superior to a two-antigen regimen and protects against controlled human malaria infection in healthy malaria-naïve adults. 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4<A DNA-prime/human adenovirus serotype 5 (HuAd5) boost vaccine encoding Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) and Pf apical membrane antigen-1 (PfAMA1), elicited protection in 4/15 (27%) of subjects against controlled human malaria infection (CHMI) that was statistically associated with CD8+ T cell responses. Subjects with high level pre-existing immunity to HuAd5 were not protected, suggesting an adverse effect on vaccine efficacy (VE). We replaced HuAd5 with chimpanzee adenovirus 63 (ChAd63), and repeated the study, assessing both the two-antigen (CSP, AMA1 = CA) vaccine, and a novel three-antigen (CSP, AMA1, ME-TRAP = CAT) vaccine that included a third pre-erythrocytic stage antigen [malaria multiple epitopes (ME) fused to the Pf thrombospondin-related adhesive protein (TRAP)] to potentially enhance protection.<h4<Methodology</h4<This was an open label, randomized Phase 1 trial, assessing safety, tolerability, and VE against CHMI in healthy, malaria naïve adults. Forty subjects (20 each group) were to receive three monthly CA or CAT DNA priming immunizations, followed by corresponding ChAd63 boost four months later. Four weeks after the boost, immunized subjects and 12 infectivity controls underwent CHMI by mosquito bite using the Pf3D7 strain. VE was assessed by determining the differences in time to parasitemia as detected by thick blood smears up to 28-days post CHMI and utilizing the log rank test, and by calculating the risk ratio of each treatment group and subtracting from 1, with significance calculated by the Cochran-Mantel-Haenszel method.<h4<Results</h4<In both groups, systemic adverse events (AEs) were significantly higher after the ChAd63 boost than DNA immunizations. Eleven of 12 infectivity controls developed parasitemia (mean 11.7 days). In the CA group, 15 of 16 (93.8%) immunized subjects developed parasitemia (mean 12.0 days). In the CAT group, 11 of 16 (63.8%) immunized subjects developed parasitemia (mean 13.0 days), indicating significant protection by log rank test compared to infectivity controls (p = 0.0406) and the CA group (p = 0.0229). VE (1 minus the risk ratio) in the CAT group was 25% compared to -2% in the CA group. The CA and CAT vaccines induced robust humoral (ELISA antibodies against CSP, AMA1 and TRAP, and IFA responses against sporozoites and Pf3D7 blood stages), and cellular responses (IFN-γ FluoroSpot responses to CSP, AMA1 and TRAP) that were not associated with protection.<h4<Conclusions</h4<This study demonstrated that the ChAd63 CAT vaccine exhibited significant protective efficacy, and confirmed protection was afforded by adding a third antigen (T) to a two-antigen (CA) formulation to achieve increased VE. Although the ChAd63-CAT vaccine was associated with increased frequencies of systemic AEs compared to the CA vaccine and, historically, compared to the HuAd5 vectored malaria vaccine encoding CSP and AMA1, they were transient and associated with increased vector dosing. Medicine R Science Q Santina Maiolatesi verfasserin aut Noelle Patterson verfasserin aut Martha Sedegah verfasserin aut Keith Limbach verfasserin aut Nimfa Teneza-Mora verfasserin aut Ilin Chuang verfasserin aut K Monique Hollis-Perry verfasserin aut Jo Glenna Banania verfasserin aut Ivelese Guzman verfasserin aut Harini Ganeshan verfasserin aut Sharina Reyes verfasserin aut Michael R Hollingdale verfasserin aut Mimi Wong verfasserin aut Ashley Lindstrom verfasserin aut Anatalio Reyes verfasserin aut Yolanda Alcorta verfasserin aut Lindsey Garver verfasserin aut Kelli Bankard verfasserin aut Arnel Belmonte verfasserin aut Maria Belmonte verfasserin aut Jun Huang verfasserin aut Kalpana Gowda verfasserin aut Sandra Inoue verfasserin aut Rachel Velasco verfasserin aut Elke Bergmann-Leitner verfasserin aut Jack Hutter verfasserin aut Tida Lee verfasserin aut Nehkonti Adams verfasserin aut Sidhartha Chaudhury verfasserin aut Devin Hunt verfasserin aut Cindy Tamminga verfasserin aut Eleanor Berrie verfasserin aut Duncan Bellamy verfasserin aut Mustapha Bittaye verfasserin aut Katie Ewer verfasserin aut Carter Diggs verfasserin aut Lorraine A Soisson verfasserin aut Alison Lawrie verfasserin aut Adrian Hill verfasserin aut Thomas L Richie verfasserin aut Eileen Villasante verfasserin aut Judith E Epstein verfasserin aut Christopher A Duplessis verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 16(2021), 9, p e0256980 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:16 year:2021 number:9, p e0256980 https://doi.org/10.1371/journal.pone.0256980 kostenfrei https://doaj.org/article/4dc547617946467c9611eaa99d4458b4 kostenfrei https://doi.org/10.1371/journal.pone.0256980 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 9, p e0256980
allfields_unstemmed	10.1371/journal.pone.0256980 doi (DE-627)DOAJ051303698 (DE-599)DOAJ4dc547617946467c9611eaa99d4458b4 DE-627 ger DE-627 rakwb eng Marvin J Sklar verfasserin aut A three-antigen Plasmodium falciparum DNA prime-Adenovirus boost malaria vaccine regimen is superior to a two-antigen regimen and protects against controlled human malaria infection in healthy malaria-naïve adults. 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4<A DNA-prime/human adenovirus serotype 5 (HuAd5) boost vaccine encoding Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) and Pf apical membrane antigen-1 (PfAMA1), elicited protection in 4/15 (27%) of subjects against controlled human malaria infection (CHMI) that was statistically associated with CD8+ T cell responses. Subjects with high level pre-existing immunity to HuAd5 were not protected, suggesting an adverse effect on vaccine efficacy (VE). We replaced HuAd5 with chimpanzee adenovirus 63 (ChAd63), and repeated the study, assessing both the two-antigen (CSP, AMA1 = CA) vaccine, and a novel three-antigen (CSP, AMA1, ME-TRAP = CAT) vaccine that included a third pre-erythrocytic stage antigen [malaria multiple epitopes (ME) fused to the Pf thrombospondin-related adhesive protein (TRAP)] to potentially enhance protection.<h4<Methodology</h4<This was an open label, randomized Phase 1 trial, assessing safety, tolerability, and VE against CHMI in healthy, malaria naïve adults. Forty subjects (20 each group) were to receive three monthly CA or CAT DNA priming immunizations, followed by corresponding ChAd63 boost four months later. Four weeks after the boost, immunized subjects and 12 infectivity controls underwent CHMI by mosquito bite using the Pf3D7 strain. VE was assessed by determining the differences in time to parasitemia as detected by thick blood smears up to 28-days post CHMI and utilizing the log rank test, and by calculating the risk ratio of each treatment group and subtracting from 1, with significance calculated by the Cochran-Mantel-Haenszel method.<h4<Results</h4<In both groups, systemic adverse events (AEs) were significantly higher after the ChAd63 boost than DNA immunizations. Eleven of 12 infectivity controls developed parasitemia (mean 11.7 days). In the CA group, 15 of 16 (93.8%) immunized subjects developed parasitemia (mean 12.0 days). In the CAT group, 11 of 16 (63.8%) immunized subjects developed parasitemia (mean 13.0 days), indicating significant protection by log rank test compared to infectivity controls (p = 0.0406) and the CA group (p = 0.0229). VE (1 minus the risk ratio) in the CAT group was 25% compared to -2% in the CA group. The CA and CAT vaccines induced robust humoral (ELISA antibodies against CSP, AMA1 and TRAP, and IFA responses against sporozoites and Pf3D7 blood stages), and cellular responses (IFN-γ FluoroSpot responses to CSP, AMA1 and TRAP) that were not associated with protection.<h4<Conclusions</h4<This study demonstrated that the ChAd63 CAT vaccine exhibited significant protective efficacy, and confirmed protection was afforded by adding a third antigen (T) to a two-antigen (CA) formulation to achieve increased VE. Although the ChAd63-CAT vaccine was associated with increased frequencies of systemic AEs compared to the CA vaccine and, historically, compared to the HuAd5 vectored malaria vaccine encoding CSP and AMA1, they were transient and associated with increased vector dosing. Medicine R Science Q Santina Maiolatesi verfasserin aut Noelle Patterson verfasserin aut Martha Sedegah verfasserin aut Keith Limbach verfasserin aut Nimfa Teneza-Mora verfasserin aut Ilin Chuang verfasserin aut K Monique Hollis-Perry verfasserin aut Jo Glenna Banania verfasserin aut Ivelese Guzman verfasserin aut Harini Ganeshan verfasserin aut Sharina Reyes verfasserin aut Michael R Hollingdale verfasserin aut Mimi Wong verfasserin aut Ashley Lindstrom verfasserin aut Anatalio Reyes verfasserin aut Yolanda Alcorta verfasserin aut Lindsey Garver verfasserin aut Kelli Bankard verfasserin aut Arnel Belmonte verfasserin aut Maria Belmonte verfasserin aut Jun Huang verfasserin aut Kalpana Gowda verfasserin aut Sandra Inoue verfasserin aut Rachel Velasco verfasserin aut Elke Bergmann-Leitner verfasserin aut Jack Hutter verfasserin aut Tida Lee verfasserin aut Nehkonti Adams verfasserin aut Sidhartha Chaudhury verfasserin aut Devin Hunt verfasserin aut Cindy Tamminga verfasserin aut Eleanor Berrie verfasserin aut Duncan Bellamy verfasserin aut Mustapha Bittaye verfasserin aut Katie Ewer verfasserin aut Carter Diggs verfasserin aut Lorraine A Soisson verfasserin aut Alison Lawrie verfasserin aut Adrian Hill verfasserin aut Thomas L Richie verfasserin aut Eileen Villasante verfasserin aut Judith E Epstein verfasserin aut Christopher A Duplessis verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 16(2021), 9, p e0256980 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:16 year:2021 number:9, p e0256980 https://doi.org/10.1371/journal.pone.0256980 kostenfrei https://doaj.org/article/4dc547617946467c9611eaa99d4458b4 kostenfrei https://doi.org/10.1371/journal.pone.0256980 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 9, p e0256980
allfieldsGer	10.1371/journal.pone.0256980 doi (DE-627)DOAJ051303698 (DE-599)DOAJ4dc547617946467c9611eaa99d4458b4 DE-627 ger DE-627 rakwb eng Marvin J Sklar verfasserin aut A three-antigen Plasmodium falciparum DNA prime-Adenovirus boost malaria vaccine regimen is superior to a two-antigen regimen and protects against controlled human malaria infection in healthy malaria-naïve adults. 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4<A DNA-prime/human adenovirus serotype 5 (HuAd5) boost vaccine encoding Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) and Pf apical membrane antigen-1 (PfAMA1), elicited protection in 4/15 (27%) of subjects against controlled human malaria infection (CHMI) that was statistically associated with CD8+ T cell responses. Subjects with high level pre-existing immunity to HuAd5 were not protected, suggesting an adverse effect on vaccine efficacy (VE). We replaced HuAd5 with chimpanzee adenovirus 63 (ChAd63), and repeated the study, assessing both the two-antigen (CSP, AMA1 = CA) vaccine, and a novel three-antigen (CSP, AMA1, ME-TRAP = CAT) vaccine that included a third pre-erythrocytic stage antigen [malaria multiple epitopes (ME) fused to the Pf thrombospondin-related adhesive protein (TRAP)] to potentially enhance protection.<h4<Methodology</h4<This was an open label, randomized Phase 1 trial, assessing safety, tolerability, and VE against CHMI in healthy, malaria naïve adults. Forty subjects (20 each group) were to receive three monthly CA or CAT DNA priming immunizations, followed by corresponding ChAd63 boost four months later. Four weeks after the boost, immunized subjects and 12 infectivity controls underwent CHMI by mosquito bite using the Pf3D7 strain. VE was assessed by determining the differences in time to parasitemia as detected by thick blood smears up to 28-days post CHMI and utilizing the log rank test, and by calculating the risk ratio of each treatment group and subtracting from 1, with significance calculated by the Cochran-Mantel-Haenszel method.<h4<Results</h4<In both groups, systemic adverse events (AEs) were significantly higher after the ChAd63 boost than DNA immunizations. Eleven of 12 infectivity controls developed parasitemia (mean 11.7 days). In the CA group, 15 of 16 (93.8%) immunized subjects developed parasitemia (mean 12.0 days). In the CAT group, 11 of 16 (63.8%) immunized subjects developed parasitemia (mean 13.0 days), indicating significant protection by log rank test compared to infectivity controls (p = 0.0406) and the CA group (p = 0.0229). VE (1 minus the risk ratio) in the CAT group was 25% compared to -2% in the CA group. The CA and CAT vaccines induced robust humoral (ELISA antibodies against CSP, AMA1 and TRAP, and IFA responses against sporozoites and Pf3D7 blood stages), and cellular responses (IFN-γ FluoroSpot responses to CSP, AMA1 and TRAP) that were not associated with protection.<h4<Conclusions</h4<This study demonstrated that the ChAd63 CAT vaccine exhibited significant protective efficacy, and confirmed protection was afforded by adding a third antigen (T) to a two-antigen (CA) formulation to achieve increased VE. Although the ChAd63-CAT vaccine was associated with increased frequencies of systemic AEs compared to the CA vaccine and, historically, compared to the HuAd5 vectored malaria vaccine encoding CSP and AMA1, they were transient and associated with increased vector dosing. Medicine R Science Q Santina Maiolatesi verfasserin aut Noelle Patterson verfasserin aut Martha Sedegah verfasserin aut Keith Limbach verfasserin aut Nimfa Teneza-Mora verfasserin aut Ilin Chuang verfasserin aut K Monique Hollis-Perry verfasserin aut Jo Glenna Banania verfasserin aut Ivelese Guzman verfasserin aut Harini Ganeshan verfasserin aut Sharina Reyes verfasserin aut Michael R Hollingdale verfasserin aut Mimi Wong verfasserin aut Ashley Lindstrom verfasserin aut Anatalio Reyes verfasserin aut Yolanda Alcorta verfasserin aut Lindsey Garver verfasserin aut Kelli Bankard verfasserin aut Arnel Belmonte verfasserin aut Maria Belmonte verfasserin aut Jun Huang verfasserin aut Kalpana Gowda verfasserin aut Sandra Inoue verfasserin aut Rachel Velasco verfasserin aut Elke Bergmann-Leitner verfasserin aut Jack Hutter verfasserin aut Tida Lee verfasserin aut Nehkonti Adams verfasserin aut Sidhartha Chaudhury verfasserin aut Devin Hunt verfasserin aut Cindy Tamminga verfasserin aut Eleanor Berrie verfasserin aut Duncan Bellamy verfasserin aut Mustapha Bittaye verfasserin aut Katie Ewer verfasserin aut Carter Diggs verfasserin aut Lorraine A Soisson verfasserin aut Alison Lawrie verfasserin aut Adrian Hill verfasserin aut Thomas L Richie verfasserin aut Eileen Villasante verfasserin aut Judith E Epstein verfasserin aut Christopher A Duplessis verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 16(2021), 9, p e0256980 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:16 year:2021 number:9, p e0256980 https://doi.org/10.1371/journal.pone.0256980 kostenfrei https://doaj.org/article/4dc547617946467c9611eaa99d4458b4 kostenfrei https://doi.org/10.1371/journal.pone.0256980 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 9, p e0256980
allfieldsSound	10.1371/journal.pone.0256980 doi (DE-627)DOAJ051303698 (DE-599)DOAJ4dc547617946467c9611eaa99d4458b4 DE-627 ger DE-627 rakwb eng Marvin J Sklar verfasserin aut A three-antigen Plasmodium falciparum DNA prime-Adenovirus boost malaria vaccine regimen is superior to a two-antigen regimen and protects against controlled human malaria infection in healthy malaria-naïve adults. 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <h4<Background</h4<A DNA-prime/human adenovirus serotype 5 (HuAd5) boost vaccine encoding Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) and Pf apical membrane antigen-1 (PfAMA1), elicited protection in 4/15 (27%) of subjects against controlled human malaria infection (CHMI) that was statistically associated with CD8+ T cell responses. Subjects with high level pre-existing immunity to HuAd5 were not protected, suggesting an adverse effect on vaccine efficacy (VE). We replaced HuAd5 with chimpanzee adenovirus 63 (ChAd63), and repeated the study, assessing both the two-antigen (CSP, AMA1 = CA) vaccine, and a novel three-antigen (CSP, AMA1, ME-TRAP = CAT) vaccine that included a third pre-erythrocytic stage antigen [malaria multiple epitopes (ME) fused to the Pf thrombospondin-related adhesive protein (TRAP)] to potentially enhance protection.<h4<Methodology</h4<This was an open label, randomized Phase 1 trial, assessing safety, tolerability, and VE against CHMI in healthy, malaria naïve adults. Forty subjects (20 each group) were to receive three monthly CA or CAT DNA priming immunizations, followed by corresponding ChAd63 boost four months later. Four weeks after the boost, immunized subjects and 12 infectivity controls underwent CHMI by mosquito bite using the Pf3D7 strain. VE was assessed by determining the differences in time to parasitemia as detected by thick blood smears up to 28-days post CHMI and utilizing the log rank test, and by calculating the risk ratio of each treatment group and subtracting from 1, with significance calculated by the Cochran-Mantel-Haenszel method.<h4<Results</h4<In both groups, systemic adverse events (AEs) were significantly higher after the ChAd63 boost than DNA immunizations. Eleven of 12 infectivity controls developed parasitemia (mean 11.7 days). In the CA group, 15 of 16 (93.8%) immunized subjects developed parasitemia (mean 12.0 days). In the CAT group, 11 of 16 (63.8%) immunized subjects developed parasitemia (mean 13.0 days), indicating significant protection by log rank test compared to infectivity controls (p = 0.0406) and the CA group (p = 0.0229). VE (1 minus the risk ratio) in the CAT group was 25% compared to -2% in the CA group. The CA and CAT vaccines induced robust humoral (ELISA antibodies against CSP, AMA1 and TRAP, and IFA responses against sporozoites and Pf3D7 blood stages), and cellular responses (IFN-γ FluoroSpot responses to CSP, AMA1 and TRAP) that were not associated with protection.<h4<Conclusions</h4<This study demonstrated that the ChAd63 CAT vaccine exhibited significant protective efficacy, and confirmed protection was afforded by adding a third antigen (T) to a two-antigen (CA) formulation to achieve increased VE. Although the ChAd63-CAT vaccine was associated with increased frequencies of systemic AEs compared to the CA vaccine and, historically, compared to the HuAd5 vectored malaria vaccine encoding CSP and AMA1, they were transient and associated with increased vector dosing. Medicine R Science Q Santina Maiolatesi verfasserin aut Noelle Patterson verfasserin aut Martha Sedegah verfasserin aut Keith Limbach verfasserin aut Nimfa Teneza-Mora verfasserin aut Ilin Chuang verfasserin aut K Monique Hollis-Perry verfasserin aut Jo Glenna Banania verfasserin aut Ivelese Guzman verfasserin aut Harini Ganeshan verfasserin aut Sharina Reyes verfasserin aut Michael R Hollingdale verfasserin aut Mimi Wong verfasserin aut Ashley Lindstrom verfasserin aut Anatalio Reyes verfasserin aut Yolanda Alcorta verfasserin aut Lindsey Garver verfasserin aut Kelli Bankard verfasserin aut Arnel Belmonte verfasserin aut Maria Belmonte verfasserin aut Jun Huang verfasserin aut Kalpana Gowda verfasserin aut Sandra Inoue verfasserin aut Rachel Velasco verfasserin aut Elke Bergmann-Leitner verfasserin aut Jack Hutter verfasserin aut Tida Lee verfasserin aut Nehkonti Adams verfasserin aut Sidhartha Chaudhury verfasserin aut Devin Hunt verfasserin aut Cindy Tamminga verfasserin aut Eleanor Berrie verfasserin aut Duncan Bellamy verfasserin aut Mustapha Bittaye verfasserin aut Katie Ewer verfasserin aut Carter Diggs verfasserin aut Lorraine A Soisson verfasserin aut Alison Lawrie verfasserin aut Adrian Hill verfasserin aut Thomas L Richie verfasserin aut Eileen Villasante verfasserin aut Judith E Epstein verfasserin aut Christopher A Duplessis verfasserin aut In PLoS ONE Public Library of Science (PLoS), 2007 16(2021), 9, p e0256980 (DE-627)523574592 (DE-600)2267670-3 19326203 nnns volume:16 year:2021 number:9, p e0256980 https://doi.org/10.1371/journal.pone.0256980 kostenfrei https://doaj.org/article/4dc547617946467c9611eaa99d4458b4 kostenfrei https://doi.org/10.1371/journal.pone.0256980 kostenfrei https://doaj.org/toc/1932-6203 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 9, p e0256980
language	English
source	In PLoS ONE 16(2021), 9, p e0256980 volume:16 year:2021 number:9, p e0256980
sourceStr	In PLoS ONE 16(2021), 9, p e0256980 volume:16 year:2021 number:9, p e0256980
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container_title	PLoS ONE
authorswithroles_txt_mv	Marvin J Sklar @@aut@@ Santina Maiolatesi @@aut@@ Noelle Patterson @@aut@@ Martha Sedegah @@aut@@ Keith Limbach @@aut@@ Nimfa Teneza-Mora @@aut@@ Ilin Chuang @@aut@@ K Monique Hollis-Perry @@aut@@ Jo Glenna Banania @@aut@@ Ivelese Guzman @@aut@@ Harini Ganeshan @@aut@@ Sharina Reyes @@aut@@ Michael R Hollingdale @@aut@@ Mimi Wong @@aut@@ Ashley Lindstrom @@aut@@ Anatalio Reyes @@aut@@ Yolanda Alcorta @@aut@@ Lindsey Garver @@aut@@ Kelli Bankard @@aut@@ Arnel Belmonte @@aut@@ Maria Belmonte @@aut@@ Jun Huang @@aut@@ Kalpana Gowda @@aut@@ Sandra Inoue @@aut@@ Rachel Velasco @@aut@@ Elke Bergmann-Leitner @@aut@@ Jack Hutter @@aut@@ Tida Lee @@aut@@ Nehkonti Adams @@aut@@ Sidhartha Chaudhury @@aut@@ Devin Hunt @@aut@@ Cindy Tamminga @@aut@@ Eleanor Berrie @@aut@@ Duncan Bellamy @@aut@@ Mustapha Bittaye @@aut@@ Katie Ewer @@aut@@ Carter Diggs @@aut@@ Lorraine A Soisson @@aut@@ Alison Lawrie @@aut@@ Adrian Hill @@aut@@ Thomas L Richie @@aut@@ Eileen Villasante @@aut@@ Judith E Epstein @@aut@@ Christopher A Duplessis @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	523574592
id	DOAJ051303698
language_de	englisch
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Subjects with high level pre-existing immunity to HuAd5 were not protected, suggesting an adverse effect on vaccine efficacy (VE). We replaced HuAd5 with chimpanzee adenovirus 63 (ChAd63), and repeated the study, assessing both the two-antigen (CSP, AMA1 = CA) vaccine, and a novel three-antigen (CSP, AMA1, ME-TRAP = CAT) vaccine that included a third pre-erythrocytic stage antigen [malaria multiple epitopes (ME) fused to the Pf thrombospondin-related adhesive protein (TRAP)] to potentially enhance protection.<h4<Methodology</h4<This was an open label, randomized Phase 1 trial, assessing safety, tolerability, and VE against CHMI in healthy, malaria naïve adults. Forty subjects (20 each group) were to receive three monthly CA or CAT DNA priming immunizations, followed by corresponding ChAd63 boost four months later. Four weeks after the boost, immunized subjects and 12 infectivity controls underwent CHMI by mosquito bite using the Pf3D7 strain. VE was assessed by determining the differences in time to parasitemia as detected by thick blood smears up to 28-days post CHMI and utilizing the log rank test, and by calculating the risk ratio of each treatment group and subtracting from 1, with significance calculated by the Cochran-Mantel-Haenszel method.<h4<Results</h4<In both groups, systemic adverse events (AEs) were significantly higher after the ChAd63 boost than DNA immunizations. Eleven of 12 infectivity controls developed parasitemia (mean 11.7 days). In the CA group, 15 of 16 (93.8%) immunized subjects developed parasitemia (mean 12.0 days). In the CAT group, 11 of 16 (63.8%) immunized subjects developed parasitemia (mean 13.0 days), indicating significant protection by log rank test compared to infectivity controls (p = 0.0406) and the CA group (p = 0.0229). VE (1 minus the risk ratio) in the CAT group was 25% compared to -2% in the CA group. The CA and CAT vaccines induced robust humoral (ELISA antibodies against CSP, AMA1 and TRAP, and IFA responses against sporozoites and Pf3D7 blood stages), and cellular responses (IFN-γ FluoroSpot responses to CSP, AMA1 and TRAP) that were not associated with protection.<h4<Conclusions</h4<This study demonstrated that the ChAd63 CAT vaccine exhibited significant protective efficacy, and confirmed protection was afforded by adding a third antigen (T) to a two-antigen (CA) formulation to achieve increased VE. 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author	Marvin J Sklar
spellingShingle	Marvin J Sklar misc Medicine misc R misc Science misc Q A three-antigen Plasmodium falciparum DNA prime-Adenovirus boost malaria vaccine regimen is superior to a two-antigen regimen and protects against controlled human malaria infection in healthy malaria-naïve adults.
authorStr	Marvin J Sklar
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topic_title	A three-antigen Plasmodium falciparum DNA prime-Adenovirus boost malaria vaccine regimen is superior to a two-antigen regimen and protects against controlled human malaria infection in healthy malaria-naïve adults
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title	A three-antigen Plasmodium falciparum DNA prime-Adenovirus boost malaria vaccine regimen is superior to a two-antigen regimen and protects against controlled human malaria infection in healthy malaria-naïve adults.
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title_full	A three-antigen Plasmodium falciparum DNA prime-Adenovirus boost malaria vaccine regimen is superior to a two-antigen regimen and protects against controlled human malaria infection in healthy malaria-naïve adults
author_sort	Marvin J Sklar
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author_browse	Marvin J Sklar Santina Maiolatesi Noelle Patterson Martha Sedegah Keith Limbach Nimfa Teneza-Mora Ilin Chuang K Monique Hollis-Perry Jo Glenna Banania Ivelese Guzman Harini Ganeshan Sharina Reyes Michael R Hollingdale Mimi Wong Ashley Lindstrom Anatalio Reyes Yolanda Alcorta Lindsey Garver Kelli Bankard Arnel Belmonte Maria Belmonte Jun Huang Kalpana Gowda Sandra Inoue Rachel Velasco Elke Bergmann-Leitner Jack Hutter Tida Lee Nehkonti Adams Sidhartha Chaudhury Devin Hunt Cindy Tamminga Eleanor Berrie Duncan Bellamy Mustapha Bittaye Katie Ewer Carter Diggs Lorraine A Soisson Alison Lawrie Adrian Hill Thomas L Richie Eileen Villasante Judith E Epstein Christopher A Duplessis
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author-letter	Marvin J Sklar
doi_str_mv	10.1371/journal.pone.0256980
author2-role	verfasserin
title_sort	three-antigen plasmodium falciparum dna prime-adenovirus boost malaria vaccine regimen is superior to a two-antigen regimen and protects against controlled human malaria infection in healthy malaria-naïve adults
title_auth	A three-antigen Plasmodium falciparum DNA prime-Adenovirus boost malaria vaccine regimen is superior to a two-antigen regimen and protects against controlled human malaria infection in healthy malaria-naïve adults.
abstract	<h4<Background</h4<A DNA-prime/human adenovirus serotype 5 (HuAd5) boost vaccine encoding Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) and Pf apical membrane antigen-1 (PfAMA1), elicited protection in 4/15 (27%) of subjects against controlled human malaria infection (CHMI) that was statistically associated with CD8+ T cell responses. Subjects with high level pre-existing immunity to HuAd5 were not protected, suggesting an adverse effect on vaccine efficacy (VE). We replaced HuAd5 with chimpanzee adenovirus 63 (ChAd63), and repeated the study, assessing both the two-antigen (CSP, AMA1 = CA) vaccine, and a novel three-antigen (CSP, AMA1, ME-TRAP = CAT) vaccine that included a third pre-erythrocytic stage antigen [malaria multiple epitopes (ME) fused to the Pf thrombospondin-related adhesive protein (TRAP)] to potentially enhance protection.<h4<Methodology</h4<This was an open label, randomized Phase 1 trial, assessing safety, tolerability, and VE against CHMI in healthy, malaria naïve adults. Forty subjects (20 each group) were to receive three monthly CA or CAT DNA priming immunizations, followed by corresponding ChAd63 boost four months later. Four weeks after the boost, immunized subjects and 12 infectivity controls underwent CHMI by mosquito bite using the Pf3D7 strain. VE was assessed by determining the differences in time to parasitemia as detected by thick blood smears up to 28-days post CHMI and utilizing the log rank test, and by calculating the risk ratio of each treatment group and subtracting from 1, with significance calculated by the Cochran-Mantel-Haenszel method.<h4<Results</h4<In both groups, systemic adverse events (AEs) were significantly higher after the ChAd63 boost than DNA immunizations. Eleven of 12 infectivity controls developed parasitemia (mean 11.7 days). In the CA group, 15 of 16 (93.8%) immunized subjects developed parasitemia (mean 12.0 days). In the CAT group, 11 of 16 (63.8%) immunized subjects developed parasitemia (mean 13.0 days), indicating significant protection by log rank test compared to infectivity controls (p = 0.0406) and the CA group (p = 0.0229). VE (1 minus the risk ratio) in the CAT group was 25% compared to -2% in the CA group. The CA and CAT vaccines induced robust humoral (ELISA antibodies against CSP, AMA1 and TRAP, and IFA responses against sporozoites and Pf3D7 blood stages), and cellular responses (IFN-γ FluoroSpot responses to CSP, AMA1 and TRAP) that were not associated with protection.<h4<Conclusions</h4<This study demonstrated that the ChAd63 CAT vaccine exhibited significant protective efficacy, and confirmed protection was afforded by adding a third antigen (T) to a two-antigen (CA) formulation to achieve increased VE. Although the ChAd63-CAT vaccine was associated with increased frequencies of systemic AEs compared to the CA vaccine and, historically, compared to the HuAd5 vectored malaria vaccine encoding CSP and AMA1, they were transient and associated with increased vector dosing.
abstractGer	<h4<Background</h4<A DNA-prime/human adenovirus serotype 5 (HuAd5) boost vaccine encoding Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) and Pf apical membrane antigen-1 (PfAMA1), elicited protection in 4/15 (27%) of subjects against controlled human malaria infection (CHMI) that was statistically associated with CD8+ T cell responses. Subjects with high level pre-existing immunity to HuAd5 were not protected, suggesting an adverse effect on vaccine efficacy (VE). We replaced HuAd5 with chimpanzee adenovirus 63 (ChAd63), and repeated the study, assessing both the two-antigen (CSP, AMA1 = CA) vaccine, and a novel three-antigen (CSP, AMA1, ME-TRAP = CAT) vaccine that included a third pre-erythrocytic stage antigen [malaria multiple epitopes (ME) fused to the Pf thrombospondin-related adhesive protein (TRAP)] to potentially enhance protection.<h4<Methodology</h4<This was an open label, randomized Phase 1 trial, assessing safety, tolerability, and VE against CHMI in healthy, malaria naïve adults. Forty subjects (20 each group) were to receive three monthly CA or CAT DNA priming immunizations, followed by corresponding ChAd63 boost four months later. Four weeks after the boost, immunized subjects and 12 infectivity controls underwent CHMI by mosquito bite using the Pf3D7 strain. VE was assessed by determining the differences in time to parasitemia as detected by thick blood smears up to 28-days post CHMI and utilizing the log rank test, and by calculating the risk ratio of each treatment group and subtracting from 1, with significance calculated by the Cochran-Mantel-Haenszel method.<h4<Results</h4<In both groups, systemic adverse events (AEs) were significantly higher after the ChAd63 boost than DNA immunizations. Eleven of 12 infectivity controls developed parasitemia (mean 11.7 days). In the CA group, 15 of 16 (93.8%) immunized subjects developed parasitemia (mean 12.0 days). In the CAT group, 11 of 16 (63.8%) immunized subjects developed parasitemia (mean 13.0 days), indicating significant protection by log rank test compared to infectivity controls (p = 0.0406) and the CA group (p = 0.0229). VE (1 minus the risk ratio) in the CAT group was 25% compared to -2% in the CA group. The CA and CAT vaccines induced robust humoral (ELISA antibodies against CSP, AMA1 and TRAP, and IFA responses against sporozoites and Pf3D7 blood stages), and cellular responses (IFN-γ FluoroSpot responses to CSP, AMA1 and TRAP) that were not associated with protection.<h4<Conclusions</h4<This study demonstrated that the ChAd63 CAT vaccine exhibited significant protective efficacy, and confirmed protection was afforded by adding a third antigen (T) to a two-antigen (CA) formulation to achieve increased VE. Although the ChAd63-CAT vaccine was associated with increased frequencies of systemic AEs compared to the CA vaccine and, historically, compared to the HuAd5 vectored malaria vaccine encoding CSP and AMA1, they were transient and associated with increased vector dosing.
abstract_unstemmed	<h4<Background</h4<A DNA-prime/human adenovirus serotype 5 (HuAd5) boost vaccine encoding Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) and Pf apical membrane antigen-1 (PfAMA1), elicited protection in 4/15 (27%) of subjects against controlled human malaria infection (CHMI) that was statistically associated with CD8+ T cell responses. Subjects with high level pre-existing immunity to HuAd5 were not protected, suggesting an adverse effect on vaccine efficacy (VE). We replaced HuAd5 with chimpanzee adenovirus 63 (ChAd63), and repeated the study, assessing both the two-antigen (CSP, AMA1 = CA) vaccine, and a novel three-antigen (CSP, AMA1, ME-TRAP = CAT) vaccine that included a third pre-erythrocytic stage antigen [malaria multiple epitopes (ME) fused to the Pf thrombospondin-related adhesive protein (TRAP)] to potentially enhance protection.<h4<Methodology</h4<This was an open label, randomized Phase 1 trial, assessing safety, tolerability, and VE against CHMI in healthy, malaria naïve adults. Forty subjects (20 each group) were to receive three monthly CA or CAT DNA priming immunizations, followed by corresponding ChAd63 boost four months later. Four weeks after the boost, immunized subjects and 12 infectivity controls underwent CHMI by mosquito bite using the Pf3D7 strain. VE was assessed by determining the differences in time to parasitemia as detected by thick blood smears up to 28-days post CHMI and utilizing the log rank test, and by calculating the risk ratio of each treatment group and subtracting from 1, with significance calculated by the Cochran-Mantel-Haenszel method.<h4<Results</h4<In both groups, systemic adverse events (AEs) were significantly higher after the ChAd63 boost than DNA immunizations. Eleven of 12 infectivity controls developed parasitemia (mean 11.7 days). In the CA group, 15 of 16 (93.8%) immunized subjects developed parasitemia (mean 12.0 days). In the CAT group, 11 of 16 (63.8%) immunized subjects developed parasitemia (mean 13.0 days), indicating significant protection by log rank test compared to infectivity controls (p = 0.0406) and the CA group (p = 0.0229). VE (1 minus the risk ratio) in the CAT group was 25% compared to -2% in the CA group. The CA and CAT vaccines induced robust humoral (ELISA antibodies against CSP, AMA1 and TRAP, and IFA responses against sporozoites and Pf3D7 blood stages), and cellular responses (IFN-γ FluoroSpot responses to CSP, AMA1 and TRAP) that were not associated with protection.<h4<Conclusions</h4<This study demonstrated that the ChAd63 CAT vaccine exhibited significant protective efficacy, and confirmed protection was afforded by adding a third antigen (T) to a two-antigen (CA) formulation to achieve increased VE. Although the ChAd63-CAT vaccine was associated with increased frequencies of systemic AEs compared to the CA vaccine and, historically, compared to the HuAd5 vectored malaria vaccine encoding CSP and AMA1, they were transient and associated with increased vector dosing.
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container_issue	9, p e0256980
title_short	A three-antigen Plasmodium falciparum DNA prime-Adenovirus boost malaria vaccine regimen is superior to a two-antigen regimen and protects against controlled human malaria infection in healthy malaria-naïve adults.
url	https://doi.org/10.1371/journal.pone.0256980 https://doaj.org/article/4dc547617946467c9611eaa99d4458b4 https://doaj.org/toc/1932-6203
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author2	Santina Maiolatesi Noelle Patterson Martha Sedegah Keith Limbach Nimfa Teneza-Mora Ilin Chuang K Monique Hollis-Perry Jo Glenna Banania Ivelese Guzman Harini Ganeshan Sharina Reyes Michael R Hollingdale Mimi Wong Ashley Lindstrom Anatalio Reyes Yolanda Alcorta Lindsey Garver Kelli Bankard Arnel Belmonte Maria Belmonte Jun Huang Kalpana Gowda Sandra Inoue Rachel Velasco Elke Bergmann-Leitner Jack Hutter Tida Lee Nehkonti Adams Sidhartha Chaudhury Devin Hunt Cindy Tamminga Eleanor Berrie Duncan Bellamy Mustapha Bittaye Katie Ewer Carter Diggs Lorraine A Soisson Alison Lawrie Adrian Hill Thomas L Richie Eileen Villasante Judith E Epstein Christopher A Duplessis
author2Str	Santina Maiolatesi Noelle Patterson Martha Sedegah Keith Limbach Nimfa Teneza-Mora Ilin Chuang K Monique Hollis-Perry Jo Glenna Banania Ivelese Guzman Harini Ganeshan Sharina Reyes Michael R Hollingdale Mimi Wong Ashley Lindstrom Anatalio Reyes Yolanda Alcorta Lindsey Garver Kelli Bankard Arnel Belmonte Maria Belmonte Jun Huang Kalpana Gowda Sandra Inoue Rachel Velasco Elke Bergmann-Leitner Jack Hutter Tida Lee Nehkonti Adams Sidhartha Chaudhury Devin Hunt Cindy Tamminga Eleanor Berrie Duncan Bellamy Mustapha Bittaye Katie Ewer Carter Diggs Lorraine A Soisson Alison Lawrie Adrian Hill Thomas L Richie Eileen Villasante Judith E Epstein Christopher A Duplessis
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up_date	2024-07-03T19:34:00.501Z
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A three-antigen Plasmodium falciparum DNA prime-Adenovirus boost malaria vaccine regimen is superior to a two-antigen regimen and protects against controlled human malaria infection in healthy malaria-naïve adults.

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