Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination
Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Usin...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Tam, Hok Hei [verfasserIn] |
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| Format: |
Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2016 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Proceedings of the National Academy of Sciences of the United States of America - Washington, DC : NAS, 1877, 113(2016), 43, Seite E6639-E6648 |
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| Übergeordnetes Werk: |
volume:113 ; year:2016 ; number:43 ; pages:E6639-E6648 |
| Links: |
|---|
| DOI / URN: |
10.1073/pnas.1606050113 |
|---|
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OLC1986419649 |
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| 520 | |a Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1-2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime. Computational modeling of the germinal center response suggested that antigen availability as higher-affinity antibodies evolve enhances antigen capture in lymph nodes. Consistent with these predictions, we found that exp-inc dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant kinetics may enable increased vaccine potency. | ||
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| 650 | 4 | |a Immunoglobulins | |
| 700 | 1 | |a Melo, Mariane B |4 oth | |
| 700 | 1 | |a Kang, Myungsun |4 oth | |
| 700 | 1 | |a Pelet, Jeisa M |4 oth | |
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| 700 | 1 | |a Foley, Maria H |4 oth | |
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| 700 | 1 | |a Kumari, Sudha |4 oth | |
| 700 | 1 | |a Crampton, Jordan |4 oth | |
| 700 | 1 | |a Baldeon, Alexis D |4 oth | |
| 700 | 1 | |a Sanders, Rogier W |4 oth | |
| 700 | 1 | |a Moore, John P |4 oth | |
| 700 | 1 | |a Crotty, Shane |4 oth | |
| 700 | 1 | |a Langer, Robert |4 oth | |
| 700 | 1 | |a Anderson, Daniel G |4 oth | |
| 700 | 1 | |a Chakraborty, Arup K |4 oth | |
| 700 | 1 | |a Irvine, Darrell J |4 oth | |
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10.1073/pnas.1606050113 doi PQ20161201 (DE-627)OLC1986419649 (DE-599)GBVOLC1986419649 (PRQ)c1284-a2293bf64d55e45d973c14c13e3eb21ac3e634ed87360f3c51af4872468378130 (KEY)0583363920160000113004306639sustainedantigenavailabilityduringgerminalcenterin DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Tam, Hok Hei verfasserin aut Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1-2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime. Computational modeling of the germinal center response suggested that antigen availability as higher-affinity antibodies evolve enhances antigen capture in lymph nodes. Consistent with these predictions, we found that exp-inc dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant kinetics may enable increased vaccine potency. Antigens Immunization Immune system Infections Inflammation Immunoglobulins Melo, Mariane B oth Kang, Myungsun oth Pelet, Jeisa M oth Ruda, Vera M oth Foley, Maria H oth Hu, Joyce K oth Kumari, Sudha oth Crampton, Jordan oth Baldeon, Alexis D oth Sanders, Rogier W oth Moore, John P oth Crotty, Shane oth Langer, Robert oth Anderson, Daniel G oth Chakraborty, Arup K oth Irvine, Darrell J oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 113(2016), 43, Seite E6639-E6648 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:113 year:2016 number:43 pages:E6639-E6648 http://dx.doi.org/10.1073/pnas.1606050113 Volltext http://search.proquest.com/docview/1835926070 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 113 2016 43 E6639-E6648 |
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10.1073/pnas.1606050113 doi PQ20161201 (DE-627)OLC1986419649 (DE-599)GBVOLC1986419649 (PRQ)c1284-a2293bf64d55e45d973c14c13e3eb21ac3e634ed87360f3c51af4872468378130 (KEY)0583363920160000113004306639sustainedantigenavailabilityduringgerminalcenterin DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Tam, Hok Hei verfasserin aut Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1-2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime. Computational modeling of the germinal center response suggested that antigen availability as higher-affinity antibodies evolve enhances antigen capture in lymph nodes. Consistent with these predictions, we found that exp-inc dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant kinetics may enable increased vaccine potency. Antigens Immunization Immune system Infections Inflammation Immunoglobulins Melo, Mariane B oth Kang, Myungsun oth Pelet, Jeisa M oth Ruda, Vera M oth Foley, Maria H oth Hu, Joyce K oth Kumari, Sudha oth Crampton, Jordan oth Baldeon, Alexis D oth Sanders, Rogier W oth Moore, John P oth Crotty, Shane oth Langer, Robert oth Anderson, Daniel G oth Chakraborty, Arup K oth Irvine, Darrell J oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 113(2016), 43, Seite E6639-E6648 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:113 year:2016 number:43 pages:E6639-E6648 http://dx.doi.org/10.1073/pnas.1606050113 Volltext http://search.proquest.com/docview/1835926070 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 113 2016 43 E6639-E6648 |
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10.1073/pnas.1606050113 doi PQ20161201 (DE-627)OLC1986419649 (DE-599)GBVOLC1986419649 (PRQ)c1284-a2293bf64d55e45d973c14c13e3eb21ac3e634ed87360f3c51af4872468378130 (KEY)0583363920160000113004306639sustainedantigenavailabilityduringgerminalcenterin DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Tam, Hok Hei verfasserin aut Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1-2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime. Computational modeling of the germinal center response suggested that antigen availability as higher-affinity antibodies evolve enhances antigen capture in lymph nodes. Consistent with these predictions, we found that exp-inc dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant kinetics may enable increased vaccine potency. Antigens Immunization Immune system Infections Inflammation Immunoglobulins Melo, Mariane B oth Kang, Myungsun oth Pelet, Jeisa M oth Ruda, Vera M oth Foley, Maria H oth Hu, Joyce K oth Kumari, Sudha oth Crampton, Jordan oth Baldeon, Alexis D oth Sanders, Rogier W oth Moore, John P oth Crotty, Shane oth Langer, Robert oth Anderson, Daniel G oth Chakraborty, Arup K oth Irvine, Darrell J oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 113(2016), 43, Seite E6639-E6648 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:113 year:2016 number:43 pages:E6639-E6648 http://dx.doi.org/10.1073/pnas.1606050113 Volltext http://search.proquest.com/docview/1835926070 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 113 2016 43 E6639-E6648 |
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10.1073/pnas.1606050113 doi PQ20161201 (DE-627)OLC1986419649 (DE-599)GBVOLC1986419649 (PRQ)c1284-a2293bf64d55e45d973c14c13e3eb21ac3e634ed87360f3c51af4872468378130 (KEY)0583363920160000113004306639sustainedantigenavailabilityduringgerminalcenterin DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Tam, Hok Hei verfasserin aut Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1-2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime. Computational modeling of the germinal center response suggested that antigen availability as higher-affinity antibodies evolve enhances antigen capture in lymph nodes. Consistent with these predictions, we found that exp-inc dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant kinetics may enable increased vaccine potency. Antigens Immunization Immune system Infections Inflammation Immunoglobulins Melo, Mariane B oth Kang, Myungsun oth Pelet, Jeisa M oth Ruda, Vera M oth Foley, Maria H oth Hu, Joyce K oth Kumari, Sudha oth Crampton, Jordan oth Baldeon, Alexis D oth Sanders, Rogier W oth Moore, John P oth Crotty, Shane oth Langer, Robert oth Anderson, Daniel G oth Chakraborty, Arup K oth Irvine, Darrell J oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 113(2016), 43, Seite E6639-E6648 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:113 year:2016 number:43 pages:E6639-E6648 http://dx.doi.org/10.1073/pnas.1606050113 Volltext http://search.proquest.com/docview/1835926070 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 113 2016 43 E6639-E6648 |
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10.1073/pnas.1606050113 doi PQ20161201 (DE-627)OLC1986419649 (DE-599)GBVOLC1986419649 (PRQ)c1284-a2293bf64d55e45d973c14c13e3eb21ac3e634ed87360f3c51af4872468378130 (KEY)0583363920160000113004306639sustainedantigenavailabilityduringgerminalcenterin DE-627 ger DE-627 rakwb eng 500 DNB 570 AVZ LING fid BIODIV fid Tam, Hok Hei verfasserin aut Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination 2016 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1-2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime. Computational modeling of the germinal center response suggested that antigen availability as higher-affinity antibodies evolve enhances antigen capture in lymph nodes. Consistent with these predictions, we found that exp-inc dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant kinetics may enable increased vaccine potency. Antigens Immunization Immune system Infections Inflammation Immunoglobulins Melo, Mariane B oth Kang, Myungsun oth Pelet, Jeisa M oth Ruda, Vera M oth Foley, Maria H oth Hu, Joyce K oth Kumari, Sudha oth Crampton, Jordan oth Baldeon, Alexis D oth Sanders, Rogier W oth Moore, John P oth Crotty, Shane oth Langer, Robert oth Anderson, Daniel G oth Chakraborty, Arup K oth Irvine, Darrell J oth Enthalten in Proceedings of the National Academy of Sciences of the United States of America Washington, DC : NAS, 1877 113(2016), 43, Seite E6639-E6648 (DE-627)129505269 (DE-600)209104-5 (DE-576)014909189 0027-8424 nnns volume:113 year:2016 number:43 pages:E6639-E6648 http://dx.doi.org/10.1073/pnas.1606050113 Volltext http://search.proquest.com/docview/1835926070 GBV_USEFLAG_A SYSFLAG_A GBV_OLC FID-LING FID-BIODIV SSG-OLC-PHY SSG-OLC-CHE SSG-OLC-MAT SSG-OLC-FOR SSG-OLC-PHA SSG-OLC-DE-84 SSG-OPC-MAT SSG-OPC-FOR GBV_ILN_40 GBV_ILN_59 AR 113 2016 43 E6639-E6648 |
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Tam, Hok Hei @@aut@@ Melo, Mariane B @@oth@@ Kang, Myungsun @@oth@@ Pelet, Jeisa M @@oth@@ Ruda, Vera M @@oth@@ Foley, Maria H @@oth@@ Hu, Joyce K @@oth@@ Kumari, Sudha @@oth@@ Crampton, Jordan @@oth@@ Baldeon, Alexis D @@oth@@ Sanders, Rogier W @@oth@@ Moore, John P @@oth@@ Crotty, Shane @@oth@@ Langer, Robert @@oth@@ Anderson, Daniel G @@oth@@ Chakraborty, Arup K @@oth@@ Irvine, Darrell J @@oth@@ |
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Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination |
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Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1-2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime. Computational modeling of the germinal center response suggested that antigen availability as higher-affinity antibodies evolve enhances antigen capture in lymph nodes. Consistent with these predictions, we found that exp-inc dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant kinetics may enable increased vaccine potency. |
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Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1-2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime. Computational modeling of the germinal center response suggested that antigen availability as higher-affinity antibodies evolve enhances antigen capture in lymph nodes. Consistent with these predictions, we found that exp-inc dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant kinetics may enable increased vaccine potency. |
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Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1-2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime. Computational modeling of the germinal center response suggested that antigen availability as higher-affinity antibodies evolve enhances antigen capture in lymph nodes. Consistent with these predictions, we found that exp-inc dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant kinetics may enable increased vaccine potency. |
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