Targeting dendritic cells to accelerate T-cell activation overcomes a bottleneck in tuberculosis vaccine efficacy
The development of a tuberculosis (TB) vaccine that induces sterilizing immunity to Mycobacterium tuberculosis infection has been elusive. Absence of sterilizing immunity induced by TB vaccines may be due to delayed activation of mucosal dendritic cells (DCs), and subsequent delay in antigen present...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Springer Nature
2017
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| Online Access: | http://hdl.handle.net/1721.1/107719 |
| _version_ | 1826193978563756032 |
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| author | Griffiths, Kristin L. Ahmed, Mushtaq Das, Shibali Gopal, Radha Horne, William Connell, Terry D. Kolls, Jay K. Artyomov, Maxim N. Rangel-Moreno, Javier Khader, Shabaana A. Moynihan, Kelly Dare Irvine, Darrell J |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Griffiths, Kristin L. Ahmed, Mushtaq Das, Shibali Gopal, Radha Horne, William Connell, Terry D. Kolls, Jay K. Artyomov, Maxim N. Rangel-Moreno, Javier Khader, Shabaana A. Moynihan, Kelly Dare Irvine, Darrell J |
| author_sort | Griffiths, Kristin L. |
| collection | MIT |
| description | The development of a tuberculosis (TB) vaccine that induces sterilizing immunity to Mycobacterium tuberculosis infection has been elusive. Absence of sterilizing immunity induced by TB vaccines may be due to delayed activation of mucosal dendritic cells (DCs), and subsequent delay in antigen presentation and activation of vaccine-induced CD4[superscript +] T-cell responses. Here we show that pulmonary delivery of activated M. tuberculosis antigen-primed DCs into vaccinated mice, at the time of M. tuberculosis exposure, can overcome the delay in accumulation of vaccine-induced CD4[superscript +] T-cell responses. In addition, activating endogenous host CD103[superscript +] DCs and the CD40–CD40L pathway can similarly induce rapid accumulation of vaccine-induced lung CD4[superscript +] T-cell responses and limit early M. tuberculosis growth. Thus, our study provides proof of concept that targeting mucosal DCs can accelerate vaccine-induced T-cell responses on M. tuberculosis infection, and provide insights to overcome bottlenecks in TB vaccine efficacy. |
| first_indexed | 2024-09-23T09:48:40Z |
| format | Article |
| id | mit-1721.1/107719 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:48:40Z |
| publishDate | 2017 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | mit-1721.1/1077192022-09-26T13:53:49Z Targeting dendritic cells to accelerate T-cell activation overcomes a bottleneck in tuberculosis vaccine efficacy Griffiths, Kristin L. Ahmed, Mushtaq Das, Shibali Gopal, Radha Horne, William Connell, Terry D. Kolls, Jay K. Artyomov, Maxim N. Rangel-Moreno, Javier Khader, Shabaana A. Moynihan, Kelly Dare Irvine, Darrell J Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Materials Science and Engineering Moynihan, Kelly Dare Irvine, Darrell J The development of a tuberculosis (TB) vaccine that induces sterilizing immunity to Mycobacterium tuberculosis infection has been elusive. Absence of sterilizing immunity induced by TB vaccines may be due to delayed activation of mucosal dendritic cells (DCs), and subsequent delay in antigen presentation and activation of vaccine-induced CD4[superscript +] T-cell responses. Here we show that pulmonary delivery of activated M. tuberculosis antigen-primed DCs into vaccinated mice, at the time of M. tuberculosis exposure, can overcome the delay in accumulation of vaccine-induced CD4[superscript +] T-cell responses. In addition, activating endogenous host CD103[superscript +] DCs and the CD40–CD40L pathway can similarly induce rapid accumulation of vaccine-induced lung CD4[superscript +] T-cell responses and limit early M. tuberculosis growth. Thus, our study provides proof of concept that targeting mucosal DCs can accelerate vaccine-induced T-cell responses on M. tuberculosis infection, and provide insights to overcome bottlenecks in TB vaccine efficacy. National Institutes of Health (U.S.) (grant HL105427) National Institutes of Health (U.S.) (grant AI127172) United States. Army Research Office. Institute for Soldier Nanotechnologies (contract W911NF-13-D-0001) Howard Hughes Medical Institute (Investigator) 2017-03-27T15:20:19Z 2017-03-27T15:20:19Z 2016-12 2016-04 Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/107719 Griffiths, Kristin L., Mushtaq Ahmed, Shibali Das, Radha Gopal, William Horne, Terry D. Connell, Kelly D. Moynihan, et al. “Targeting Dendritic Cells to Accelerate T-Cell Activation Overcomes a Bottleneck in Tuberculosis Vaccine Efficacy.” Nature Communications 7 (December 22, 2016): 13894. en_US http://dx.doi.org/10.1038/ncomms13894 Nature Communications Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Springer Nature Nature |
| spellingShingle | Griffiths, Kristin L. Ahmed, Mushtaq Das, Shibali Gopal, Radha Horne, William Connell, Terry D. Kolls, Jay K. Artyomov, Maxim N. Rangel-Moreno, Javier Khader, Shabaana A. Moynihan, Kelly Dare Irvine, Darrell J Targeting dendritic cells to accelerate T-cell activation overcomes a bottleneck in tuberculosis vaccine efficacy |
| title | Targeting dendritic cells to accelerate T-cell activation overcomes a bottleneck in tuberculosis vaccine efficacy |
| title_full | Targeting dendritic cells to accelerate T-cell activation overcomes a bottleneck in tuberculosis vaccine efficacy |
| title_fullStr | Targeting dendritic cells to accelerate T-cell activation overcomes a bottleneck in tuberculosis vaccine efficacy |
| title_full_unstemmed | Targeting dendritic cells to accelerate T-cell activation overcomes a bottleneck in tuberculosis vaccine efficacy |
| title_short | Targeting dendritic cells to accelerate T-cell activation overcomes a bottleneck in tuberculosis vaccine efficacy |
| title_sort | targeting dendritic cells to accelerate t cell activation overcomes a bottleneck in tuberculosis vaccine efficacy |
| url | http://hdl.handle.net/1721.1/107719 |
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