Immunogenicity without efficacy of an adenoviral tuberculosis vaccine in a stringent mouse model for immunotherapy during treatment

S. Anisah Alyahya; Scott T. Nolan; Cara M.R. Smith; William R. Bishai; Jerald Sadoff; Gyanu Lamichhane

doi:10.1371/journal.pone.0127907

Immunogenicity without efficacy of an adenoviral tuberculosis vaccine in a stringent mouse model for immunotherapy during treatment

S. Anisah Alyahya, Scott T. Nolan, Cara M.R. Smith, William R. Bishai, Jerald Sadoff, Gyanu Lamichhane

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

To investigate if bacterial persistence during TB drug treatment could be overcome by modulation of host immunity, we adapted a clinically-relevant model developed for the evaluation of new drugs and examined if immunotherapy with two adenoviral vaccines, Ad35-TBS (AERAS-402) and Ad26-TBS, could shorten therapy in mice. Even though immunotherapy resulted in strong splenic IFN-γ responses, no effect on bacterial replication in the lungs was seen. Multiplex assay analysis of lung samples revealed the absence of cytokine augmentation such as IFN-γ, TNF-α and IL-2, suggesting that immunization failed to induce immunity in the lungs. In this model, we show that IFN-γ levels were not associated with protection against disease relapse. The results obtained from our study raise questions regarding the traits of protective TB immunity that are relevant for the development of future immunotherapeutic and post-exposure vaccination strategies.

Original language	English (US)
Article number	e0127907
Journal	PloS one
Volume	10
Issue number	5
DOIs	https://doi.org/10.1371/journal.pone.0127907
State	Published - May 21 2015

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology
General Agricultural and Biological Sciences
General

Access to Document

10.1371/journal.pone.0127907

Cite this

@article{f2d26ab8cb764c65a433ba4407974357,

title = "Immunogenicity without efficacy of an adenoviral tuberculosis vaccine in a stringent mouse model for immunotherapy during treatment",

abstract = "To investigate if bacterial persistence during TB drug treatment could be overcome by modulation of host immunity, we adapted a clinically-relevant model developed for the evaluation of new drugs and examined if immunotherapy with two adenoviral vaccines, Ad35-TBS (AERAS-402) and Ad26-TBS, could shorten therapy in mice. Even though immunotherapy resulted in strong splenic IFN-γ responses, no effect on bacterial replication in the lungs was seen. Multiplex assay analysis of lung samples revealed the absence of cytokine augmentation such as IFN-γ, TNF-α and IL-2, suggesting that immunization failed to induce immunity in the lungs. In this model, we show that IFN-γ levels were not associated with protection against disease relapse. The results obtained from our study raise questions regarding the traits of protective TB immunity that are relevant for the development of future immunotherapeutic and post-exposure vaccination strategies.",

author = "Alyahya, {S. Anisah} and Nolan, {Scott T.} and Smith, {Cara M.R.} and Bishai, {William R.} and Jerald Sadoff and Gyanu Lamichhane",

note = "Funding Information: I have read the journal's policy and the authors of this manuscript have the following competing interests: The study was funded by an internal grant from Crucell Holland BV. JS and SAA are current and former employees of Crucell Holland BV, respectively. JS and SAA have been awarded a United States Patent (US 8,771,709 B2) on the use of Ad35-TBS and Ad26-TBS as therapeutic vaccines. This does not alter the authors{\textquoteright} adherence to PLOS ONE policies on sharing data and materials. Publisher Copyright: {\textcopyright} 2015 Alyahya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2015",

month = may,

day = "21",

doi = "10.1371/journal.pone.0127907",

language = "English (US)",

volume = "10",

journal = "PloS one",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "5",

}

TY - JOUR

T1 - Immunogenicity without efficacy of an adenoviral tuberculosis vaccine in a stringent mouse model for immunotherapy during treatment

AU - Alyahya, S. Anisah

AU - Nolan, Scott T.

AU - Smith, Cara M.R.

AU - Bishai, William R.

AU - Sadoff, Jerald

AU - Lamichhane, Gyanu

N1 - Funding Information: I have read the journal's policy and the authors of this manuscript have the following competing interests: The study was funded by an internal grant from Crucell Holland BV. JS and SAA are current and former employees of Crucell Holland BV, respectively. JS and SAA have been awarded a United States Patent (US 8,771,709 B2) on the use of Ad35-TBS and Ad26-TBS as therapeutic vaccines. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials. Publisher Copyright: © 2015 Alyahya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2015/5/21

Y1 - 2015/5/21

N2 - To investigate if bacterial persistence during TB drug treatment could be overcome by modulation of host immunity, we adapted a clinically-relevant model developed for the evaluation of new drugs and examined if immunotherapy with two adenoviral vaccines, Ad35-TBS (AERAS-402) and Ad26-TBS, could shorten therapy in mice. Even though immunotherapy resulted in strong splenic IFN-γ responses, no effect on bacterial replication in the lungs was seen. Multiplex assay analysis of lung samples revealed the absence of cytokine augmentation such as IFN-γ, TNF-α and IL-2, suggesting that immunization failed to induce immunity in the lungs. In this model, we show that IFN-γ levels were not associated with protection against disease relapse. The results obtained from our study raise questions regarding the traits of protective TB immunity that are relevant for the development of future immunotherapeutic and post-exposure vaccination strategies.

AB - To investigate if bacterial persistence during TB drug treatment could be overcome by modulation of host immunity, we adapted a clinically-relevant model developed for the evaluation of new drugs and examined if immunotherapy with two adenoviral vaccines, Ad35-TBS (AERAS-402) and Ad26-TBS, could shorten therapy in mice. Even though immunotherapy resulted in strong splenic IFN-γ responses, no effect on bacterial replication in the lungs was seen. Multiplex assay analysis of lung samples revealed the absence of cytokine augmentation such as IFN-γ, TNF-α and IL-2, suggesting that immunization failed to induce immunity in the lungs. In this model, we show that IFN-γ levels were not associated with protection against disease relapse. The results obtained from our study raise questions regarding the traits of protective TB immunity that are relevant for the development of future immunotherapeutic and post-exposure vaccination strategies.

UR - http://www.scopus.com/inward/record.url?scp=84930658030&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930658030&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0127907

DO - 10.1371/journal.pone.0127907

M3 - Article

C2 - 25996375

AN - SCOPUS:84930658030

SN - 1932-6203

VL - 10

JO - PloS one

JF - PloS one

IS - 5

M1 - e0127907

ER -

Immunogenicity without efficacy of an adenoviral tuberculosis vaccine in a stringent mouse model for immunotherapy during treatment

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this