Abstract
The development of a vaccine against tuberculosis (TB), a disease caused by Mycobacterium tuberculosis, is urgently needed. The only currently available vaccine, M. bovis BCG, has variable efficacy. One approach in the global vaccine development effort is focused on boosting BCG using subunit vaccines. The identification of novel antigens for inclusion in subunit vaccines is a critical step in the TB vaccine development pathway. We selected four novel mycobacterial antigens recognized during the course of human infection. A replication-deficient chimpanzee adenovirus (ChAdOx1) was constructed to express each antigen individually, and these vectors were evaluated for protective efficacy in murine M. tuberculosis challenge experiments. One antigen, PPE15 (Rv1039c), conferred significant and reproducible protection when administered alone and as a boost to BCG vaccination. We identified immunodominant epitopes to define the protective immune responses using tetramers and intravascular staining. Lung parenchymal CD4+ and CD8+ CXCR3+ KLRG1- T cells, previously associated with protection against M. tuberculosis, were enriched in the vaccinated groups compared to the control groups. Further work to evaluate the protective efficacy of PPE15 in more stringent preclinical animal models, together with the identification of further novel protective antigens using this selection strategy, is now merited.
| Original language | English (US) |
|---|---|
| Article number | e00014-18 |
| Journal | Infection and Immunity |
| Volume | 86 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1 2018 |
Fingerprint
Keywords
- Mycobacterium tuberculosis
- Tuberculosis
- Vaccines
- Viral vectors
ASJC Scopus subject areas
- Parasitology
- Microbiology
- Immunology
- Infectious Diseases
Cite this
Identification and evaluation of novel protective antigens for the development of a candidate tuberculosis subunit vaccine. / Stylianou, Elena; Harrington-Kandt, Rachel; Beglov, Julia; Bull, Naomi; Pinpathomrat, Nawamin; Swarbrick, Gwendolyn M.; Lewinsohn, Deborah; Lewinsohn, David; McShane, Helen.
In: Infection and Immunity, Vol. 86, No. 7, e00014-18, 01.07.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Identification and evaluation of novel protective antigens for the development of a candidate tuberculosis subunit vaccine
AU - Stylianou, Elena
AU - Harrington-Kandt, Rachel
AU - Beglov, Julia
AU - Bull, Naomi
AU - Pinpathomrat, Nawamin
AU - Swarbrick, Gwendolyn M.
AU - Lewinsohn, Deborah
AU - Lewinsohn, David
AU - McShane, Helen
PY - 2018/7/1
Y1 - 2018/7/1
N2 - The development of a vaccine against tuberculosis (TB), a disease caused by Mycobacterium tuberculosis, is urgently needed. The only currently available vaccine, M. bovis BCG, has variable efficacy. One approach in the global vaccine development effort is focused on boosting BCG using subunit vaccines. The identification of novel antigens for inclusion in subunit vaccines is a critical step in the TB vaccine development pathway. We selected four novel mycobacterial antigens recognized during the course of human infection. A replication-deficient chimpanzee adenovirus (ChAdOx1) was constructed to express each antigen individually, and these vectors were evaluated for protective efficacy in murine M. tuberculosis challenge experiments. One antigen, PPE15 (Rv1039c), conferred significant and reproducible protection when administered alone and as a boost to BCG vaccination. We identified immunodominant epitopes to define the protective immune responses using tetramers and intravascular staining. Lung parenchymal CD4+ and CD8+ CXCR3+ KLRG1- T cells, previously associated with protection against M. tuberculosis, were enriched in the vaccinated groups compared to the control groups. Further work to evaluate the protective efficacy of PPE15 in more stringent preclinical animal models, together with the identification of further novel protective antigens using this selection strategy, is now merited.
AB - The development of a vaccine against tuberculosis (TB), a disease caused by Mycobacterium tuberculosis, is urgently needed. The only currently available vaccine, M. bovis BCG, has variable efficacy. One approach in the global vaccine development effort is focused on boosting BCG using subunit vaccines. The identification of novel antigens for inclusion in subunit vaccines is a critical step in the TB vaccine development pathway. We selected four novel mycobacterial antigens recognized during the course of human infection. A replication-deficient chimpanzee adenovirus (ChAdOx1) was constructed to express each antigen individually, and these vectors were evaluated for protective efficacy in murine M. tuberculosis challenge experiments. One antigen, PPE15 (Rv1039c), conferred significant and reproducible protection when administered alone and as a boost to BCG vaccination. We identified immunodominant epitopes to define the protective immune responses using tetramers and intravascular staining. Lung parenchymal CD4+ and CD8+ CXCR3+ KLRG1- T cells, previously associated with protection against M. tuberculosis, were enriched in the vaccinated groups compared to the control groups. Further work to evaluate the protective efficacy of PPE15 in more stringent preclinical animal models, together with the identification of further novel protective antigens using this selection strategy, is now merited.
KW - Mycobacterium tuberculosis
KW - Tuberculosis
KW - Vaccines
KW - Viral vectors
UR - http://www.scopus.com/inward/record.url?scp=85050107942&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85050107942&partnerID=8YFLogxK
U2 - 10.1128/IAI.00014-18
DO - 10.1128/IAI.00014-18
M3 - Article
C2 - 29661928
AN - SCOPUS:85050107942
VL - 86
JO - Infection and Immunity
JF - Infection and Immunity
SN - 0019-9567
IS - 7
M1 - e00014-18
ER -