RT Journal Article
SR Electronic
T1 Predicting vaccine efficacy against tuberculosis using immunologic and radiologic measures in the non-human primate model
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 146.20
OP 146.20
VO 196
IS 1 Supplement
A1 DiFazio, Robert M
A1 Maiello, Pauline
A1 Tomko, Jaime
A1 Frye, Lonnie
A1 Bigbee, Carolyn
A1 Chedrick, Chelsea
A1 Updike, Cassaundra
A1 Lin, Philana
A1 Agger, Else Marie
A1 Andersen, Peter
A1 Flynn, JoAnne L
YR 2016
UL http://www.jimmunol.org/content/196/1_Supplement/146.20.abstract
AB The only licensed vaccine (BCG) for tuberculosis (TB) has variable efficacy and does not protect against pulmonary TB. New vaccines are in development and in human clinical trials. However, vaccine trials are long and expensive without useful surrogate markers of protection. A problem thus emerges: what does a protective response to TB look like? This project’s goal is to identify markers of vaccine efficacy that can further be developed as new clinical endpoints. We posit that exploiting differences in vaccine outcome (protected vs. unprotected) will identify novel markers that correlate with outcome, and that serial PET/CT will predict outcome early in infection, as well as identify sites of protection. Cynomolgus macaques vaccinated with BCG and a multistage vaccine (H56 in CAF01) have more sterile thoracic lymph nodes (LN) 6 months post-Mtb challenge, compared to unvaccinated controls, indicating that LN play an important role in H56-conferred protection. BCG/H56 prevents dissemination but not establishment of infection; vaccinated animals also have fewer CFU per granuloma than controls. Total FDG avidity by PET scan in lungs (a surrogate for inflammation and disease) and individual granuloma FDG avidity of vaccinated animals are significantly lower than controls at both early and late time points. Total FDG avidity can also be used to predict vaccine efficacy, as the animals protected by BCG/H56 had less FDG in lungs than unprotected vaccinated and latent controls at early time points post challenge, and will be further developed as a surrogate marker of protection at early time points in pre-clinical trials.