Discovery in 2007 of a prototype tuberculosis vaccine based on Ad35 intended to be used both in children and adults who either received or did not receive BCG (Radosevic, Infect Immun, 2007). A first hint of a correlate of protection was found. Subsequently in clinical trials it was shown that
this TB vaccine was well tolerated in newborns and induced a significant T cell response. In addition it was shown that in HIV seropositive individuals vaccination results in impressive responses, opening the road for therapeutic TB vaccination with the goal of shortening antibiotic treatment. Currently efficacy trials in BCG primed children and HIV infected individuals are underway. Combining rBCG with the TB Ad35 vaccine improves protective responses (Magalhaes, PLOS One, 2008) and applying the vaccine directly to the respiratory system via inhalation improves the effect of the vaccine (Jin, Vaccine 2010 ; Song, PNAS 2010)
RADOSEVIC, K., WIELAND, C.W., RODRIGUEZ, A., WEVERLING, G.J.,
MINTARDJO, R., GILLISSEN, G., VOGELS, R., SKEIKY, Y.A., HONE, D.M., SADOFF, J., POLL, T. VAN DER, HAVENGA, M., and GOUDSMIT, J. (2007)
Protective immune responses to a recombinant adenovirus type 35 tuberculosis vaccine in two mouse strains: CD4 and CD8 T-cell epitope mapping and role of gamma interferon.
Infect Immun 75 (8): 4105-4115.
PubMed publication date: Aug 2007.
PubMed link to abstract: http://www.ncbi.nlm.nih.gov/pubmed/17526747
PDF: Infect Immun_2007_75_8_4105_Radosevic
MAGALHAES, I., SIZEMORE, D.R., AHMED, R.K., MUELLER, S., WEHLIN, L.,
SCANGA, C., WEICHOLD, F., SCHIRRU, G., PAU, M.G., GOUDSMIT, J.,
KUHLMANN-BERENZON, S., SPANGBERG, M., ANDERSSON, J., GAINES, H., THORSTENSSON, R., SKEIKY, Y.A., SADOFF, J., and MAEURER, M. (2008)
rBCG induces strong antigen-specific T cell responses in rhesus macaques in a
prime-boost setting with an adenovirus 35 tuberculosis vaccine vector.
PLoS ONE 3 (11): e3790.
PubMed publication date: Nov 21, 2008.
PubMed link to abstract: http://www.ncbi.nlm.nih.gov/pubmed/19023426
PDF: PLoS ONE_2008_3_11_e3790_Magalhaes
JIN, T.H., TSAO, E., GOUDSMIT, J., DHEENADHAYALAN, V., and SADOFF, J. (2010)
Stabilizing formulations for inhalable powders of an adenovirus 35-vectored tuberculosis (TB) vaccine (AERAS-402).
Vaccine 28 (27): 4369-4375.
PubMed publication date: Jun 17, 2010.
PubMed link to abstract: http://www.ncbi.nlm.nih.gov/pubmed/20444437
SONG, K., BOLTON, D.L., WILSON, R.L., CAMP, J.V., BAO, S., MATTAPALLIL, J.J., HERZENBERG, L.A., ANDREWS, C.A., SADOFF, J.C., GOUDSMIT, J., PAU, M.G., SEDER, R.A., KOZLOWSKI, P.A., NABEL, G.J., ROEDERER, M., and RAO, S.S. (2010)
Genetic immunization in the lung induces potent local and systemic immune responses.
Proc Natl Acad Sci U S A 107 (51): 22213-22218.
PubMed publication date: Dec 21, 2010.
PubMed link to abstract: http://www.ncbi.nlm.nih.gov/pubmed/21135247