title: Non-clinical efficacy and safety of HyVac4:IC31 vaccine administered in a BCG prime-boost regimen.
abstract: Despite the extensive success with the introduction of M. bovis Bacille Calmette-Guérin (BCG), tuberculosis (TB) remains a major global epidemic infecting between 8 and 9 million people annually with an estimated 1.7 million deaths each year. However, because of its demonstrated effectiveness against some of the most severe forms of childhood TB, it is now realized that BCG vaccination of newborns is unlikely to be replaced. Therefore, BCG or an improved BCG will continue to be used as a prime TB vaccine and there is a need to develop effective boost vaccines that would enhance and prolong the protective immunity induced by BCG prime immunization. We report on a heterologous booster approach using two highly immunogenic TB antigens comprising Ag85B and TB10.4 (HyVac4) delivered as a fusion molecule and formulated in the proprietary adjuvant IC31. This vaccine was found to be immunogenic and demonstrated greater protection in the more stringent guinea pig model of pulmonary tuberculosis than BCG alone when used in a prime/boost regimen. Significant difference in lung involvement was observed for all animals in the HyVac4 boosted group compared to BCG alone regardless of time to death or sacrifice. A vaccine toxicology study of the HyVac4:IC31 regimen was performed and it was judged safe to advance the vaccine into clinical trials. Therefore, all non-clinical data supports the suitability of HyVac4 as a safe, immunogenic, and effective vaccination in a prime-boost regimen with BCG.
authors.affiliation: Aeras Global TB Vaccine Foundation, Rockville, MD 20850, USA. yskeiky@aeras.org
authors.forename: Yasir A W
authors.initials: YA
authors.lastname: Skeiky
authors.forename: Jes
authors.initials: J
authors.lastname: Dietrich
authors.forename: Todd M
authors.initials: TM
authors.lastname: Lasco
authors.forename: Katherine
authors.initials: K
authors.lastname: Stagliano
authors.forename: Veerabadran
authors.initials: V
authors.lastname: Dheenadhayalan
authors.forename: Margaret Ann
authors.initials: MA
authors.lastname: Goetz
authors.forename: Luis
authors.initials: L
authors.lastname: Cantarero
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Basaraba
authors.forename: Peter
authors.initials: P
authors.lastname: Bang
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kromann
authors.forename: J Bruce
authors.initials: JB
authors.lastname: McMclain
authors.forename: Jerald C
authors.initials: JC
authors.lastname: Sadoff
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D004338:Drug Combinations; D005260:Female; D006168:Guinea Pigs; D007117:Immunization, Secondary / Q000379:methods*; D008168:Lung / Q000276:immunology / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000009:adverse effects*; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D016019:Survival Analysis; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000517:prevention & control*; D014611:Vaccination / Q000379:methods*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D004338:Drug Combinations; C544002:IC31 adjuvant; D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; D014614:Vaccines, Synthetic