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Dose Optimization of H56:IC31 Vaccine for Tuberculosis-Endemic Populations. A Double-Blind, Placebo-controlled, Dose-Selection Trial
- Source :
- American Journal of Respiratory and Critical Care Medicine. 199:220-231
- Publication Year :
- 2019
- Publisher :
- American Thoracic Society, 2019.
-
Abstract
- Global tuberculosis (TB) control requires effective vaccines in TB-endemic countries, where most adults are infected with Mycobacterium tuberculosis (M.tb).We sought to define optimal dose and schedule of H56:IC31, an experimental TB vaccine comprising Ag85B, ESAT-6, and Rv2660c, for M.tb-infected and M.tb-uninfected adults.We enrolled 98 healthy, HIV-uninfected, bacillus Calmette-Guérin-vaccinated, South African adults. M.tb infection was defined by QuantiFERON-TB (QFT) assay. QFT-negative participants received two vaccinations of different concentrations of H56 in 500 nmol of IC31 to enable dose selection for further vaccine development. Subsequently, QFT-positive and QFT-negative participants were randomized to receive two or three vaccinations to compare potential schedules. Participants were followed for safety and immunogenicity for 292 days.H56:IC31 showed acceptable reactogenicity profiles irrespective of dose, number of vaccinations, or M.tb infection. No vaccine-related severe or serious adverse events were observed. The three H56 concentrations tested induced equivalent frequencies and functional profiles of antigen-specific CD4 T cells. ESAT-6 was only immunogenic in QFT-negative participants who received three vaccinations.Two or three H56:IC31 vaccinations at the lowest dose induced durable antigen-specific CD4 T-cell responses with acceptable safety and tolerability profiles in M.tb-infected and M.tb-uninfected adults. Additional studies should validate applicability of vaccine doses and regimens to both QFT-positive and QFT-negative individuals. Clinical trial registered with www.clinicaltrials.gov (NCT01865487).
- Subjects :
- Adult
Male
Pulmonary and Respiratory Medicine
medicine.medical_specialty
Tuberculosis
Adolescent
Critical Care and Intensive Care Medicine
Placebo
Double blind
Mycobacterium tuberculosis
South Africa
Young Adult
03 medical and health sciences
0302 clinical medicine
Bacterial Proteins
Double-Blind Method
Internal medicine
medicine
Humans
030212 general & internal medicine
Tuberculosis Vaccines
Antigens, Bacterial
Dose-Response Relationship, Drug
biology
business.industry
Middle Aged
biology.organism_classification
medicine.disease
Clinical trial
Drug Combinations
Treatment Outcome
Oligodeoxyribonucleotides
030228 respiratory system
Dose optimization
Female
business
Oligopeptides
Acyltransferases
Dose selection
Subjects
Details
- ISSN :
- 15354970 and 1073449X
- Volume :
- 199
- Database :
- OpenAIRE
- Journal :
- American Journal of Respiratory and Critical Care Medicine
- Accession number :
- edsair.doi.dedup.....db667cfaad31d5da81491944c48fd269