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Adenovirus type 35-vectored tuberculosis vaccine has an acceptable safety and tolerability profile in healthy, BCG-vaccinated, QuantiFERON(®)-TB Gold (+) Kenyan adults without evidence of tuberculosis.
- Source :
-
Vaccine [Vaccine] 2016 May 05; Vol. 34 (21), pp. 2430-2436. Date of Electronic Publication: 2016 Mar 26. - Publication Year :
- 2016
-
Abstract
- In a Phase 1 trial, we evaluated the safety of AERAS-402, an adenovirus 35-vectored TB vaccine candidate expressing 3 Mycobacterium tuberculosis (Mtb) immunodominant antigens, in subjects with and without latent Mtb infection. HIV-negative, BCG-vaccinated Kenyan adults without evidence of tuberculosis, 10 QuantiFERON(®)-TB Gold In-Tube test (QFT-G)(-) and 10 QFT-G(+), were randomized 4:1 to receive AERAS-402 or placebo as two doses, on Days 0 and 56, with follow up to Day 182. There were no deaths, serious adverse events or withdrawals. For 1 AERAS-402 QFT-G(-) and 1 AERAS-402 QFT-G(+) subject, there were 3 self-limiting severe AEs of injection site pain: 1 after the first vaccination and 1 after each vaccination, respectively. Two additional severe AEs considered vaccine-related were reported after the first vaccination in AERAS-402 QFT-G(+) subjects: elevated blood creatine phosphokinase and neutropenia, the latter slowly improving but remaining abnormal until study end. AERAS-402 was not detected in urine or throat cultures for any subject. In intracellular cytokine staining studies, curtailed by technical issues, we saw modest CD4+ and CD8+ T cell responses to Mtb Ag85A/b peptide pools among both QFT-G(-) and (+) subjects, with trends in the CD4+ T cells suggestive of boosting after the second vaccine dose, slightly more so in QFT-G(+) subjects. CD4+ and CD8+ responses to Mtb antigen TB10.4 were minimal. Increases in Adenovirus 35 neutralizing antibodies from screening to end of study, seen in 50% of AERAS-402 recipients, were mostly minimal. This small study confirms acceptable safety and tolerability profiles for AERAS-402, in line with other Phase 1 studies of AERAS-402, now to include QFT-G(+) subjects.<br /> (Published by Elsevier Ltd.)
- Subjects :
- Acyltransferases immunology
Adult
Antibodies, Neutralizing blood
Antigens, Bacterial immunology
Bacterial Proteins immunology
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Creatine Kinase blood
Cytokines immunology
Female
Healthy Volunteers
Humans
Interferon-gamma immunology
Kenya epidemiology
Male
Middle Aged
Neutropenia etiology
Tuberculosis epidemiology
Tuberculosis prevention & control
Vaccination
Vaccines, DNA
Young Adult
Antibodies, Bacterial blood
BCG Vaccine immunology
Immunogenicity, Vaccine
Latent Tuberculosis immunology
Mycobacterium tuberculosis immunology
Tuberculosis Vaccines adverse effects
Tuberculosis Vaccines immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2518
- Volume :
- 34
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Vaccine
- Publication Type :
- Academic Journal
- Accession number :
- 27026148
- Full Text :
- https://doi.org/10.1016/j.vaccine.2016.03.069