RESUMO
RATIONALE: Administration of tuberculosis (TB) vaccines in participants with previous or current pulmonary TB may have the potential for causing harmful postvaccination immunologic (Koch-type) reactions. OBJECTIVES: To assess the safety and immunogenicity of three dose levels of the AERAS-402 live, replication-deficient adenovirus 35-vectored TB candidate vaccine, containing three mycobacterial antigens, in individuals with current or previous pulmonary TB. METHODS: We performed a phase II randomized, placebo-controlled, double-blinded dose-escalation study in an HIV-negative adult South African cohort (n = 72) with active pulmonary TB (on treatment for 1-4 mo) or pulmonary TB treated at least 12 months before study entry and considered cured. Safety endpoints included clinical assessment, flow volume curves, diffusing capacity of the lung for carbon monoxide, pulse oximetry, chest radiograph, and high-resolution thoracic computerized tomography scans. Cytokine expression by CD4 and CD8 T cells, after stimulation with Ag85A, Ag85B, and TB10.4 peptide pools, was examined by intracellular cytokine staining. MEASUREMENTS AND MAIN RESULTS: No apparent temporal or dose-related changes in clinical status (specifically acute, Koch phenomenon-like reactions), lung function, or radiology attributable to vaccine were observed. Injection site reactions were mild or moderate. Hematuria (by dipstick only) occurred in 25 (41%) of 61 AERAS-402 recipients and 3 (27%) of 11 placebo recipients, although no gross hematuria was reported. AERAS-402 induced robust CD8+ and moderate CD4+ T-cell responses, mainly to Ag85B in both vaccine groups. CONCLUSIONS: Administration of the AERAS-402 candidate TB vaccine to participants with current or previous pulmonary TB induced a robust immune response and is not associated with clinically significant pulmonary complications. Clinical trial registered with www.clinicaltrials.gov (NCT 02414828) and in the South African National Clinical Trials Register ( www.sanctr.gov.za DOH 27-0808-2060).
Assuntos
Vacinas contra a Tuberculose/uso terapêutico , Tuberculose Pulmonar/terapia , Adenoviridae , Adulto , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Pulmão/diagnóstico por imagem , Medidas de Volume Pulmonar , Masculino , Pessoa de Meia-Idade , Oximetria , Radiografia Torácica , Tomografia Computadorizada por Raios X , Vacinas contra a Tuberculose/administração & dosagem , Vacinas contra a Tuberculose/efeitos adversos , Vacinas contra a Tuberculose/imunologia , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/imunologia , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/uso terapêutico , Vacinas de DNA , Vacinas Sintéticas , Adulto JovemAssuntos
Linfócitos T CD8-Positivos/imunologia , Citometria de Fluxo/métodos , Mycobacterium tuberculosis/imunologia , Células Th1/imunologia , Células Th2/imunologia , Antígenos de Bactérias/imunologia , Ligante de CD40/imunologia , Fluoresceína-5-Isotiocianato , Humanos , Memória Imunológica/imunologia , Interferon gama/imunologia , Interleucina-2/imunologia , Interleucina-4/imunologia , Interleucinas/imunologia , Proteína 1 de Membrana Associada ao Lisossomo/imunologia , Tuberculose Pulmonar/imunologia , Fator de Necrose Tumoral alfa/imunologia , Interleucina 22RESUMO
Transcatheter coil embolization is an established treatment for pulmonary arteriovenous malformations (PAVMs). Encountering a patient with a symptomatic PAVM partially occluded with a prominent clot is rare. Successful and safe coil embolization of such a PAVM is described in this case report.