South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease & Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Curr Opin HIV AIDS. 2018 Nov;13(6):522-527. doi: 10.1097/COH.0000000000000496.
To outline the need for a new tuberculosis (TB) vaccine; challenges for induction of vaccine-mediated protection in HIV-infected persons; and recent advances in clinical development.
HIV has a detrimental effect on T-cell function, polarization and differentiation of Mycobacterium tuberculosis (Mtb)-specific T cells, Mtb antigen presentation by dendritic cells, and leads to B-cell and antibody-response deficiencies. Previous observations of protection against TB disease in HIV-infected persons by Mycobacterium obuense suggest that an effective vaccine against HIV-related TB is feasible. Studies of inactivated mycobacterial, viral-vectored and protein subunit vaccines reported lower immune responses in HIV-infected relative to HIV-uninfected individuals, which were only partially restored with antiretroviral therapy. Bacille Calmette Guerin (BCG) revaccination of HIV-uninfected adolescents recently showed moderate efficacy against sustained Mtb infection, but live mycobacterial vaccines have an unfavorable risk profile for HIV-infected persons. Ongoing trials of inactivated mycobacterial and protein-subunit vaccines in HIV-uninfected, Mtb-infected adults may be more relevant for protection of HIV-infected populations in TB endemic countries.
New TB vaccine candidates have potential to protect against HIV-related TB, through vaccination prior to or after HIV acquisition, but this potential may only be realized after efficacy is demonstrated in HIV-uninfected populations, with or without Mtb infection.
概述对新型结核病 (TB) 疫苗的需求;在 HIV 感染者中诱导疫苗介导的保护的挑战;以及临床开发的最新进展。
HIV 对 T 细胞功能、结核分枝杆菌 (Mtb) 特异性 T 细胞的极化和分化、树突状细胞呈递 Mtb 抗原以及导致 B 细胞和抗体反应缺陷有不利影响。先前观察到 HIV 感染者中感染分枝杆菌 obuense 可预防 TB 疾病,这表明针对与 HIV 相关的 TB 的有效疫苗是可行的。研究表明,灭活分枝杆菌、病毒载体和蛋白亚单位疫苗在 HIV 感染者中的免疫反应低于 HIV 未感染者,而抗逆转录病毒疗法仅部分恢复了这种反应。最近对 HIV 未感染者青少年进行的卡介苗复种显示对持续 Mtb 感染具有中等疗效,但活分枝杆菌疫苗对 HIV 感染者的风险状况不利。目前正在对 HIV 未感染者和 Mtb 感染者进行的灭活分枝杆菌和蛋白亚单位疫苗的临床试验,可能更适合保护结核病流行国家的 HIV 感染者人群。
新型 TB 疫苗候选物有可能通过在 HIV 感染之前或之后进行疫苗接种来预防与 HIV 相关的 TB,但只有在 HIV 未感染者中证明有效性后,无论是否存在 Mtb 感染,这种潜力才有可能实现。