Tameris Michele, Geldenhuys Hennie, Luabeya Angelique KanyKany, Smit Erica, Hughes Jane E, Vermaak Samantha, Hanekom Willem A, Hatherill Mark, Mahomed Hassan, McShane Helen, Scriba Thomas J
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
Jenner Institute, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
PLoS One. 2014 Feb 3;9(2):e87340. doi: 10.1371/journal.pone.0087340. eCollection 2014.
Vaccination against tuberculosis (TB) should provide long-term protective immunity against Mycobacterium tuberculosis (M.tb). The current TB vaccine, Bacille Calmette-Guerin (BCG), protects against disseminated childhood TB, but protection against lung TB in adolescents and adults is variable and mostly poor. One potential reason for the limited durability of protection may be waning of immunity through gradual attrition of BCG-induced T cells. We determined if a MVA85A viral-vector boost could enhance the durability of mycobacteria-specific T cell responses above those induced by BCG alone.
We describe a long-term follow-up study of persons previously vaccinated with MVA85A. We performed a medical history and clinical examination, a tuberculin skin test and measured vaccine-specific T cell responses in persons previously enrolled as adults, adolescents, children or infants into three different Phase II trials, between 2005 and 2011.
Of 252 potential participants, 183 (72.6%) consented and completed the study visit. Vaccine-induced Ag85A-specific CD4+ T cell responses were remarkably persistent in healthy, HIV-uninfected adults, adolescents, children and infants, up to 6 years after MVA85A vaccination. Specific CD4+ T cells expressed surface markers consistent with either CD45RA-CCR7+ central memory or CD45RA-CCR7- effector memory T cells. Similarly durable Ag85A-specific CD4+ T cell responses were detected in HIV-infected persons who were on successful antiretroviral therapy when MVA85A was administered. By contrast, Ag85A-specific CD4+ T cell frequencies in untreated MVA85A-vaccinated HIV-infected persons were mostly undetectable 3-5 years after vaccination.
MVA85A induces remarkably durable T cell responses in immunocompetent persons. However, results from a recent phase IIb trial of MVA85A, conducted in infants from the same geographic area and study population, showed no vaccine efficacy, suggesting that these durable T cell responses do not enhance BCG-induced protection against TB in infants.
结核病（TB）疫苗接种应能提供针对结核分枝杆菌（M.tb）的长期保护性免疫。目前的结核病疫苗卡介苗（BCG）可预防儿童播散性结核病，但对青少年和成人肺结核的保护作用不一且大多较差。保护作用持久性有限的一个潜在原因可能是卡介苗诱导的T细胞逐渐损耗导致免疫力下降。我们确定了MVA85A病毒载体加强免疫是否能增强分枝杆菌特异性T细胞反应的持久性，使其高于单独卡介苗诱导的反应。
我们描述了一项对先前接种MVA85A的人群进行的长期随访研究。我们对2005年至2011年间分别作为成人、青少年、儿童或婴儿纳入三项不同II期试验的人群进行了病史和临床检查、结核菌素皮肤试验，并测量了疫苗特异性T细胞反应。
在252名潜在参与者中，183名（72.6%）同意并完成了研究访视。在健康、未感染HIV的成人、青少年、儿童和婴儿中，疫苗诱导的Ag85A特异性CD4+T细胞反应在MVA85A接种后长达6年都非常持久。特异性CD4+T细胞表达的表面标志物与CD45RA-CCR7+中央记忆T细胞或CD45RA-CCR7-效应记忆T细胞一致。在接种MVA85A时接受成功抗逆转录病毒治疗的HIV感染者中也检测到了同样持久的Ag85A特异性CD4+T细胞反应。相比之下，未治疗的接种MVA85A的HIV感染者在接种后3至5年大多检测不到Ag85A特异性CD4+T细胞频率。
MVA85A在免疫功能正常的人群中诱导出非常持久的T细胞反应。然而，最近在同一地理区域和研究人群的婴儿中进行的MVA85A IIb期试验结果显示没有疫苗效力，这表明这些持久的T细胞反应并不能增强卡介苗对婴儿结核病的诱导保护作用。
