Penn-Nicholson Adam, Geldenhuys Hennie, Burny Wivine, van der Most Robbert, Day Cheryl L, Jongert Erik, Moris Philippe, Hatherill Mark, Ofori-Anyinam Opokua, Hanekom Willem, Bollaerts Anne, Demoitie Marie-Ange, Kany Luabeya Angelique Kany, De Ruymaeker Evi, Tameris Michele, Lapierre Didier, Scriba Thomas J
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine & Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
Vaccine. 2015 Jul 31;33(32):4025-34. doi: 10.1016/j.vaccine.2015.05.088. Epub 2015 Jun 10.
Vaccination that prevents tuberculosis (TB) disease, particularly in adolescents, would have the greatest impact on the global TB epidemic. Safety, reactogenicity and immunogenicity of the vaccine candidate M72/AS01E was evaluated in healthy, HIV-negative adolescents in a TB endemic region, regardless of Mycobacterium tuberculosis (M.tb) infection status.
In a phase II, double-blind randomized, controlled study (NCT00950612), two doses of M72/AS01E or placebo were administered intramuscularly, one month apart. Participants were followed-up post-vaccination, for 6 months. M72-specific immunogenicity was evaluated by intracellular cytokine staining analysis of T cells and NK cells by flow cytometry.
No serious adverse events were recorded. M72/AS01E induced robust T cell and antibody responses, including antigen-dependent NK cell IFN-γ production. CD4 and CD8 T cell responses were sustained at 6 months post vaccination. Irrespective of M.tb infection status, vaccination induced a high frequency of M72-specific CD4 T cells expressing multiple combinations of Th1 cytokines, and low level IL-17. We observed rapid boosting of immune responses in M.tb-infected participants, suggesting natural infection acts as a prime to vaccination.
The clinically acceptable safety and immunogenicity profile of M72/AS01E in adolescents living in an area with high TB burden support the move to efficacy trials.
预防结核病（TB）的疫苗接种，尤其是在青少年中，将对全球结核病流行产生最大影响。在结核病流行地区，对健康、HIV阴性的青少年，无论其结核分枝杆菌（M.tb）感染状况如何，评估候选疫苗M72/AS01E的安全性、反应原性和免疫原性。
在一项II期双盲随机对照研究（NCT00950612）中，肌肉注射两剂M72/AS01E或安慰剂，间隔1个月。接种疫苗后对参与者进行6个月的随访。通过流式细胞术对T细胞和NK细胞进行细胞内细胞因子染色分析，评估M72特异性免疫原性。
未记录到严重不良事件。M72/AS01E诱导了强烈的T细胞和抗体反应，包括抗原依赖性NK细胞产生IFN-γ。接种疫苗后6个月，CD4和CD8 T细胞反应持续存在。无论M.tb感染状况如何，接种疫苗均诱导了高频率表达多种Th1细胞因子组合的M72特异性CD4 T细胞，以及低水平的IL-17。我们观察到M.tb感染参与者的免疫反应迅速增强，表明自然感染可作为疫苗接种的初免。
M72/AS01E在结核病负担高的地区青少年中具有临床可接受的安全性和免疫原性，支持开展疗效试验。
