Grover Ajay, McLean Jennifer L, Troudt JoLynn M, Foster Chad, Izzo Linda, Creissen Elisabeth, MacDonald Elisabeth, Troy Amber, Izzo Angelo A
Colorado State University, Department of Microbiology, Immunology & Pathology, Fort Collins, CO 80523, USA.
Colorado State University, Department of Microbiology, Immunology & Pathology, Fort Collins, CO 80523, USA.
Vaccine. 2016 May 27;34(25):2798-805. doi: 10.1016/j.vaccine.2016.04.052. Epub 2016 Apr 28.
The use of novel vaccine delivery systems allows for the manipulation of the adaptive immune systems through the use of molecular adjuvants that target specific innate pathways. Such strategies have been used extensively for vaccines against cancer and multiple pathogens such as Mycobacterium tuberculosis. In the current study we used heat killed non-pathogenic recombinant Saccharomyces cerevisiae expressing M. tuberculosis antigen Rv1886c (fbpB, mpt59, Ag85B) as a delivery system in conjunction with its ability to stimulate innate immunity to determine its ability to induce immunity. We established that the recombinant yeast induced activated antigen specific T cells are capable of reducing the mycobacterial burden. Inoculation of the recombinant yeast after vaccination with BCG resulted in a systemic alteration of the phenotype of the immune response although this was not reflected in an increase in the reduction of the mycobacterial burden. Taken together the data suggest that heat killed yeast can induce multiple cytokines required for induction of protective immunity and can function as a vehicle for delivery of M. tuberculosis antigens in a vaccine formulation. In addition, while it can enhance the effector memory response induced by BCG, it had little effect on central memory responses.
新型疫苗递送系统的使用能够通过靶向特定固有途径的分子佐剂来调控适应性免疫系统。此类策略已广泛应用于癌症疫苗以及针对多种病原体(如结核分枝杆菌)的疫苗。在本研究中,我们使用表达结核分枝杆菌抗原Rv1886c(fbpB、mpt59、Ag85B)的热灭活非致病性重组酿酒酵母作为递送系统,并结合其刺激固有免疫的能力来确定其诱导免疫的能力。我们证实,重组酵母诱导的活化抗原特异性T细胞能够减轻分枝杆菌负荷。在接种卡介苗后接种重组酵母导致免疫反应表型的全身性改变,尽管这并未表现为分枝杆菌负荷降低的增加。综合来看,数据表明热灭活酵母能够诱导保护性免疫所需的多种细胞因子,并且在疫苗制剂中可作为结核分枝杆菌抗原的递送载体。此外,虽然它可以增强卡介苗诱导的效应记忆反应,但对中枢记忆反应影响很小。