Weilhammer Dina, Dunkle Alexis D, Blanchette Craig D, Fischer Nicholas O, Corzett Michele, Lehmann Doerte, Boone Tyler, Hoeprich Paul, Driks Adam, Rasley Amy
Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, United States.
Department of Microbiology & Immunology, Loyola University Medical Center, United States.
Vaccine. 2017 Mar 13;35(11):1475-1481. doi: 10.1016/j.vaccine.2017.02.004. Epub 2017 Feb 14.
To address the need for vaccine platforms that induce robust cell-mediated immunity, we investigated the potential of utilizing self-assembling biologic nanolipoprotein particles (NLPs) as an antigen and adjuvant delivery system to induce antigen-specific murine T cell responses. We utilized OT-I and OT-II TCR-transgenic mice to investigate the effects of NLP-mediated delivery of the model antigen ovalbumin (OVA) on T cell activation. Delivery of OVA with the TLR4 agonist monophosphoryl lipid A (MPLA) in the context of NLPs significantly enhanced the activation of both CD4 and CD8 T cells in vitro compared to co-administration of free OVA and MPLA. Upon intranasal immunization of mice harboring TCR-transgenic cells, NLPs enhanced the adjuvant effects of MPLA and the in vivo delivery of OVA, leading to significantly increased expansion of CD4 and CD8 T cells in lung-draining lymph nodes. Therefore, NLPs are a promising vaccine platform for inducing T cell responses following intranasal administration.
为满足对能诱导强大细胞介导免疫的疫苗平台的需求,我们研究了利用自组装生物纳米脂蛋白颗粒(NLP)作为抗原和佐剂递送系统来诱导抗原特异性小鼠T细胞反应的潜力。我们利用OT-I和OT-II TCR转基因小鼠来研究NLP介导递送模型抗原卵清蛋白(OVA)对T细胞活化的影响。与游离OVA和单磷酰脂质A(MPLA)共同给药相比,在NLP的背景下将OVA与TLR4激动剂MPLA一起递送,在体外显著增强了CD4和CD8 T细胞的活化。对携带TCR转基因细胞的小鼠进行鼻内免疫后,NLP增强了MPLA的佐剂作用以及OVA的体内递送,导致肺引流淋巴结中CD4和CD8 T细胞的扩增显著增加。因此,NLP是一种有前景的疫苗平台,可在鼻内给药后诱导T细胞反应。