Karaliota Sevasti, Moussa Maha, Rosati Margherita, Devasundaram Santhi, Sengupta Soumya, Goldfarbmuren Katherine C, Burns Robert, Bear Jenifer, Stellas Dimitris, Urban Elizabeth A, Deleage Claire, Khandhar Amit P, Erasmus Jesse, Berglund Peter, Reed Steven G, Pavlakis George N, Felber Barbara K
Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
Basic Science Program, Leidos Biomedical Research, Inc., Frederick, MD, USA.
iScience. 2025 Mar 18;28(4):112232. doi: 10.1016/j.isci.2025.112232. eCollection 2025 Apr 18.
A SARS-CoV-2 spike DNA vaccine formulated with a cationic nanoparticle emulsion (LION) was tested in Rhesus macaques. It induced robust, long-lasting (>2 years) cellular and humoral immunity, including increased neutralization breadth. T cell responses were predominantly CD8, in contrast to other DNA vaccines. A rapid transient cytokine/chemokine response was associated with expansion and trafficking of myeloid cells and lymphocytes. Increased proliferation and dynamic changes between blood and lymph node (LN) were found for monocyte-derived cells, dendritic cells, and B and T cells, resulting in activation of LN and expansion of germinal centers (GCs), likely critical in shaping long-lasting adaptive immunity. Significant GC expansion of B, CD4-, and CD8- cells, including the Tfc3 subset, reflects a balanced immune response, including antibody (Ab) development. DNA/LION vaccination activates myeloid and lymphoid cells in blood and LN and promotes effective antigen presentation, resulting in sustained antigen-specific cellular and humoral responses, emerging as an effective DNA vaccine delivery platform.
一种用阳离子纳米颗粒乳剂（LION）配制的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突DNA疫苗在恒河猴身上进行了测试。它诱导了强大、持久（>2年）的细胞免疫和体液免疫，包括中和广度增加。与其他DNA疫苗相比，T细胞反应主要是CD8反应。快速短暂的细胞因子/趋化因子反应与髓样细胞和淋巴细胞的扩增及迁移有关。单核细胞衍生细胞、树突状细胞以及B细胞和T细胞在血液和淋巴结（LN）之间的增殖增加和动态变化，导致LN激活和生发中心（GC）扩大，这可能对形成持久的适应性免疫至关重要。B细胞、CD4+细胞和CD8+细胞（包括Tfc3亚群）的显著GC扩大反映了包括抗体（Ab）产生在内的平衡免疫反应。DNA/LION疫苗接种激活血液和LN中的髓样细胞和淋巴细胞，并促进有效的抗原呈递，从而产生持续的抗原特异性细胞免疫和体液免疫反应，成为一种有效的DNA疫苗递送平台。
