Highly immunogenic DNA/LION nanocarrier vaccine potently activates lymph nodes inducing long-lasting immunity in macaques.

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.