Novel highly immunogenic DNA vaccine regimen potently activates lymph nodes in macaques.

Background

We evaluated a novel DNA vaccine delivery by LION™ nanoparticles for its ability to induce innate and adaptive immune responses in Rhesus macaques. 

Methods

CoV-2 Spike or HIV Env DNA were formulated with a cationic nanocarrier (Lipid InOrganic Nanoparticle; LION™) administered via the IM route. Chemokine/cytokine and vaccine-specific responses were monitored in blood and lymph nodes (LN) by proteomics, flow, antibody assays.

Results

DNA/LION™ induced strong cellular and higher humoral responses than DNA/Electroporation and induced rapid (4-24hr) transient innate responses. Flow analysis showed activation of T, B, myeloid incl. dendritic cells in blood and their trafficking to LN with a strong increase of Tfh, Germinal Center Tfh CD4 and CD8 cells. Cell subsets were activated by cytokine networks incl. CXCL11, IL-7 and IL-15. GC-B cell activation directly correlated with increase of FLT3L and CXCL12 and importantly with antibody levels. 

Conclusion

DNA/LION™ led to robust induction of cellular and humoral responses against different immunogens, serving as promising platform of effective nucleic acid vaccine delivery.  Transient cytokine responses, incl. IL-15, resulted in strong activation of draining lymph nodes, and contributed to shaping adaptive (cellular and humoral) immunity. Our data showed rapid and coordinated cytokine responses to the vaccine and highlight the important role of innate responses to vaccination in modulating adaptive immunity.