Spatiotemporal control of immune responses with nucleic acid cocktail vaccine

Nucleic acid vaccines play important roles in prevention and treatment of diseases. However, limited immunogenicity remains a major obstacle for DNA vaccine applications in the clinic. To address the issue, the present study investigates a cocktail approach to DNA vaccination. In this proof-of-the-concept study, the cocktail consists of two DNAs encoding viral hemagglutinin (HA) and granulocyte-macrophage colony stimulatory factor (GM-CSF), respectively. Data from the study demonstrate that recruitment and activation of antigen-presenting cells (APCs) can be substantially improved by spatiotemporal regulation of GM-CSF and HA expressions at the site of vaccination. The types of recruited APCs and their phenotypes are also controllable by adjusting the cocktail compositions. Compared to mono-ingredient vaccine, the optimized cocktail vaccine is able to enhance the anti-viral humoral and T cell immune responses. No significant systemic inflammation has been detected after either prime or boost immunization using the cocktail vaccine. Data in the study suggest that the DNA cocktail is a safe, effective, and controllable platform for improving vaccine efficacy.