Red blood cells, or erythrocytes, play important innate immune functions, including the capture and delivery of bacterial pathogens to the antigen presenting cells (APCs) in the spleen.
The researchers harnessed erythrocyte immune functions to develop Erythrocyte Driven Immune Targeting (EDIT), a method to deliver vaccine nanoparticles from the surface of red blood cells to the APCs in the spleen and generate cellular and humoral immune responses.
At an incubation ratio of 300:1 (nanoparticles: erythrocytes), nanoparticle loading per erythrocyte was found to be optimal for developing enough shear resistance to ensure that the nanoparticles were mostly delivered to the spleen rather than the lungs.
Once the nanoparticles reached the spleen, alterations to the erythrocyte membrane led to their prompt capture by spleen APCs, without the capture of the carrier cell. EDIT led to improved humoral and cellular immune responses, with the erythrocyte-delivered nanoparticles resulting in higher antibody response, higher central memory T cell response, and lower regulatory T cells, compared with free nanoparticles.
In a mouse model of prophylaxis, EDIT-mediated immune responses were found to significantly slow tumor growth and increase the window for therapeutic interventions.
According to the authors, EDIT could be used for erythrocyte-mediated delivery of antigens to stimulate enhanced systemic immunity and serve as the basis for vaccination strategies.
https://www.pnas.org/content/early/2020/07/13/2002880117
Using red blood cells to deliver vaccine to spleen
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