Vaccines from blood
Red blood cells not only carry oxygen from the lungs to the organs, they also help the body fight infections by capturing pathogenic microorganisms on its surface, neutralizing and presenting them to immune cells in the spleen and liver. A group of researchers from the Wyss Institute and the John Paulson School of Engineering and Applied Sciences (SEAS) at Harvard University used this innate ability and created a technology for delivering antigens by erythrocytes to antigen-presenting cells in the spleen to generate an immune response. The new approach has successfully slowed the growth of tumors in mice and can also be used as a biocompatible adjuvant for various vaccines. The technology is called erythrocyte-Driven Immune Targeting (Erythrocyte-Driven Immune Targeting, EDIT).
Don't kill me, but check it out
The use of red blood cells as a means of drug delivery is not a new idea, but the vast majority of existing technologies are intended for the lungs, because passing through a dense network of capillaries in them leads to the separation of cargo from red blood cells.
The research team first needed to figure out how to attach antigens to red blood cells strongly enough that they could reach the spleen unchanged. They coated polystyrene nanoparticles with ovalbumin , the main protein of egg white, which is known to cause a weak immune response, and then incubated them with mouse red blood cells. When the ratio of nanoparticles to erythrocytes was 300:1, the largest number of nanoparticles were associated with cells. About 80% of the resulting complexes were not destroyed when exposed to the shear stress characteristic of lung capillaries, and moderately expressed phosphatidylserine molecules.
The appearance of phosphatidylserine on the outer membrane of the cell serves as an indicator of apoptosis, a high level of it in red blood cells is, in fact, a "kill me" signal for the spleen – the researchers wanted to avoid it. A small amount of phosphatidylserine, as the authors expected, instead of "kill me" will give the signal "check me" to the antigen-presenting cells of the spleen, and the latter will then take the nanoparticles with the antigen without destroying red blood cells.
To test this hypothesis, the team injected red blood cells coated with nanoparticles into mice, and then tracked in which organs they accumulated. 20 minutes after injection, more than 99% of the nanoparticles were separated from the blood cells, and more nanoparticles were present in the spleen than in the lungs. A higher accumulation of nanoparticles in the spleen persisted for up to 24 hours, and the number of EDIT-red blood cells without cargo in the bloodstream remained unchanged, that is, red blood cells successfully delivered their loads to the spleen without destruction.
Effective vaccines without adjuvants
Having shown that the nanoparticles were successfully delivered to the spleen in vivo, the researchers then assessed whether the antigens on the surface of the nanoparticles caused an immune response. Mice were injected with EDIT once a week for three weeks, and then the spleen cells were analyzed. The treated mice showed an eight-fold increase in the number of T-lymphocytes, demonstrating successful delivery of ovalbumin, compared with mice injected with "free" nanoparticles or who received no treatment. Mice treated with EDIT also produced more antibodies against ovalbumin in their blood than any other group of mice.
To see if EDIT-induced immune responses could potentially prevent or treat the disease, the team repeated a three-week prophylactic injection of EDIT to mice and then inoculated them with lymphoma cells that expressed ovalbumin. In mice after EDIT, tumor growth was about three times slower compared to the control group and the group that received free nanoparticles, and there were fewer viable cancer cells. This result significantly increased the time interval during which the tumor could be cured before the disease killed the mice.
The group continues to work on understanding exactly how the immune response to the antigen presented by EDIT is generated by the antigen-presenting cells of the spleen, and plans to test the method with other antigens besides ovalbumin. The researchers hope to obtain additional information and use it to achieve optimal conditions for the clinical application of EDIT technology.
Article A.Ukidve el al. Erythrocyte-driven immunization via biomimicry of their natural antigen-presenting function is published in the journal PNAS.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the Wyss Institute: Better vaccines are in our blood.