Targeting of mRNA vaccines to antigen-presenting cells via central immunoreceptor
(2024) KEMR45 20241Department of Chemistry
- Abstract
- The success of mRNA vaccines against the SARS-CoV-2 virus during the pandemic highlighted the potential of the technology and opened the door for applications beyond vaccines. However, the low degree of immune response observed in some individuals necessitates continued improvement in the technology. One promising approach is to target the vaccine delivery to specific cells involved in the immune response. In this project, I aim to study if three bacterial proteins coated on the lipid nanoparticles of mRNA vaccines have the potential to improve the delivery, by targeting of an immune receptor Receptor D. If successful, this could create a versatile platform to potentiate mRNA delivery.
To study the potential of the platform, we stimulated... (More) - The success of mRNA vaccines against the SARS-CoV-2 virus during the pandemic highlighted the potential of the technology and opened the door for applications beyond vaccines. However, the low degree of immune response observed in some individuals necessitates continued improvement in the technology. One promising approach is to target the vaccine delivery to specific cells involved in the immune response. In this project, I aim to study if three bacterial proteins coated on the lipid nanoparticles of mRNA vaccines have the potential to improve the delivery, by targeting of an immune receptor Receptor D. If successful, this could create a versatile platform to potentiate mRNA delivery.
To study the potential of the platform, we stimulated a Receptor D-expressing reporter cell line with protein, protein-coated nanobeads, and protein-coated lipid nanoparticles carrying eGFP mRNA. Furthermore, we constructed peptide libraries covering each protein sequence and studied the binding affinities using biolayer interferometry to identify shorter binding sequences for refining the targeting strategy and replace full-length proteins. The results show that Protein E and, to a lesser degree, Protein L and Protein F can activate Receptor D when coated on a bead- or LNP surface, but not in solution. Importantly, coating the LNP surface with bacterial protein increased the expression of eGFP mRNA, indicating that the strategy has the potential to potentiate mRNA vaccine effects. While the results from the peptide screening using biolayer interferometry are inconclusive at the project endpoint, progress has been made toward identifying a shorter peptide for surface coating. (Less) - Popular Abstract
- With the deployment and apparent success of mRNA vaccines in the Covid-19 pandemic, researchers have continued working to improve the technology. mRNA vaccines consist of small hollow vesicles, only 50-200 nm in diameter, called lipid nanoparticles (LNPs), which contain and protect the mRNA. Upon injection, the mRNA is taken up by cells. The cells will then use their own machinery to translate the mRNA into multiple copies of the virus-associated protein, which the body can react to. While the mRNA vaccines work well for large parts of the population, some people do not gain sufficient protection. These can include the elderly or individuals with impaired immune systems, such as patients taking medicine after transplants or those with an... (More)
- With the deployment and apparent success of mRNA vaccines in the Covid-19 pandemic, researchers have continued working to improve the technology. mRNA vaccines consist of small hollow vesicles, only 50-200 nm in diameter, called lipid nanoparticles (LNPs), which contain and protect the mRNA. Upon injection, the mRNA is taken up by cells. The cells will then use their own machinery to translate the mRNA into multiple copies of the virus-associated protein, which the body can react to. While the mRNA vaccines work well for large parts of the population, some people do not gain sufficient protection. These can include the elderly or individuals with impaired immune systems, such as patients taking medicine after transplants or those with an immunodeficiency disorder. This project focused on creating a new platform to potentiate the mRNA vaccines by attaching bacterial proteins to the outside of the LNPs. The goal is to target the delivery to and activate specific immune cells that have a receptor called Receptor D. The three bacterial proteins have been indicated to have a binding affinity for Receptor D and these cells are important for the body to develop immunity. To test this theory, we used engineered cells possessing the receptor Receptor D and stimulated them with nanoparticles and LNPs coated in the proteins and loaded with mRNA. When the engineered cells become activated, they produce a colorful chemical that can be measured. If the cells are also able to translate the mRNA to protein, the protein will produce a fluorescent light. Our results showed a significant increase in cell activation using the protein-coated nanoparticles and LNPs compared to uncoated. We were also able to observe an increase in the number of protein copies produced by the cells from the mRNA, indicating that the platform has the potential to work. At the same time, we investigated if we could identify the specific part of the bacterial proteins that interacted with Receptor D, using an instrument that can detect interactions between the receptor and proteins. It is favorable to use smaller parts of proteins instead of whole ones since they are easier to work with, simplifying future production and improvements. However, at the project endpoint we were unsuccessful in identifying the specific parts. Future work would include further investigation into finding those parts of the bacterial proteins able to bind Receptor D and use them to activate the cells. If successful, the potentiated mRNA vaccines could be a platform to improve the efficacy of future vaccines. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9154835
- author
- Öhnström, Valdemar LU
- supervisor
- organization
- course
- KEMR45 20241
- year
- 2024
- type
- H2 - Master's Degree (Two Years)
- subject
- keywords
- Biochemistry, Immunology, mRNA vaccine
- language
- English
- id
- 9154835
- date added to LUP
- 2024-05-30 13:26:20
- date last changed
- 2024-05-30 13:26:20
@misc{9154835,
abstract = {{The success of mRNA vaccines against the SARS-CoV-2 virus during the pandemic highlighted the potential of the technology and opened the door for applications beyond vaccines. However, the low degree of immune response observed in some individuals necessitates continued improvement in the technology. One promising approach is to target the vaccine delivery to specific cells involved in the immune response. In this project, I aim to study if three bacterial proteins coated on the lipid nanoparticles of mRNA vaccines have the potential to improve the delivery, by targeting of an immune receptor Receptor D. If successful, this could create a versatile platform to potentiate mRNA delivery.
To study the potential of the platform, we stimulated a Receptor D-expressing reporter cell line with protein, protein-coated nanobeads, and protein-coated lipid nanoparticles carrying eGFP mRNA. Furthermore, we constructed peptide libraries covering each protein sequence and studied the binding affinities using biolayer interferometry to identify shorter binding sequences for refining the targeting strategy and replace full-length proteins. The results show that Protein E and, to a lesser degree, Protein L and Protein F can activate Receptor D when coated on a bead- or LNP surface, but not in solution. Importantly, coating the LNP surface with bacterial protein increased the expression of eGFP mRNA, indicating that the strategy has the potential to potentiate mRNA vaccine effects. While the results from the peptide screening using biolayer interferometry are inconclusive at the project endpoint, progress has been made toward identifying a shorter peptide for surface coating.}},
author = {{Öhnström, Valdemar}},
language = {{eng}},
note = {{Student Paper}},
title = {{Targeting of mRNA vaccines to antigen-presenting cells via central immunoreceptor}},
year = {{2024}},
}