Delivery of mRNA Vaccine against SARS-CoV-2 Using a Polyglucin:Spermidine Conjugate

Abstract

One of the key stages in the development of mRNA vaccines is their delivery. Along with liposome, other materials are being developed for mRNA delivery that can ensure both the safety and effectiveness of the vaccine, and also facilitate its storage and transportation. In this study, we investigated the polyglucin:spermidine conjugate as a carrier of an mRNA-RBD vaccine encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. The conditions for the self-assembling of mRNA-PGS complexes were optimized, including the selection of the mRNA:PGS charge ratios. Using dynamic and electrophoretic light scattering it was shown that the most monodisperse suspension of nanoparticles was formed at the mRNA:PGS charge ratio equal to 1:5. The average hydrodynamic particles diameter was determined, and it was confirmed by electron microscopy. The evaluation of the zeta potential of the investigated complexes showed that the particles surface charge was close to the zero point. This may indicate that the positively charged PGS conjugate has completely packed the negatively charged mRNA molecules. It has been shown that the packaging of mRNA-RBD into the PGS envelope leads to increased production of specific antibodies with virus-neutralizing activity in immunized BALB/c mice. Our results showed that the proposed polycationic polyglucin:spermidine conjugate can be considered a promising and safe means to the delivery of mRNA vaccines, in particular mRNA vaccines against SARS-CoV-2.

Immunogenic Properties of the DNA Construct Encoding the Receptor-Binding Domain of the SARS-CoV-2 Spike Protein

“…Towards this end, the Fusogenix platform has been specifically designed, which represents a mixture of neutral lipids and small membrane proteins involved in membrane fusion. Although the toxicity of such liposomes appears to be significantly lower, they are still not devoid of certain important drawbacks both related to the liposomes themselves and the technically challenging transportation and storage of such vaccines which require cold chain maintenance [ 16 , 27 ].…”

“…The mixture was incubated for 2 more hours and the target product was purified from the unreacted components by gel-filtration in PBS-equilibrated G-25 Sefadex. To form the DNA–PGS complexes, DNA was mixed with PGS in a 1 : 10 mass ratio [ 15 , 16 ], and the product yield was assessed by the changes in the DNA electrophoretic mobility in 1% agarose gel.…”

“…A nucleotide sequence encoding the original leader sequence 176, a hybrid of the signal sequences of the two actively secreted proteins, namely, luciferase and fibroin, was attached to pVAX-RBD to ensure its efficient transport outside the cell. The polycationic polyglucine-spermidine conjugate (further referred to as PGS), which we previously used to develop the vaccines against HIV-1 [ 13 , 14 ] and Ebola virus [ 15 ], and the mRNA vaccine against SARS-CoV-2 [ 16 ], was used to package and deliver the DNA vaccine. Here, we report the results of the immunogenicity study of the PGS-enveloped pVAX-RBD plasmid as a potential DNA vaccine against SARS-CoV-2.…”

An Updated Review of SARS-CoV-2 Vaccines and the Importance of Effective Vaccination Programs in Pandemic Times

“…More research continues in the field of the delivery of mRNA vaccines, suggesting that, along with liposomes, other components could serve as coadjuvants. An example recently studied in mice is a conjugate of polyglucan and spermidine, with a positive charge, which aids in enveloping negatively charged mRNA [ 109 ].…”

Construction and Immunogenicity of Modified mRNA-Vaccine Variants Encoding Influenza Virus Antigens

“…Many studies [ 18 , 19 ] have demonstrated that mRNA-based vaccines are a promising platform with such useful features as flexibility, scalability, cheap production, and independence from the cold chain [ 15 ]. Due to the possibility of making a simple change to the target gene in an mRNA vaccine without modifying production technology, one can quickly respond to the emergence of new pandemic infectious agents, especially the influenza virus.…”