Cationic Polymers for the Delivery of the Ebola DNA Vaccine Encoding Artificial T-Cell Immunogen

Abstract

Background: According to current data, an effective Ebola virus vaccine should induce both humoral and T-cell immunity. In this work, we focused our efforts on methods for delivering artificial T-cell immunogen in the form of a DNA vaccine, using generation 4 polyamidoamine dendrimers (PAMAM G4) and a polyglucin:spermidine conjugate (PG). Methods: Optimal conditions were selected for obtaining complexes of previously developed DNA vaccines with cationic polymers. The sizes, mobility and surface charge of the complexes with PG and PAMAM 4G have been determined. The immunogenicity of the obtained vaccine constructs was investigated in BALB/c mice. Results: It was shown that packaging of DNA vaccine constructs both in the PG envelope and the PAMAM 4G envelope results in an increase in their immunogenicity as compared with the group of mice immunized with the of vector plasmid pcDNA3.1 (a negative control). The highest T-cell responses were shown in mice immunized with complexes of DNA vaccines with PG and these responses significantly exceeded those in the groups of animals immunized with both the combination of naked DNAs and the combination DNAs coated with PAMAM 4G. In the group of animals immunized with complexes of the DNA vaccines with PAMAM 4G, no statistical differences were found in the ability to induce T-cell responses, as compared with the group of mice immunized with the combination of naked DNAs. Conclusions: The PG conjugate can be considered as a promising and safe means to deliver DNA-based vaccines. The use of PAMAM requires further optimization.

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

“…To package mRNA, a polycationic polymer polyglucin:spermidine conjugate (PGS) was used. The choice of PGS was due to the fact that we had previously successfully tested it for the delivery of DNA vaccines [21][22][23]39]. PGS was included in the candidate HIV-1 vaccine CombiHIVvac, which passed the first phase of clinical trials [40,41] which demonstrated the safety of the vaccine.…”

“…Synthesis of polysaccharide conjugate was performed as described earlier in [21][22][23]. Briefly, polyglucin (dextran 40,000) was incubated with sodium periodate (40 molecules of sodium periodate per 1 molecule of dextran) for one hour and desalted by gel filtration on Sephadex G-25 in 50 mM carbonate buffer (pH 8.6).…”

Adaptive Immune Response to Vaccinia Virus LIVP Infection of BALB/c Mice and Protection against Lethal Reinfection with Cowpox Virus

“…ICS was performed according to a standard protocol as previously described [ 24 ]. Briefly, splenocytes isolated from mice 2 × 10 6 cells/well were plated in 24-well plates and stimulated with mix of VACV-specific peptides (SPYAAGYDL, SPGAAGYDL, VGPSNSPTF, KYGRLFNEI, GFIRSLQTI, and KYMWCYSQV) or with PMA (phorbol myristate acetate, 30 ng/mL) and ionomycin (1 µg/mL).…”

Developments in Treatment Methodologies Using Dendrimers for Infectious Diseases

“…The dendrimers delivered artificial polyepitope T-cell immunogens in the form of a DNA. Due to relatively low immunogenicity, this approach needs more research [ 63 ].…”