Vaccine delivery systems and administration routes: Advanced biotechnological techniques to improve the immunization efficacy

Abstract

Since the first use of vaccine tell the last COVID-19 pandemic caused by spread of SARS-CoV-2 worldwide, the use of advanced biotechnological techniques has accelerated the development of different types and methods for immunization. The last pandemic showed that the nucleic acid-based vaccine, especially mRNA, has an advantage in terms of development time; however, it showed a very critical drawback namely, the higher costs when compared to other strategies, and its inability to protect against new variants. This showed the need of more improvement to reach a better delivery and efficacy. In this review we will describe different vaccine delivery systems including, the most used viral vector, and also variable strategies for delivering of nucleic acid-based vaccines especially lipid-based nanoparticles formulation, polymersomes, electroporation and also the new powerful tools for the delivery of mRNA, which is based on the use of cell-penetrating peptides (CPPs). Additionally, we will also discuss the main challenges associated with each system. Finlay, the efficacy and safety of the vaccines depends not only on the formulations and delivery systems, but also the dosage and route of administration are also important players, therefore we will see the different routes for the vaccine administration including traditionally routes (intramuscular, Transdermal, subcutaneous), oral inhalation or via nasal mucosa, and will describe the advantages and disadvantage of each administration route.

Keywords: Antigen presentation; Cell-penetrating peptides (CPPs); Lipid-based nanoparticles; Mucosal immunization; Nucleic acid-based vaccines; Parenteral immunization; Polymersomes; SARS-CoV-2; Vaccine; Vaccine delivery strategy.

Fig. 1

New generation strategies used for SARS-CoV-2 vaccine development. A, a schematic structure of the SARS-CoV-2 virion; B, replication-incompetent vector vaccines, the genes E1, E3 are deleted, the spike CoV-2 protein or only the RBD are cloned behind CMV promoter, the AdVX fiber could be from different Ad type (5,26or35); C, mRNA vaccines (BNT162b2 and mRNA-1273) with Lipid nanoparticle (LNP); D, DNA vaccines with electroporation and E, virus; like particles (VLPs) display the spike protein on the surface but without genome.

Fig. 2

Schematic diagram representing the shape and structure of polymersome. The polymersome can encapsulate viral carriers such as adeno-associated viruses and Lentivirus, and non-viral carriers such as DNA and RNA. The encapsulated vectors could be hydrophilic (inside the vesicle) or hydrophobic drugs (in the membrane).

Fig. 3

Combination of CPPs with LNP and Polyplex for mRNA delivery. A) Combinations of CPPs with lipid-based nanoparticles and; B) CPPs with poly(ethylene glycol) (PEG)-GALA, and polycation to build a complex for mRNA transfer .

Fig. 4

vaccines administration via Nasal route using ChAdV, Adenoviral vector passe into the epithelial tissues by microfold cells (M cells) or passively through epithelial cell junctions or internalized by B cells or dendritic cells (DCs). B cells convert themselves to IgA plasma cells that produce IgA antibodies for neutralizing the pathogens at the mucosal surfaces (mucosal response) and conducted to the protection of upper and lower respiratory tracts Dendritic cells (DCs) with antigen migrate to mucosal-associated lymphoid tissues (MALTs) and present the antigen via major histocompatibility complex (MHC) class I and class II molecules to naïve CTL and naïve Th cells. The activation pathway produces cytotoxic T lymphocytes (CTL) and the Th1 cells and Th2 cells from naïve Th cells. Th1 cells activated macrophages to kill intracellular pathogens and stimulate NK cells (cellular response). The Th2 cells activated B cells to transform to IgG plasma cell that secret antibodies for neutralization of extracellular pathogens (humoral response) , .