Advances in the polymeric delivery of nucleic acid vaccines

Abstract

Nucleic acid vaccines, especially messenger RNA (mRNA) vaccines, display unique benefits in the current COVID-19 pandemic. The application of polymeric materials as delivery carriers has greatly promoted nucleic acid vaccine as a promising prophylactic and therapeutic strategy. The inherent properties of polymeric materials render nucleic acid vaccines with excellent in vivo stability, enhanced biosafety, specific cellular uptake, endolysosomal escape, and promoted antigen expression. Although polymeric delivery of nucleic acid vaccines has progressed significantly in the past decades, clinical translation of polymer-gene vaccine systems still faces insurmountable challenges. This review summarizes the diverse polymers and their characterizations and representative formulations for nucleic acid vaccine delivery. We also discussed existing problems, coping strategies, and prospect relevant to applications of nucleic acid vaccines and polymeric carriers. This review highlights the rational design and development of polymeric vaccine delivery systems towards meeting the goals of defending serious or emerging diseases.

Keywords: cellular immunity; gene delivery; humoral immunity; nucleic acid vaccine; polymer.

Figure 1

Representative polymeric formulations used for vaccine delivery including polyplex, micelle, lipopolyplex, polymer engineered inorganic nanoparticles (NPs), hydrogel, and microneedle.

Figure 2

A. Chemical structure of chitin. B. Chemical structure of chitosan.

Figure 3

A. Chemical structure of linear PLL. B. Chemical structure of branched PLL.

Figure 4

A. Chemical structure of linear PEI. B. Chemical structure of branched PEI.

Figure 5

A. Chemical structure of PBAE. B. Chemical structure of PLGA.

Figure 6

A. Chemical structure of PAMAM. B. Chemical structure of pABOL.

Figure 7

Schematic illustrations of the concept of multifunctional core-shell polymeric NPs: transdermal DNA delivery, tracking of Langerhans cell migration, a pH-mediated DNA release mechanism, and gene expression in LNs. Adapted with permission from , copyright 2010 Elsevier.

Figure 8

A. GO and low molecular weight PEI (LPEI) are fabricated to form the injectable hydrogel (GLP-RO Gel) to encapsulate mRNA and R848. B. Illustration of the treatment intervals. C. Growth curves, D. gross images, and E. weight of tumors. F. H&E images of tumor tissues. G. Flow cytometry analysis of T cells in splenocytes. H. ELISA analysis of TNF-α and I. OVA-specific IgG in serum. Adapted with permission from , copyright 2021 American Chemical Society.

Figure 9

Representative microneedles including coated, dissolvable/degradable, and smart microneedles.

Figure 10

A. Deoxycholic acid conjugated LPEI (DA-LPEI) was applied to encapsulate R848 and S- or N-protein encoding DNA vaccines (DLP-RS or RN). B. The backing layer of microneedles can be separated from the skin and leave the microneedles in the skin by controlling temperature. C. Physiological mechanism of separable microneedle patch mediated antiviral immunity. Adapted with permission from , copyright 2021 American Chemical Society.

Figure 11

Summary of strategies for enhancing the efficacy of nucleic acid vaccines.

Figure 12

Different immunization routes (i.e. intradermal vaccination, subcutaneous vaccination, intramuscular vaccination, intravenous injection, mucosal administration, and intranodal injection) and APC (in the middle) uptake.