Multifunctional Immunoadjuvants for Use in Minimalist Nucleic Acid Vaccines

Abstract

Subunit vaccines based on antigen-encoding nucleic acids have shown great promise for antigen-specific immunization against cancer and infectious diseases. Vaccines require immunostimulatory adjuvants to activate the innate immune system and trigger specific adaptive immune responses. However, the incorporation of immunoadjuvants into nonviral nucleic acid delivery systems often results in fairly complex structures that are difficult to mass-produce and characterize. In recent years, minimalist approaches have emerged to reduce the number of components used in vaccines. In these approaches, delivery materials, such as lipids and polymers, and/or pDNA/mRNA are designed to simultaneously possess several functionalities of immunostimulatory adjuvants. Such multifunctional immunoadjuvants encode antigens, encapsulate nucleic acids, and control their pharmacokinetic or cellular fate. Herein, we review a diverse class of multifunctional immunoadjuvants in nucleic acid subunit vaccines and provide a detailed description of their mechanisms of adjuvanticity and induction of specific immune responses.

Messenger RNA vaccines for cancer immunotherapy: progress promotes promise

“…Multifunctional innate immunoadjuvants have been co-delivered, including natural lipids, such as squalene, LPS, and saponin; synthetic lipids; polymers, including protamine, chitosan, and dextran sulfate; and synthetic polymers, such as polyethylenimine and poly-L-lysine (126). However, although co-delivery of certain non-lipidlike adjuvants with mRNA vaccines requires careful chemical packaging, preclinical studies with gardiquimod, a TLR7 agonist, in poly(lactic-co-glycolic acid) (PLGA)-core/shell RNA-nanoparticleinduced potent antitumor immune responses (127).…”

Black Phosphorus, an Emerging Versatile Nanoplatform for Cancer Immunotherapy

“…Generally, insufficient immunogenicity is a severe problem for vaccine application, leading to the failure of stimulating effective anticancer immune responses [ 136 ]. Therefore, immunostimulatory adjuvants are developed to both activate the innate immune responses and trigger tumor-specific immune responses [ 137 ]. Zhao and his colleagues reported the integration of bPEI-PEG coated BPNSs and CpG via electrostatic interaction [ 138 ].…”

PEGylation of mRNA by Hybridization of Complementary PEG-RNA Oligonucleotides Stabilizes mRNA without Using Cationic Materials

“…Cationic materials can also be designed to modulate the intracellular processes, for example, by facilitating endosomal escape [10] and preventing intracellular mRNA degradation [11]. Furthermore, pharmacological functionalities, such as adjuvanticity in vaccination, can be integrated to the cationic materials [12,13]. The complexation strategy exhibits potent outcomes in Pharmaceutics 2021, 13, 800 2 of 10 efficient mRNA delivery.…”

“…Furthermore, pharmacological functionalities, such as adjuvanticity in vaccination, can be integrated to the cationic materials [12,13]. The complexation strategy exhibits potent outcomes in Pharmaceutics 2021, 13, 800 2 of 10 efficient mRNA delivery. However, as cationic materials interact with anionic biomacromolecules, such as glycosaminoglycans on the cell surface [14], cationic carrier components frequently damage cells and tissues [15][16][17].…”