Advances in saRNA Vaccine Research against Emerging/Re-Emerging Viruses
Abstract
:1. Introduction
2. Structural Characterization of saRNAs
3. Design Strategies for saRNAs
4. Administration Routes and Delivery Systems for saRNAs
5. saRNA Vaccines against Emerging/Re-Emerging Viruses
5.1. SARS-CoV-2
5.2. HIV-1
5.3. Influenza Viruses
5.4. Other Viruses
6. Challenges and Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Delivery Approaches | Features | Advantages | Disadvantages | Examples of References | |
---|---|---|---|---|---|
Naked | Formulated in buffer; direct injection | Simple; low cost | RNA susceptible to degradation by RNase | [57,58,59] | |
Gene gun or electroporation | Physical techniques; device-mediated | Safe; simple | Harmful to cells; low efficiency | [2,17] | |
Viral delivery | Viral replicon particles (VRPs) | Single-cycle infectious particles | High cost; anti-vector neutralizing immunity | [53,54] | |
Nonviral delivery | Liposomes | Lipid mixtures composed of DOPE and a cationic lipid (DOTAP or DDA) | Low toxicity and biocompatibility | Low encapsulation capacity | [60] |
Polymer polyethylenimine (PEI) | Cationic polymers being used to formulate nanoparticles | Low cost, high transfection efficiency, and high escape efficiency from intracellular bodies | High cation density can result in severe toxicity | [5,61] | |
LNP | Composed of a complex amino lipid (either ionizable or non-ionizable), a phospholipid, cholesterol, a poly (ethylene glycol)-lipid conjugate, and the RNA | Protects RNA against degradation; assists in endocytosis and endosomal escape; markedly enhances the potency of the saRNA | High cost; repeated application can induce an immune response against polyethylene glycol; difficult to be stored in large quantities and for long periods of time; ionizable amino lipids have certain toxicity | [3,14,34,61,62] | |
CNE | A mixture of an aqueous phase containing buffer and Tween 80 with an oil phase containing Span 85, DOTAP, and squalene | Effective; well tolerated for saRNA; enhances RNA delivery, and thereby substantially increases the potency of the vaccine; the duration and magnitude of immunogen expression are similar to the LNP delivery system | Limited to saRNA use | [6,51,63,64,65] | |
Cationic polymer “pABOL” | Bioreducible, linear, cationic polymer; higher transfection efficiency and lower cytotoxicity compared to commercially available PEI | Less cytotoxic at higher molecular weights; enhances the expression level of immunogen and the cellular uptake; can be synthesized on a large scale and produced easily | Not described | [33] | |
Neutral lipopolyplexes (LPPs) | Ternary complexes composed of a cationic polymer and mannosylated liposomes | Stable in vitro and can delivery RNAs to DCs; protects RNAs from degradation | Not described | [35] | |
NLC | Composed of a hybrid liquid squalene and solid glyceryl trimyristate (Dynasan 114) core | Highly stable; can be manufactured and stored separately from RNAs; sufficient RNA-loading capacity; specific physicochemical modifications can change the intensity of the immune responses | Not described | [10] | |
Modified dendrimer nanoparticle (MDNP) | Composed of ionizable dendrimer-based nanomaterial, a lipid-anchored PEG and the RNA | Stable; protects RNA payloads; free of infectious contaminants and virtually endotoxin-free; no systemic increase in inflammatory cytokine production | Not described | [64] |
Viruses | Immunogen | Replicon | Species | Delivery System | Administration Route |
---|---|---|---|---|---|
SARS-CoV-2 [62] | Spike protein | VEEV | Human | LNP | IM |
SARS-CoV-2 [79] | Spike protein | VEEV | Human | LNP | IM |
SARS-CoV-2 [80] | Spike protein | VEEV | Human | LNP | IM |
SARS-CoV-2 [81] | Spike protein | VEEV | Hamsters | LNP | IM |
SARS-CoV-2 [82] | RBD and NP | VEEV | Mice/hamsters | LNP | IM |
SARS-CoV-2 [9] | Spike protein | VEEV | Mice | LNP | IM |
SARS-CoV-2 [83] | Spike protein | VEEV | Mice | LNP | IM |
SARS-CoV-2 [84] | RBD and full-length spike protein | Unknown | Mice/rhesus macaques | LNP | IM |
SARS-CoV-2 [85] | Spike protein | VEEV | Mice/pigtail macaques | LIONs | IM |
SARS-CoV-2 [18] | Spike protein | Norovirus GI | Mice | LNP | Intranasal |
HIV-1 [86] | Env | VEEV | Mice | LNP | IM |
HIV-1 [60] | Gag/Pol mosaic | SFV | Mice | Polyplus Transfection | IM |
HIV-1 [63] | Env | VEE–SINV | Rhesus macaques | CNE | IM |
HIV-1 [61] | Native-like Env trimers | VEEV | Mice, guinea pigs, rabbits, macaques | PEI | IM |
HIV-1 [2] | Env | VEE–SINV | Mice | Electroporation (naked) | IM |
HIV-1 [6] | Env | VEE–SINV | Rabbits/rhesus macaques | CNE | IM |
HIV-1 [3] | Env | VEE–SINV | Mice | LNP | IM |
Influenza virus [5] | HA | Not described | Mice | PEI | IM |
Influenza virus [67] | HA | Alphavirus replicon | Mice | LNP | IM |
Influenza virus [69] | HA | VEE–SINV | Mice/ferrets | CNE | IM |
Influenza virus [64] | HA | VEEV | Mice | MDNP | IV |
Influenza virus [33] | HA | VEEV | Mice | pABOL | IM |
Influenza virus [34] | HA | Not described | Mice | MLNP | IM/IV |
Influenza virus [35] | HA | VEEV | Mice | LPP | IM |
Influenza virus [47] | HA | Trans-amplifying | Mice | Naked | ID |
Influenza virus [59] | NP | SFV | Mice | Naked | IM |
Influenza virus [13] | HA/NP | CSFV | Mice/rabbits | Chitosan NGA | IM |
Influenza virus [87] | M1/NP | VEE–SINV | Mice | LNP | IM |
Influenza virus [88] | NP | VEE–SINV | Mice | LNP | IM |
Influenza virus [15] | HA/NP | CSFV | Pigs | CPP PEI | IM |
Influenza virus [14] | NP | CSFV | Mice | Cationic lipid | IH |
Rabies virus [51] | Glycoprotein G | VEE–SINV | Rats | CNE | IM |
Rabies virus [32] | Glycoprotein G | VEE–SINV | Mice | Liposome, nanoparticle, CNE | IM |
Rabies virus [89] | Glycoprotein G | VEE–SINV | Rats | LNP/CNE | IM |
ZIKV [49] | prM-E | VEEV | Mice | Electroporation (naked) | ID, IV. |
ZIKV [10] | prM-E | VEEV | Mice | NLC | Intrasplenic |
ZIKV [50] | prM-E | VEEV | Mice | MDNP | IV |
RSV [6] | F glycoprotein | VEE–SINV | Mice | CNE | IM |
RSV [3] | F glycoprotein | VEE–SINV | Mice/Rats | LNP | IM |
RSV [58] | F glycoprotein | SFV | Mice | Naked | IM |
Ebola virus [64] | Glycoprotein | VEEV | Mice | MDNP | IV |
TBEV [16,17] | Capsid-null TBEV particles | TBEV | Mice | Gene gun | / |
VEEV [70] | Glycoprotein | VEEV | Mice | CNE | IM |
LIV [58] | prME | SFV | Mice | Naked | IM |
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Liu, Y.; Li, Y.; Hu, Q. Advances in saRNA Vaccine Research against Emerging/Re-Emerging Viruses. Vaccines 2023, 11, 1142. https://doi.org/10.3390/vaccines11071142
Liu Y, Li Y, Hu Q. Advances in saRNA Vaccine Research against Emerging/Re-Emerging Viruses. Vaccines. 2023; 11(7):1142. https://doi.org/10.3390/vaccines11071142
Chicago/Turabian StyleLiu, Yalan, Yuncheng Li, and Qinxue Hu. 2023. "Advances in saRNA Vaccine Research against Emerging/Re-Emerging Viruses" Vaccines 11, no. 7: 1142. https://doi.org/10.3390/vaccines11071142