Table 3.
Advanced strategies for mucosal vaccine delivery.
| Barrier | Type of vaccine | Carrier | Antigen/epitope | Disease | Ref./NCT |
|---|---|---|---|---|---|
| Oral mucosa | Subunit vaccine | Mucoadhesive wafers | HIV gp140 protein | HIV | 69 |
| Microneedle arrays | HBsAg | HBV | 132 | ||
| SIMPL tablet | OVA | / | 67 | ||
| / | Nanofibrous mucoadhesive films | / | / | 68 | |
| Gastrointestinal mucosa | Inactivated vaccine | Chitosan and alginate delivery carriers | HEV71 | Hand-foot-and-mouth disease | 133 |
| Attenuated vaccine | Albumin–chitosan matrix microsphere | Typhoid Vi® antigen | Typhoid | 134 | |
| Ad-vectored vaccine | Adenovirus type-4 | Hemagglutinin from H5N1 virus | Influenza | 72 | |
| Adenovirus type-5 | Hemagglutinin from H1N1 virus | Influenza | NCT02918006, Phase Ⅱ | ||
| Adenovirus type-5 | Spike protein | COVID-19 | NCT04845191, Phase I/Ⅱ | ||
| Adenovirus type-5 | Spike protein and nucleocapsid | COVID-19 | NCT04732468, Phase I | ||
| Chimpanzee Adenovirus | Hepatitis B virus | Hepatitis B | NCT04297917, Phase Ⅰ | ||
| Subunit vaccine | Pollen grains or ragweed pollen | OVA | / | 135,136 | |
| Flagellin and mannosamine coated poly (anhydride) NPs | OVA | / | 137 | ||
| Porous silica NPs | BSA | / | 138 | ||
| CPP-rich PEGylated NPs | Recombination urease subunit B (rUreB) | Helicobacter pylori infection | 77 | ||
| PMMMA-PLGA | Surface immunogenic protein (SIP) from group B Streptococcus (GBS) | Streptococcus agalactiae infection | 139 | ||
| DNA vaccine | Poly (lactide-co-glycolide) microparticle | A rotavirus VP6 DNA | Infant diarrhea | 140 | |
| Chitosan NPs | LTB (L)、STXB (S) and CTXB (C) | Diarrhea | 141 | ||
| PLGA NPs | Hepatitis B virus (HBV) HBsAg | Hepatitis B | 140,142 | ||
| Poly(d,l-lactide-co-glycolide) (PLG) microparticle | gp160 | HIV | 143 | ||
| Respiratory tract mucosa | Ad-vectored vaccine | Adenovirus vector | RBD domain of Spike protein | COVID-19 | NCT04679909, Phase I |
| Adenovirus vector | Spike protein | COVID-19 | NCT04751682, Phase I | ||
| Adenovirus vector | 85A antigen | Tuberculosis | NCT04121494, Phase I | ||
| Adenovirus vector | Spike protein | COVID-19 | NCT04552366, Phase I | ||
| Adenovirus vector | Spike protein | COVID-19 | NCT04816019, Phase Ⅰ | ||
| Adenovirus vector | Influenza Vietnam 1194 Hemagglutinin | H5N1 Influenza | NCT01443936, Phase Ⅰ | ||
| Adenovirus vector | Spike protein | COVID-19 | NCT05043259, Phase Ⅰ/Ⅱ | ||
| Recombinant virus | CaP nanoshell | Recombinant dengue virus | Dengue | 144 | |
| Subunit vaccine | Polysaccharidic lapidated NPs | OVA | / | 145 | |
| Bacterium-like particle | RSV fusion (F) protein | RSV | 146 | ||
| N-Trimethyl chitosan NPs | OVA | / | 147 | ||
| Poly (γ-glutamic acid) NPs | OVA | / | 148 | ||
| PCL-PEI and PCL-PEG polymeric hybrid micelle | Citra conic anhydride-modified OVA | / | 149 | ||
| Adeno-associated virus type 12 | Influenza A nucleoprotein | Influenza | 150 | ||
| Nanoemulsion | N-Acetyl-neuroaminyllactose-binding hemagglutinin protein | Helicobacter pylori infection | 151 | ||
| Porous maltodextrin-based lipid core NPs | Toxoplasma gondii antigens | Toxoplasma gondii infection | 152 | ||
| Nanogel | Clostridium botulinum type-A neurotoxin BoHc/A | BoNT | 153 | ||
| Hybrid NPs | BSA | / | 154 | ||
| Thermal-sensitive hydrogel | Shigella flexneri outer membrane vesicles (OMV), split H5N1 antigen | Influenza | 155,156 | ||
| DNA vaccine | Mannosylated protamine sulphate | Model DNA: anti-GRP DNA | / | 157 | |
| mRNA vaccine | PEG12KL4 | Luciferase mRNA | RSV infection | 97 | |
| Cationic cyclodextrin-polyethylenimine 2k conjugate (CP 2k) | gp120 | HIV | 99 | ||
| Hyperbranched poly (beta amino esters) (hPBAEs) | Luciferase | / | 102 | ||
| Vaginal mucosa | Inactivated vaccine | Polystyrene nanospheres | HIV-1 | HIV | 158 |
| Subunit vaccine | Calcium phosphate (CAP) NPs | HSV-2 protein | HSV | 159 | |
| Poly-acrylic acid (Carbopol) gel | HIV-1 CN54 gp140 | HIV | 160, 161, 162 | ||
| Hydroxyethylcellulose (HEC) gel | HIV-1 CN54 gp140 | HIV | 163 | ||
| Thermosensitive poloxamer | HIV-1 CN54 gp140 | HIV | 164,165 | ||
| Liposome-loaded HEC gelling rods | HIV-1 CN54 gp140 | HIV | 108,166 | ||
| Liposome-loaded microneedle array | HSV-2 gD | HSV | 29 | ||
| Ad-vectored vaccine | Ad | HIV-1 gp140CF | HIV | 167,168 | |
| rAd5 | HIV gag | HIV | 169 | ||
| Recombinant vaccine | Pseudovirion | Recombinant HPV-SIV gag | HPV | 170 | |
| Recombinant virus | HIV gp160 and gag192-208 | HIV | 35 | ||
| Recombinant virus | HIV gag p24 | HIV | 171 | ||
| VLP vaccine | Virus-like NPs | HIV-1 gag | HIV | 172 | |
| Virus-like NPs | HIV-1 gag p55 | HIV | 173 |
Ad, adenovirus; ALG, alginate; CMC, carboxymethylcellulose; COPD, chronic obstructive pulmonary disease; ETEC, Escherichia coli; ETSD, enhanced T-cell stimulation domain; LAIVs, live attenuated influenza vaccines; MVA, modified vaccinia ankara; PMMMA-PLGA, Poly[(methyl methacrylate)-co-(methyl acrylate)-co-(methacrylic acid)]-poly(d,l-lactide-co-glycolide); rPA, recombinant protein; RSV, respiratory syncytial virus; UTI, urinary tract infection.