DNA Vaccines
Molecular adjuvants and immunogenicity of DNA vaccines in animals.
| Adjuvants | Antigens | Delivery | Host | Responses | |
| Costimulatory molecules | |||||
| CD80, CD86 | HIV-1 (Env, Gag, Pol) | DC, IM | Mouse Chimpanzee | +CMI | |
| CD40 LT | beta-gal | DC, SC | Mouse | +Ab, +CMI | |
| ICAM-1 | HIV-1 (Env) | DC, IM | Mouse | +CMI | |
| Cytokines | |||||
| IL-2, IFN-γ | HIV-1 (Env, Gag, Pol) | DC, IM | Mouse | +Ab, +CMI | |
| IL-6 | Influenza (HA) | DC, GG | Mouse | +Ab | |
| IL-2,12, IFN-γ | HBV | DC, IM | Mouse | +CMI | |
| TNF-α, IL-15 | HIV (Env, Gag, Pol) | DC, IM | Mouse | +CMI | |
| Toll like receptor adaptor/signaling molecules | |||||
| TRIF | Influenza (HA), tumor E7 | BC, IM/EP | Mouse | +CMI | |
| MyD88 | Influenza (HA), tumor E7 | BC, IM/EP | Mouse | +Ab | |
| FliC | Influenza A (Np) | DC, ID | Mouse | +Ab, +CMI | |
| IRF 1,3, 7 | Influenza virus (HA, Np) | DC/BC, IM | Mouse | +Ab, +CMI | |
| TBK-1 | P. f (SE36) | DC, IM | Mouse | +Ab, +CMI | |
| HMGB1 | HIV-1 (Gag, Env) | DC, IM/EP | Mouse | +Ab, +CMI | |
| DAI | Survivin | DC, ID | Mouse | +CMI | |
| chMDA5 | Influenza (HA) | DC, IM | Chicken | +Ab | |
| Ii | P. f (ME) | FC, IM | Mouse | +CMI | |
| Toxins/Viral proteins | |||||
| FrC | Sc-fv | FC, IM | Mouse | +Ab | |
| DTa | HIV (Gag) | BC, ID | Mouse | −CMI | |
| NSP4 | HCV NS3 | BC, ID | Mouse | +/−CMI | |
| VSVG | HIV (Gag) NS3 |
DC, ID BC, ID |
Mouse Mouse |
+CMI +/−CMI | |
| Heat shock proteins | |||||
| Calreticulin | mucin 1 HPV-16 E7 |
DC FC, GG |
Mouse Mouse |
+CMI +CMI | |
| HSP70 | HIV (Gag) | BC, ID | Mouse | +CMI | |
| Complement inhibitor | |||||
| IMX313 | HIV (Tat) | FC, ID | Mouse | +Ab, +CMI | |
| Cytolytic protein | |||||
| PRF | HIV (Gag) HCV (NS3) HCV (NS345B) |
BC, ID BC, ID BC, ID |
Mouse Mouse, Pig Mouse |
+CMI +CMI +CMI | |
Adjuvants: LT: ligand/trimer, IL: Interleukin, TNF: Tumor necrosis factor, TRIF: Toll-interleukin-1 receptor domain-containing adaptor-inducing beta interferon, MyD88: myeloid differentiation primary response, FliC: phase-1 flagellin, IRF: Interferon regulatory factor, TBK-1: TANK-binding kinase 1, HMGB1: High-mobility group box 1 protein, DAI: DNA-dependent activator of interferon (IFN) regulatory factors, chMDA5: melanoma differentiation-associated gene 5 product, FrC: Fragment C of tetanus toxin, DTa: Diphtheria toxin subunit A, NSP4: Nonstructural protein 4, li: MHC class II invariant chain, HSP: Heat shock protein, VSVG: Vesicular stomatitis virus, PRF: Perforin; Antigens: HIV: Human immunodeficiency virus, Env: Envelope, GAG: Group antigens, Pol: Reverse transcriptase, beta-gal: beta galactosidase, FMDV: Foot and Mouth Disease Virus, VP1: Virus protein 1, HBV: Hepatitis B virus, HA: Haemagglutinin, Sc-fv: Single chain fragment variable, Np: Nucleoprotein, P.f: Plasmodium falciparum, SE36: serine repeat antigen 36, HCV: Hepatitis C virus, NS3: Nonstructural protein 3, ME: Multiepitope string fused to the native P. falciparum T9/96 strain,NS345B: Nonstructural proteins 3, 4, 5B; Delivery: DC: Different constructs, BC: Bicistronic construct, FC: Fusion protein/single construct, IM: Intra muscular, SC: Subcutaneous, GG: Gene gun, EP: Electroporation, ID: Intradermal; Responses: +: Increase, −: Decrease, +/−: No significant change, CMI: T cell responses, Ab: Humoral responses;
Molecular adjuvants tested with DNA vaccines in humans.
| Adjuvants | Antigens | Delivery | Responses | Trial Phase | |
| IL-12, IL-15 | HIV-1 (Gag) | DC, IM | +/−Ab, +/−CMI | I | |
| GM-CSF, IL-2 | Her2 | RP, IM | +Ab, +CMI | I | |
| GM-CSF | CEA | RP, ID | +Ab, +CMI | I | |
| IL-2/Ig | HIV-1 Gag/Pol/Nef/Env | BC, IM | +Ab, +CMI | I | |
| IL-12 | HIV (MAG-Gag, Pol, Env, Nef, Tat, Vif) | DC, IM/EP | −Ab, +CMI | I | |
| IL-12 | HIV-1 (Env, Gag, Pol) | DC, IM/EP | +CMI | I | |
| GM-CSF | PAP | RPID | −Ab, +CMI | I/IIa | |
| HSP70 | HPV16 (E7) | FC, IM | −Ab, +/−CMI | I | |
| TNF-α, IL-15 | HIV (Env, Gag, Pol) | DC, IM | Mouse | +CMI | |
| Toll like receptor adaptor/signaling molecules | |||||
| TRIF | Influenza (HA), tumor E7 | BC, IM/EP | Mouse | +CMI | |
| MyD88 | Influenza (HA), tumor E7 | BC, IM/EP | Mouse | +Ab | |
| FliC | Influenza A (Np) | DC, ID | Mouse | +Ab, +CMI | |
| IRF 1,3, 7 | Influenza virus (HA, Np) | DC/BC, IM | Mouse | +Ab, +CMI | |
| TBK-1 | P. f (SE36) | DC, IM | Mouse | +Ab, +CMI | |
| HMGB1 | HIV-1 (Gag, Env) | DC, IM/EP | Mouse | +Ab, +CMI | |
| DAI | Survivin | DC, ID | Mouse | +CMI | |
| chMDA5 | Influenza (HA) | DC, IM | Chicken | +Ab | |
| Ii | P. f (ME) | FC, IM | Mouse | +CMI | |
| Toxins/Viral proteins | |||||
| FrC | Sc-fv | FC, IM | Mouse | +Ab | |
| DTa | HIV (Gag) | BC, ID | Mouse | −CMI | |
| NSP4 | HCV NS3 | BC, ID | Mouse | +/−CMI | |
| VSVG | HIV (Gag) NS3 |
DC, ID BC, ID |
Mouse Mouse |
+CMI +/−CMI | |
| Heat shock proteins | |||||
| Calreticulin | mucin 1 HPV-16 E7 |
DC FC, GG |
Mouse Mouse |
+CMI +CMI | |
| HSP70 | HIV (Gag) | BC, ID | Mouse | +CMI | |
| Complement inhibitor | |||||
| IMX313 | HIV (Tat) | FC, ID | Mouse | +Ab, +CMI | |
| Cytolytic protein | |||||
| PRF | HIV (Gag) HCV (NS3) HCV (NS345B) |
BC, ID BC, ID BC, ID |
Mouse Mouse, Pig Mouse |
+CMI +CMI +CMI | |