Table 1.
Current herpes simplex vaccines under preclinical development.
| Type of Vaccine | Description | Adjuvant | Type of Study | Animal Model | Route of Challenge | Results | Year | Refs. |
|---|---|---|---|---|---|---|---|---|
| Vectored/DNA/RNA | Polyvalent HSV-2 glycoprotein DNA vaccine (gB2, gC2, gD2, gE2, gH2, gL2, and gI2) | DNA encoding IL-12 | P | Mouse (Balb/c) | Genital HSV-2 | DNA vaccines targeting optimal combinations of surface glycoproteins provide better protection than gD alone and similar survival benefits and disease symptom reductions compared with a potent live-attenuated HSV-2 0ΔNLS vaccine. However, mice vaccinated with HSV-2 0ΔNLS clear the virus much faster. | 2017 | [10] |
| Vectored/DNA/RNA | Nucleoside-modified mRNA encoding HSV-2 gC2, gD2, and gE2 | Lipid nanoparticle (LNP) | P | Mouse (Balb/c) and guinea pig (Hartley) | Genital HSV-2 | The trivalent mRNA vaccine outperformed trivalent subunit-based vaccines, reducing latent viral load, shedding infectious virus, and PCR positive vaginal swabs. | 2019 | [11] |
| Vectored/DNA/RNA | Modified vaccinia virus Ankara (MVA) expressing HSV-2 gD2 | NA | Vector Stability |
NA | NA | Serial passage of recombinant vaccinia vectors led to the loss of transgene expression | 2020 | [12] |
| Subunit | Asymptomatic CD8+ T cell peptide epitopes (UL44 aa400–408, UL9 aa196–204, and UL25 aa572–580) | CpG (Prime) followed by AAV8 vectored CXCL10 (Pull) | P | HLA transgenic rabbits | Ocular HSV-1 | Prime/pull was effective at drawing HSV-1-specific CD8+ T cells to the cornea and trigeminal ganglia, reducing disease. | 2018 | [13] |
| Subunit | Bivalent HSV-2 Subunit (gD2 and gB2) | Nanoemulsion adjuvant NE01 | P/T | Guinea pig (Hartley) | Genital HSV-2 | Intranasal (IN) vaccination significantly reduced acute and recurrent disease scores and latent viral load compared to a placebo. Therapeutically, IN vaccination reduced recurrent lesion sores, days with the disease, animals shedding virus, and virus-positive vaginal swabs. | 2019 | [14] |
| Subunit | Trivalent HSV-2 subunit vaccine (gC2, gD2, and gE2) | CpG (5′-TCCATGACGTTCCTGACGTT-3’)/Alum | P | Neonatal Mouse (C57BL/6) | Intranasal (HSV-1/HSV-2) | Maternal vaccination protected offspring against neonatal disseminated disease and mortality from HSV-1 and HSV-2. | 2020 | [15] |
| Live-Attenuated | Replication-Competent Controlled HSV-1 Vectors (HSV-GS3 and HSV-GS7) | NA | P | Mouse (Swiss Webster) | Rear Footpad HSV-1 | Inactivated HSV-1 vectors offered equivalent protection to inactivated vaccines. Activation of these controlled vaccines increased vaccine efficacy over inactivated vaccines. | 2018 | [16] |
| Live-Attenuated | Replication-defective HSV-2 dl5-29 (Lacking UL5 and UL29) | NA | P | Mouse (C57BL/6) and Neonatal Mouse (C57BL/6) | Adult Ocular (Corneal HSV-1 infection), Neonatal Mouse (Intranasal HSV-1 Infection) | Maternal vaccination led to the transfer of HSV-specific antibodies into neonatal circulation that protected against neonatal neurological disease and death. | 2019 | [17] |
| Live-Attenuated | HSV-1 0ΔNLS | NA | P | Mouse (C57BL/6) | Ocular HSV-1 | Sterile immunity to ocular HSV-1 challenge with reduced infection of the nervous system. Vaccination preserved cornea free of pathology and complete preservation of visual acuity. | 2019 | [18] |
| Live-Attenuated | The non-neuroinvasive VC2 HSV-1 vaccine (Deletion of gK aa31-68 and UL20 aa4-22) | NA | P | Guinea pig (Hartley) | Genital HSV-2 | The live-attenuated VC2 vaccine outperformed the gD2 subunit vaccine in the durability of vaccine-induced protection 6 months post-vaccination. | 2019 | [19] |
| Live-Attenuated | R2 non-neuroinvasive HSV-1 vaccine (HSV1-GS6264, 5 missense mutations in UL37) | NA | P | Guinea pig (Hartley) | Genital HSV-2 | The live-attenuated prophylactic HSV vaccine, R2, was effective in the guinea pig model of genital HSV-2, especially when administered by the ID route. | 2020 | [20] |
| Live-Attenuated | NA | P | Mouse (Balb/c) | Ocular HSV-1 | VC2 vaccination in mice produced superior protection and morbidity control compared to its parental strain HSV-1 (F). | 2020 | [21] |
Abbreviations: P—Prophylactic, T—Therapeutic.