Table 4.
Classification of HSV-1-related vaccines.
Class | Name | Building Strategies | Result | Stage | Refs |
---|---|---|---|---|---|
Live attenuated vaccines | HSV-1 0NLS | Removal of codons 19 ~ 104 and 489 ~ 694 from the ICP0 gene, lack of the NLS region, and a portion of the C-terminal oligomerization domain of ICP0 | Protection against ocular HSV-1 attacks | Mouse model | [161] |
Elicits a strong B-lymphocyte response; maintains vision in the absence of HSV-1 glycoprotein M or thymidine kinase recognition | Mouse model | [162] | |||
HSV-l 0RlNG | Removal of codons 19 ~ 162 of the ICP0 gene removes several cysteine residues required for ICP0 E3 ligase activity | Significant short-term efficacy in ocular HSV-1 infection, but poor long-term prophylaxis | Mouse model | [163] | |
RVx-201 | HSV-2 0ΔNLS Mutation | Fatal HSV-2 genital excitation is extremely protective against HSV-2 reactivation | Guinea pig model | https://rationalvaccines.com/ | |
R2 | Encodes a pUL37 periplasmic protein with a mutation in region 2 | Reduces the severity of acute and recurrent HSV-2 disease. Does not cause neurological complications and provides better prophylaxis |
Guinea pig model | [164] | |
HSV-1-GS6264 | Five missense mutations in the gene encoding UL37 | HSV cannot invade nerves and prevent HSV infection | Guinea pig model | [165,166] | |
VC2 | gK aa31-68 and UL20 aa4-22 deletions in recombinant VC2 | Protective effect of live attenuated HSV-1 VC2 vaccine against HSV-2 genital infection in a guinea pig model of genital herpes. | Guinea pig model | [167] | |
Protective immune responses can be generated at the site of attack to protect against HSV-1-induced ocular pathogenesis | Mouse model | [168] | |||
Subunit vaccine | gB1 vaccine | Delivery of HSV-1 glycoprotein B (gB1) using feline immunodeficiency virus (FIV) vector LAW34 | Cross-neutralizing antibodies and cell-mediated responses were elicited, protecting against HSV-1 infection in mice. | Mouse model | [169–172] |
gD-2 | HSV-2 glycoprotein D (gD2-AS04) and the adjuvants aluminium hydroxide and 3-o-deacylated monophosphoryl lipid a (MPL) | Effective in preventing HSV-1 genital disease and infection, but not effective in preventing HSV-2 disease or infection | Clinical Phase III | [173] | |
GEN-003 | gD2/ICP4 + matrix M2 adjuvant | Demonstrates good safety and efficacy in clinical trials and stimulates humoral and cellular immune responses | Clinical Phase III | [174] | |
Trivalent subunit vaccine | HSV-2 subunits containing (gC2, gD2 and gE2) + CpG | Neutralizing antibodies and significant CD4+ T-cell responses were produced in rhesus monkeys. Protection against vaginal infections was up to 95 percent in guinea pigs after vaccination. |
Rhesus monkey model; Guinea pig model; Clinical Phase I |
[175, 16] |
|
Nucleic acid vaccine | Polyvalent DNA vaccine SL-V20 |
IL-21 and MIP-1α |
Enhanced antiviral T-cell response; Significant increase in 15-day survival and a significant reduction in vaginal viral load. |
Mouse model; Clinical Phase I |
[176] |
mRNA vaccine BNT163 |
Encodes three HSV-2 glycoproteins | Prevention of HSV cell entry and transmission, as well as counteracting the immunosuppressive properties of HSV. | Clinical Phase I | http://www.biontech.de/ | |
Nucleotide-modified mRNA lipid nanoparticle vaccines | mRNA lipid nanoparticles expressing glycoproteins gC, gD, gE (mRNA-LNP) | Prevents HSV-1 and HSV-2 genital herpes; ability to prevent nHSV in offspring is similar to subunit vaccines; BioNTech to begin Phase I clinicals in 2022. |
Mouse model; Guinea pig model; Clinical Phase I |
[177, 178] |
|
Replication-deficient vaccine | gH-deficient vaccine | HSV-1 gH coding deletion (SC16∆gH) | Significant reduction in oedema and erythema; Clinical trials were inconclusive |
Guinea Pig Model; Clinical trials |
[179, 166] |
ΔgD-2 | gD2-deficient HSV | Activation of a long-lasting ADCC effect providing active and passive protection against HSV-1 and HSV-2 | Mouse Model; Preclinical |
[180, 181] |