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. 2024 Nov 7;15(1):2425744. doi: 10.1080/21505594.2024.2425744

Table 4.

Classification of HSV-1-related vaccines.

Class Name Building Strategies Result Stage Refs
Live attenuated vaccines HSV-1 0ΔNLS 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 0ΔRlNG 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
  1. pGX27 with tpa, Flt3L, HSV-2 gB, and UL39;

  2. pGX27 with gD2, ICP0, and ICP4;

  3. pGX27 with IL-12,


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]