An Insight into Current Treatment Strategies, Their Limitations, and Ongoing Developments in Vaccine Technologies against Herpes Simplex Infections
Abstract
:1. Introduction
2. Herpes Simplex Virus (HSV): An Overview
2.1. Potential Targets for HSV Prevention
2.2. Interplay of HSV and Immune System
3. Therapeutic Strategies Available for Herpes Infections
3.1. Synthetic Therapeutics
3.2. Plant-Based Therapeutics
3.2.1. Plant Extracts
3.2.2. Phytocompounds
3.2.3. Essential Oils
3.3. Algae-Based Therapeutics
3.4. Fungi-Based Therapeutics
3.5. Nanotechnology-Based Therapeutics
3.6. Clinical Trial Evidence
4. Limitations of the Current Treatments and Challenges for Vaccine Development
4.1. Limitations of Current Treatments
4.2. Various Approaches Investigated for Meeting out the Limitations and Challenges
5. Preventive Methods for HSV through Vaccines
5.1. Inactivated Killed HSV Vaccines
5.2. Live-Attenuated Vaccines
5.3. Replication-Defective Virus Vaccines
5.4. Subunit HSV Vaccines
5.5. Nucleic Acid Vaccines
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Mechanism of Action | Potential Target | Drugs | References |
---|---|---|---|
Suppresses herpes virus genome replication at the protein level | DNA polymerase | 4-hydroxy-quinoline-3-carboxamide molecule and 8-hydroxyquinoline. | [52,53] |
Blocks attachments and invasion by targeting viral proteins | Glycoproteins | PRO 2000, polymethylene hydroquinone sulfonate, and cellulose sulphate | [55,56] |
Inhibits HSV DNA replication | Helicase primase complex | 2-amino-thiazole and thiazolylsulfonamide | [57] |
Ribonucleotide reductase inhibitors | Ribonucleotide reductase | Peptidomimetic inhibitors | [58,59] |
Inhibits polyamine biosynthetic pathway to block replication of HSV | Polyamine pathway | SAMDC inhibitors | [63,64] |
CDK-2 inhibitors | CDK-2 | Roscovitine | [65,66] |
Blocks attachment and penetration | Entry receptors (HVEM, glycosaminoglycans) | Anti-HVEM antibodies | [54] |
TLR inhibitors | TLR | G-ODN, CpG oligonucleotide | [67] |
Sr. No. | Type of Vaccine | Candidate Name | Modification in Vaccine | Host | Phase | Results | Origin | Refs. |
---|---|---|---|---|---|---|---|---|
1 | Inactivated vaccine | HSV-2 dl5-29 | deletions of UL5 and UL29 | mice and guinea pigs | Pre-clinical | enhance immune responses, protection against reactivates HSV infection | Harvard Medical School, Boston | [234] |
2 | Inactivated vaccine | SC16ΔgH | deletion of HSV-1 gH deletion | mice | Clinical | has no impact on viral shedding and inability to demonstrate immunity against reactivated genital herpes infections | Boston, Massachusetts | [16] |
3 | Replication-Defective Viral Vaccines | CJ2-gD2 | Dominant negative HSV-2 with CJ2-gD2 | guinea pigs | Pre-Clinical | provide protection against primary infection and reactivates HSV-2 genital infections | - | [235] |
4 | Replication-Defective Viral Vaccines | HSV-1 vhs-/ICP8- | deletions of vhs in an ICP8 | mice | Pre-Clinical | significantly enhances protective efficacy | - | [236] |
Δ41Δ29 | deletions in the gene for virion host shutoff (vhs) protein | BALB/c mice | Pre-Clinical | decreased the frequency of UV-B-induced recurrent viral shedding in mice with latent infection | Washington University School of Medicine | [237] | ||
5 | Replication-Defective Viral Vaccines | HSV529 | Deletion of UL5, UL29 in HSV-2 dl5-29 mice | mice and HSV-1 seropositive guinea pigs | immunogenicity reported | Sanofi Pasteur | [238] | |
HSV529 | - | human participants | Phase I | induced moderate CD4+ T-cell responses and neutralising antibodies in HSV-seronegative vaccine recipients | Sanofi Pasteur | [232,233] | ||
6 | Live-attenuated vaccine | HSV-2 ΔgD2 | Deletion of gD-2 | C57BL/6 or BALB/c mice | Pre-clinical | protection by non-neutralising Fc-mediated humoral responses | Albert Einstein College of Medicine | [222] |
C57BL/6 mice | Pre-clinical | infected mice were protected by gD-2 | Albert Einstein College of Medicine | [223] | ||||
7 | Live-attenuated vaccine | AD472 | Deletion of γ134.5 gene, UL55-56, UL43.5 and the US10-12 region | guinea pigs | Pre-clinical | reduce lesion development and infection severity in guinea pigs | Albert Einstein College of Medicine | [224] |
8 | Live-attenuated vaccine | NE-HSV-2 | Antigens such as gB2 and gD2 were used to make nanoemulsion | C57BL/6 mice | Pre-Clinical | reduction of reactivated lesions and viral shedding by more than 50% | BlueWillow Biologics | [239] |
9 | Live-attenuated vaccine | R2 | Mutated pUL37 gene in the R2 region | guinea pigs | Pre-Clinical | reduction of reactivated virus shedding | Thyreos LLC | [225,240] |
10 | Live-attenuated vaccine | HSV-1 VC2 | Mutations in glycoprotein K (gK) and UL20 | rhesus macaques | Pre-Clinical | induction of immune response | Louisiana State University | [241] |
- | guinea pigs | Pre-Clinical | diminishes HSV-2 replication | Louisiana State University | [242] | |||
Mutations in glycoprotein K (gK) and UL20 | mice | Pre-Clinical | protect mice against lethal intravaginal infection | Louisiana State University | [243] | |||
11 | Live-attenuated vaccine | HSV-2 0ΔNLS | Deletion of ICP0− | mice | Phase II | represent avirulence and immunogenicity | Southern Illinois University | [244] |
Pre-Clinical | protected against lethal challenge with wild-type HSV-2 | Southern Illinois University | [245] | |||||
12 | Subunit Vaccine | gD2 subunit vaccine | gD2 adjuvant with AS04 | HSV-1– and HSV-2–seronegative women | Phase 3 | efficacy against HSV-1 and HSV-1 genital disease was 58% and 35% respectively | GlaxoSmithKline | [246] |
girls aged 10–17 years | Phase 3 | vaccine was tolerated and immunogenic | GlaxoSmithKline | [247] | ||||
13 | Subunit Vaccine | HerpV | 32 synthetic 35mer HSV-2 peptides complexed with Hsc70 protein + QS21 (saponin adjuvant) | HLA-A2 transgenic mice | Pre-clinical | immunogenic, CD4(+) and CD8(+) T cell activators | Agenus | [248] |
HerpV+ QS-21 | human participant | Phase II (DC) | significant CD4+ T and CD8(+) T cell response | Agenus | [249] | |||
14 | Subunit Vaccine | HSV-2 trivalent vaccine | Combination of glycoproteins C, D, and E (gC2, gD2, gE2) | guinea pig | Pre-clinical | trivalent protein vaccine provides protection to prevent herpes infection | University of Pennsylvania | [250,251,252] |
rhesus macaques and guinea pig | Pre-clinical | viral shedding was reduced | University of Pennsylvania | [253] | ||||
guinea pigs | Pre-clinical | immune evasion domains on HSV-2 glycoproteins | University of Pennsylvania | [254] | ||||
15 | Subunit Vaccine | HSV1 gB lentiviral vector | HSV-1 glycoprotein B (gB1) with feline immunodeficiency virus (FIV) vector | C57BL/6 mice | Pre-Clinical | significant reduction in viral infectivity | University of Pisa, Italy | [255] |
16 | Subunit Vaccine | GEN-003 | gD2ΔTMR + M2 | seropositive participants | Completed Phase II (DC) | reduction in shedding and lesion rate was reported | University of Cincinnati, | [256] |
gD2 (truncated)+ICP4 fragment | healthy participants | Phase 2 | reduction in shedding rate and lesion rate | Genocea | [257,258] | |||
GEN-003/MM-2 | guinea pigs | Pre-clinical | elicits humoral immune responses, CD4+ and CD8+ T cells | Genocea | [259] | |||
17 | Subunit Vaccine | G103 | HSV-2 gD, deletions in UL19 and UL25 | Mice and guinea pigs | Pre-clinical | reductions of no. of lesions and lesion area | Immune Design | [226] |
18 | DNA Vaccines | COR-1 | gD2 ubiquitin tag with COR-1 DNA or placebo | HSV-2 seropositive subjects | Phase II | reduction in viral shedding | Admedus | [260] |
BALB/c mice | Pre-clinical | protects against lethal viral challenge and reduces ganglionic latency | University of Washington | [261] | ||||
19 | DNA Vaccines | pRSC-gD-IL-2123 | HSV-1 gD combined with IL-21 | mice | Pre-clinical | inhibition of HSK in HSV-1-infected mice | Southeast University, China | [262] |
20 | DNA Vaccines | Vaxfectin®-gD2/UL46/UL47 | HSV-2 glycoprotein D and UL46 and UL47 genes/Vaxfectin | mice | Pre-clinical | reduction of frequency of reactivated disease and viral shedding | Vical | [263,264] |
Vaxfectin-gD2 pDNA | pDNA + FL gD2 Vaxfectin | guinea pig | Pre-clinical | reduction in HSV-2 DNA copy number | University of Washington | [265] | ||
21 | DNA Vaccines | gB1s-NISV | NISV+HSV-1 gB+CpG | mice | Pre-Clinical | provides protection against a heterologous lethal vaginal challenge with HSV-2 | - | [266] |
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Sharma, D.; Sharma, S.; Akojwar, N.; Dondulkar, A.; Yenorkar, N.; Pandita, D.; Prasad, S.K.; Dhobi, M. An Insight into Current Treatment Strategies, Their Limitations, and Ongoing Developments in Vaccine Technologies against Herpes Simplex Infections. Vaccines 2023, 11, 206. https://doi.org/10.3390/vaccines11020206
Sharma D, Sharma S, Akojwar N, Dondulkar A, Yenorkar N, Pandita D, Prasad SK, Dhobi M. An Insight into Current Treatment Strategies, Their Limitations, and Ongoing Developments in Vaccine Technologies against Herpes Simplex Infections. Vaccines. 2023; 11(2):206. https://doi.org/10.3390/vaccines11020206
Chicago/Turabian StyleSharma, Divya, Supriya Sharma, Natasha Akojwar, Ayusha Dondulkar, Nikhil Yenorkar, Deepti Pandita, Satyendra K. Prasad, and Mahaveer Dhobi. 2023. "An Insight into Current Treatment Strategies, Their Limitations, and Ongoing Developments in Vaccine Technologies against Herpes Simplex Infections" Vaccines 11, no. 2: 206. https://doi.org/10.3390/vaccines11020206
APA StyleSharma, D., Sharma, S., Akojwar, N., Dondulkar, A., Yenorkar, N., Pandita, D., Prasad, S. K., & Dhobi, M. (2023). An Insight into Current Treatment Strategies, Their Limitations, and Ongoing Developments in Vaccine Technologies against Herpes Simplex Infections. Vaccines, 11(2), 206. https://doi.org/10.3390/vaccines11020206