Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cells & Viruses
2.2. Guinea Pig Inoculation, Clinical Assessment and Tissue Collection
2.3. Assessment Of HSV-2 Shedding in Vaginal Secretions
2.4. Explant Reactivation
2.5. Thymidine kinase (TK)-specific qPCR and LAT-specific RT-qPCR
2.6. Immunofluorescence (IF) and Fluorescent in Situ Hybridization (FISH)
2.7. Serum Immunoassays
2.8. Statistical Analysis
3. Results
3.1. Clinical Assessment in Guinea Pigs
3.2. Low Level Transient Viral Replication Occurred after Vaginal Inoculation with RVx202 but Not with RVx201 or with Intradermal Inoculation
3.3. Neither Vaccine Candidate Established Latency or Detectable Replicating Virus in Lumbosacral Dorsal Root Ganglia
3.4. Vaccine Candidates Induce Serum Antibody Response Following Intradermal Inoculation
4. Discussion
Vaccine Type | Agency | Antigen | Trial Phases Completed | Efficacy of HSV-2 Infection Prevention or Disease Amelioration |
---|---|---|---|---|
Subunit (monovalent) | GlaxoSmithKline | gD2 | 1–3 [53,54,55,56,57,58,59,60,61] | Infection: Not effective at preventing HSV-2 mediated infection/disease. Mild efficacy at preventing HSV-1 mediated infection/disease but not in men or HSV-1+ women [62,63,64]. |
Subunit (bivalent) | Genocea Biosciences | gD2, ICP4 [65] | 1–2 [66,67,68,69,70,71] | Disease: Transient six-month reduction in viral shedding. Reduced recurrence rates and duration in 20% up to 12 months [72]. |
Immune Design | gD2, UL19, UL25 [73] | 1–2 (active) [74] | Active study | |
Chiron (Novartis) | gD2, gB2 | 1–2 | Infection: 9% reduction over 18 months (Transient 50% reduction during first 5 months vs. placebo) Disease: Frequency of recurrence not reduced [75,76]. | |
Subunit (polyvalent) | Agenus | 22 HSV-2 Proteins [77] | 1–2 [78,79] | CD4+ and CD8+ T cell responses detected [80]. Phase 2 results not published. |
DNA (plasmid) | PowderMed (Pfizer) | ICP0, ICP4, ICP22, ICP27 | 1 [81,82] | Not published |
Vical | gD2, Tegument [83,84] | 1–2 [85,86] | Not published | |
Admedus | gD2 [87] | 1–2 | Disease: Reduced viral shedding ≈50% after booster compared to placebo [51,52]. | |
Replication deficient virus | Sanofi Pasteur | HSV-2 [88] | 1 2 (active) [74,89,90] | Active study. Shown to be immunogenic in HSV-1/HSV-2 seronegative participants [91] |
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Institutional Animal Care and Use Committee Statement
References
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Joyce, J.D.; Patel, A.K.; Murphy, B.; Carr, D.J.J.; Gershburg, E.; Bertke, A.S. Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs. Vaccines 2021, 9, 258. https://doi.org/10.3390/vaccines9030258
Joyce JD, Patel AK, Murphy B, Carr DJJ, Gershburg E, Bertke AS. Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs. Vaccines. 2021; 9(3):258. https://doi.org/10.3390/vaccines9030258
Chicago/Turabian StyleJoyce, Jonathan D., Anant K. Patel, Brandie Murphy, Daniel J.J. Carr, Edward Gershburg, and Andrea S. Bertke. 2021. "Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs" Vaccines 9, no. 3: 258. https://doi.org/10.3390/vaccines9030258