A novel nonlive, adjuvanted herpes zoster subunit vaccine: a report on the emerging clinical data and safety profile

Brosio, Federica; Masetti, Giulia; Matteo, Giulio; Stefanati, Armando; Gabutti, Giovanni

doi:10.2147/idr.s148303

Cited by 11 publications

(6 citation statements)

References 59 publications

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“…The characterization of T cell responses during natural human infections with VZV, HIV, and influenza virus has defined critical epitopes on target antigens and advanced the development of subunit vaccines (28)(29)(30). In this study, we comprehensively explored T cell responses to gB in healthy EBV carriers with and without viral reactivation and in patients with NPC using an overlapping peptide library covering the entire gB sequence.…”

Section: Discussionmentioning

confidence: 99%

T Cell Epitope Screening of Epstein-Barr Virus Fusion Protein gB

Chen

Zhang

et al. 2021

J Virol

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Glycoprotein B (gB) is an essential fusion protein for the Epstein-Barr virus (EBV) infection of both B cells and epithelial cells and is thus a promising target antigen for a prophylactic vaccine to prevent or reduce EBV-associated disease. T cell responses play key roles in the control of persistent EBV infection and in the efficacy of a vaccine. However, to date, T cell responses to gB have been characterized for only a limited number of human leukocyte antigen (HLA) alleles. Here, we screened gB T cell epitopes in 23 healthy EBV carriers and ten patients with nasopharyngeal cancer (NPC) using a peptide library spanning the entire gB sequence. We identified twelve novel epitopes in the context of seven new HLA restrictions that are common in Asian populations. Two epitopes, gB214-223 and gB840-849, restricted by HLA-B*58:01 and B*38:02, respectively, elicited specific CD8+ T cell responses to inhibit EBV-driven B cell transformation. Interestingly, gB-specific CD8+ T cells were more frequent in healthy viral carriers with EBV reactivation than in those without EBV reactivation, indicating that EBV reactivation in vivo stimulates both humoral (VCA-gp125-IgA) and cellular responses to gB. We further found that most gB epitopes are conserved among different EBV strains. Our study broadens the diversity and HLA restrictions of gB epitopes and suggests that gB is a common target of T cell responses in healthy viral carriers with EBV reactivation. In particular, the precisely mapped and conserved gB epitopes provide valuable information for prophylactic vaccine development. Importance T cells are crucial for the control of persistent EBV infection and the development of EBV-associated diseases. The EBV gB protein is essential for virus entry into B cells and epithelial cells and is thus a target antigen for vaccine development. Understanding T cell responses to gB is important for subunit vaccine design. Herein, we comprehensively characterized T cell responses to full-length gB. Our results expand the available gB epitopes and HLA restrictions, particularly those common in Asian populations. Furthermore, we showed that gB-specific CD8+ T cells inhibit B cell transformation ex vivo and that gB-specific CD8+ T cell responses in vivo may be associated with intermittent EBV reactivation in asymptomatic viral carriers. These gB epitopes are highly conserved among geographically separated EBV strains. Precisely mapped and conserved T cell epitopes may contribute to immune monitoring and to the development of a gB subunit vaccine.

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Section: Discussionmentioning

confidence: 99%

T Cell Epitope Screening of Epstein-Barr Virus Fusion Protein gB

Chen

Zhang

et al. 2021

J Virol

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“…e global incidence of the disease is increasing year by year, about 3-5/1000 person-year, with a recurrence rate of 12/ 1000 person-year [47,49]. Antiviral drugs effective against HZ showed no improvement in the relief of PHN, and so far, there is no satisfactory treatment for PHN [50,51], so researchers and doctors can only recommend shingles vaccine for the elderly to reduce HZ and PHN [52,53], while there has been no clear report on the effectiveness of vaccination in patients with severe immunodeficiency disease [54,55]. erefore, to explore the effective treatment of HZ and PHN is still the direction of the efforts of scholars.…”

Section: Discussionmentioning

confidence: 99%

Moxibustion for Herpes Zoster and Postherpetic Neuralgia: A Meta‐Analysis

Huang

Cheng

et al. 2021

Complexity

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Background. Herpes zoster (HZ) is a disease that mainly causes severe segmental neuralgia and vesicles after infection with herpes zoster virus (VZV). At the same time, more than 9 to 34 percent of patients have postherpetic neuralgia (PHN) present with chronic pain for months or even years. Moxibustion has been used to treat herpes zoster and postherpetic neuralgia for many years; however, there has been no comprehensive study to evaluate the efficacy and safety of moxibustion in the treatment of herpes zoster and postherpetic neuralgia. More studies evaluated the combined effects of acupuncture and moxibustion. Therefore, the purpose of this systematic review is to evaluate their efficacy and safety, so as to provide an evidence-based basis for the clinical application of moxibustion in the treatment of HZ and PHN. Method. The literature search was conducted in nine Chinese and English databases, and randomized controlled trials were pooled from their inceptions to June 2020. The included literature was screened, and data were extracted. RevMan 5.3 software and Stata software were used for statistical analysis. The primary outcome was the total effect. The secondary outcomes include VAS, NRS, and time of analgesia. Outcomes. From a total of 1957 identified studies, 31 were included in analysis (N = 2334 cases). 31 RCTs contained the experimental sample of 1185 cases and the control sample of 1149 cases reported efficiency of different moxibustions in the treatment of herpes zoster, statistical heterogeneity inspection without heterogeneity. So, we used the fixed-effects model, merge effect quantity OR = 3.89 (95% CI: 2.88∼5.25), Z = 8.86, and it suggested sample merger analysis was statistically significant. Also, the moxibustion, compared to other methods in the treatment of herpes zoster and herpes zoster neuralgia efficiency, increased significantly. The VAS scales, WMD = 1.69 (95% CI: 1.17∼2.22), and the time of analgesia, WMD = 2.41 (95% CI: 3.26∼1.73), indicated that moxibustion surpassed others in the relief of pain. NRS was just reported in one study. It was not statistically significant. There was no significant difference in adverse effects OR = 0.61 (95% CI: 0.33∼1.13), Z = 1.56 ( P = 0.12). Conclusion. Moxibustion has obvious advantages over other therapies in the treatment of HZ and PHN. However, due to the obvious publication bias, the interpretation of the results should be cautious, and more rigorous randomized controlled clinical studies should be included to further confirm the results in the future.

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“…VZV-specific T-cell responses are greater in response to the recombinant subunit vaccine than to the LAVs, whereas cytotoxic responses by CD8+ T cells and effector T cells are greater in response to the LAVs (43). Because IL-2 and IFN- are important in VZV-specific CMI, they have been analyzed in context of the vaccines.…”

Section: Herpes Zoster Vaccines and Immune Responsementioning

confidence: 99%

Immune Responses to Varicella Zoster Virus and Effective Vaccines

Lee¹,

Kim²,

Hong³

et al. 2021

jbv

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Varicella zoster virus (VZV) causes two distinct diseases, varicella (chickenpox) during primary infection, and herpes zoster (shingles) resulting from reactivation. The purpose of this review is to summarize the present understanding of VZV and the associated immune response, as well as to discuss available vaccines. VZV infection induces both innate and adaptive immune responses, especially an antigen-specific adaptive immune response, which activates humoral immunity and cell-mediated immunity (CMI). Reactivation of VZV can occur when the CMI of latent VZV is reduced, leading to herpes zoster. After VZV infection, natural killer (NK) cells modulate antigen presentation and the production of IFN-, an important activator of macrophages. IFN- is produced by NK cells and CD4 Th1/CD8 cytotoxic T lymphocytes. The T cell-mediated immune response is an important factor influencing VZV reactivation and herpes zoster, with herpes zoster being associated with reduced levels of VZV-specific T cells. Since the VZV-specific T cell population gradually declines with age, herpes zoster particularly affects the elderly. There are two types of zoster vaccines: live-attenuated and recombinant subunit. However, recombinant vaccines generally have poor immunogenicity when administered alone and require an adjuvant. Therefore, effective adjuvants are needed that especially promote cell-mediated immune responses. Various adjuvants have been developed, many of which enhance T cell immunity more than antibody-based humoral immunity. The information presented in this review may serve as a reference for future VZV immunology studies.

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A novel nonlive, adjuvanted herpes zoster subunit vaccine: a report on the emerging clinical data and safety profile

Cited by 11 publications

References 59 publications

T Cell Epitope Screening of Epstein-Barr Virus Fusion Protein gB

T Cell Epitope Screening of Epstein-Barr Virus Fusion Protein gB

Moxibustion for Herpes Zoster and Postherpetic Neuralgia: A Meta‐Analysis

Immune Responses to Varicella Zoster Virus and Effective Vaccines

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