Comparative Immune Responses to Licensed Herpes Zoster Vaccines

Weinberg, Adriana; Kroehl, Miranda; Johnson, Michael J.; Hammes, Andrew; Reinhold, Dominik; Lang, Nancy; Levin, Myron J.

doi:10.1093/infdis/jiy383

Cited by 38 publications

(30 citation statements)

References 31 publications

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“…When immune responses to ZVL and RZV were compared in participants aged 50-85, both VZV and gE-specific T cells were more frequent after RZV administration; gE-specific CD4 and CD8 effector and memory T cell responses were >10-fold higher after RZV,6768 and the peak responses in RZV recipients approximately predicted their subsequent persistence. gE-specific T cell responses to RZV have remained above baseline levels for at least nine years 54697071.…”

Section: Vaccines For Herpes Zostermentioning

confidence: 97%

Vaccines for older adults

Cunningham

McIntyre

Subbarao

et al. 2021

BMJ

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The proportion of the global population aged 65 and older is rapidly increasing. Infections in this age group, most recently with SARS-CoV-2, cause substantial morbidity and mortality. Major improvements have been made in vaccines for older people, either through the addition of novel adjuvants—as in the new recombinant zoster vaccine and an adjuvanted influenza vaccine—or by increasing antigen concentration, as in influenza vaccines. In this article we review improvements in immunization for the three most important vaccine preventable diseases of aging. The recombinant zoster vaccine has an efficacy of 90% that is minimally affected by the age of the person being vaccinated and persists for more than four years. Increasing antigen dose or inclusion of adjuvant has improved the immunogenicity of influenza vaccines in older adults, although the relative effectiveness of the enhanced influenza vaccines and the durability of the immune response are the focus of ongoing clinical trials. Conjugate and polysaccharide pneumococcal vaccines have similar efficacy against invasive pneumococcal disease and pneumococcal pneumonia caused by vaccine serotypes in older adults. Their relative value varies by setting, depending on the prevalence of vaccine serotypes, largely related to conjugate vaccine coverage in children. Improved efficacy will increase public confidence and uptake of these vaccines. Co-administration of these vaccines is feasible and important for maximal uptake in older people. Development of new vaccine platforms has accelerated following the arrival of SARS-CoV-2, and will likely result in new vaccines against other pathogens in the future.

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Section: Vaccines For Herpes Zostermentioning

confidence: 97%

Vaccines for older adults

Cunningham

McIntyre

Subbarao

et al. 2021

BMJ

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“…However, the present knowledge regarding B cell responses to gE, following vaccination with any of the two HZ vaccines, is sparse. It has been reported that Zostavax ® induces antibodies, primarily against gE, as determined by clonal expansion of B cells [33], but no such data are available for the recombinant subunit vaccine, although it elicits a stronger gE-specific Th1 memory response compared to the live attenuated vaccine [9,10].…”

Section: Discussionmentioning

confidence: 99%

“…When both vaccines were administered simultaneously, there was no increase either in cellular or humoral responses to gE, as compared to giving the recombinant vaccine alone [6]. Recent comparative studies have highlighted that the superior efficacy of the recombinant subunit vaccine can be explained by its ability to generate a higher T cell memory response compared to the live vaccine [9,10]. Still, the question remains: How can a vaccine based only on one single glycoprotein outcompete a live virus (although attenuated) vaccine that actually results in an active virus infection?…”

Section: Introductionmentioning

confidence: 99%

Recombinant Glycoprotein E of Varicella Zoster Virus Contains Glycan-Peptide Motifs That Modulate B Cell Epitopes into Discrete Immunological Signatures

Nordén

Nilsson

Samuelsson

et al. 2019

IJMS

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A recombinant subunit vaccine (Shingrix®) was recently licensed for use against herpes zoster. This vaccine is based on glycoprotein E (gE) of varicella zoster virus (VZV), the most abundantly expressed protein of VZV, harboring sites for N- and O-linked glycosylation. The subunit vaccine elicits stronger virus-specific CD4+ T cell response as well as antibody B cell response to gE, compared to the currently used live attenuated vaccine (Zostavax®). This situation is at variance with the current notion since a live vaccine, causing an active virus infection, should be far more efficient than a subunit vaccine based on only one single viral glycoprotein. We previously found gE to be heavily glycosylated, not least by numerous clustered O-linked glycans, when it was produced in human fibroblasts. However, in contrast to Zostavax®, which is produced in fibroblasts, the recombinant gE of Shingrix® is expressed in Chinese hamster ovary (CHO) cells. Hence, the glycan occupancy and glycan structures of gE may differ considerably between the two vaccine types. Here, we aimed at (i) defining the glycan structures and positions of recombinant gE and (ii) identifying possible features of the recombinant gE O-glycosylation pattern contributing to the vaccine efficacy of Shingrix®. Firstly, recombinant gE produced in CHO cells (“Shingrix situation”) is more scarcely decorated by O-linked glycans than gE from human fibroblasts (“Zostavax situation”), with respect to glycan site occupancy. Secondly, screening of immunodominant B cell epitopes of gE, using a synthetic peptide library against serum samples from VZV-seropositive individuals, revealed that the O-linked glycan signature promoted binding of IgG antibodies via a decreased number of interfering O-linked glycans, but also via specific O-linked glycans enhancing antibody binding. These findings may, in part, explain the higher protective efficacy of Shingrix®, and can also be of relevance for development of subunit vaccines to other enveloped viruses.

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“…Indeed, the highly efficacious new recombinant subunit HZ vaccine (Shingrix ® ) contains an adjuvanted form of VZV gE that was shown to elicit a robust humoral and cell-mediated immunity (Mo et al, 2002; James et al, 2018; Syed, 2018). In contrast, Zostavax TM induces a lower VZV-specific cell-mediated immunity including a reduced gE-specific memory T cell responses compared to Shingrix ® (Levin et al, 2018; Weinberg et al, 2018).…”

Section: The Important Role Of T Cells In the Establishment And Maintmentioning

confidence: 91%

Varicella Virus-Host Interactions During Latency and Reactivation: Lessons From Simian Varicella Virus

Sorel

Messaoudi

2018

Front. Microbiol.

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Varicella zoster virus (VZV) is a neurotropic alphaherpesvirus and the causative agent of varicella (chickenpox) in humans. Following primary infection, VZV establishes latency in the sensory ganglia and can reactivate to cause herpes zoster, more commonly known as shingles, which causes significant morbidity, and on rare occasions mortality, in the elderly. Because VZV infection is highly restricted to humans, the development of a reliable animal model has been challenging, and our understanding of VZV pathogenesis remains incomplete. As an alternative, infection of rhesus macaques with the homologous simian varicella virus (SVV) recapitulates the hallmarks of VZV infection and thus constitutes a robust animal model to provide critical insights into VZV pathogenesis and the host antiviral response. In this model, SVV infection results in the development of varicella during primary infection, generation of an adaptive immune response, establishment of latency in the sensory ganglia, and viral reactivation upon immune suppression. In this review, we discuss our current knowledge about host and viral factors involved in the establishment of SVV latency and reactivation as well as the important role played by T cells in SVV pathogenesis and antiviral immunity.

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Comparative Immune Responses to Licensed Herpes Zoster Vaccines

Abstract: NCT02114333.

Cited by 38 publications

References 31 publications

Vaccines for older adults

Vaccines for older adults

Recombinant Glycoprotein E of Varicella Zoster Virus Contains Glycan-Peptide Motifs That Modulate B Cell Epitopes into Discrete Immunological Signatures

Varicella Virus-Host Interactions During Latency and Reactivation: Lessons From Simian Varicella Virus

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