Serological and T Cell Responses After Varicella Zoster Virus Vaccination in HIV-Positive Patients Undergoing Renal Dialysis

Righi, Elda; Carnelutti, Alessia; Rosa, Alessandro La; Sartor, Assunta; Tulissi, P.; Gallo, Tolinda; Ivaldi, Federico; Bassetti, Matteo

doi:10.1089/vim.2018.0112

Cited by 2 publications

(4 citation statements)

References 24 publications

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“…Shingrix has shown increased efficacy in elderly and other groups as compared to the Zostavax vaccine (27,54,66). The reasons for this remarkable difference may involve intrinsic differences in the quality and durability of the responses elicited, also perhaps because of inclusion of the AS01B adjuvant.…”

Section: Discussionmentioning

confidence: 99%

“…The recombinant VZV gE protein is co-formulated with the novel ASB01 adjuvant to induce both a strong CD4+ T cell and gE-specific antibody response (6,27). VZV-specific CD4+ T cell responses are associated with positive vaccine outcomes (20,54,59,62). The reasons for the remarkable difference in Shingrix efficacy may involve a capacity for eliciting a stronger and/or more focused response against the gE antigen, a broader epitope repertoire or an intrinsic difference in the quality and durability of the responses elicited.…”

Section: Introductionmentioning

confidence: 99%

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Identification and Characterization of CD4 ⁺ T Cell Epitopes after Shingrix Vaccination

Voic

Vries

Sidney

et al. 2020

J Virol

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Infections with varicella zoster virus (VZV) are associated with a range of clinical manifestations. Primary infection with VZV causes chicken pox. The virus remains latent in neurons and it can reactivate later in life causing herpes zoster (HZ). Two different vaccines have been developed to prevent HZ, one based on a live attenuated VZV strain (Zostavax) and the other on adjuvanted gE recombinant protein (Shingrix). While Zostavax efficacy wanes with age, Shingrix protection retains its efficacy in elderly subjects (80 years of age and beyond). In this context, it is of much interest to understand if there is a role for T cell immunity in differential clinical outcome, and if there is a correlate of protection between T cell immunity and Shingrix efficacy. In this study, we characterized Shingrix specific ex vivo CD4 T cell responses in the context of natural exposure and HZ vaccination using pools of predicted epitopes. We show that T cell reactivity following natural infection and Zostavax vaccination dominantly targets non-structural proteins (NS), while Shingrix vaccination redirects dominant reactivity to target gE. We mapped the gE-specific responses following Shingrix vaccination to 89 different gE epitopes, 34 of which accounted for 80% of the response. Using antigen presentation assays and single HLA molecule transfected lines, we experimentally determined HLA restrictions for 94 different donor/peptide combinations. Finally, we used our results as a training set to assess strategies to predict restrictions based on measured or predicted HLA binding and the corresponding HLA types of responding subjects. Importance Understanding the T cell profile associated with the protection observed in elderly vaccinees following Shingrix vaccination is relevant to the general definition of correlates of vaccine efficacy. Our study enables these future studies by clarifying patterns of immunodominance associated with Shingrix vaccination, as opposed to natural infection or Zostavax vaccination. Identification of epitopes recognized by Shingrix-induced CD4 T cells and their associated HLA restrictions enables the generation of tetrameric staining reagents and, more broadly, the capability to characterize specificity, magnitude and phenotype of VZV specific T cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification and Characterization of CD4 ⁺ T Cell Epitopes after Shingrix Vaccination

Voic

Vries

Sidney

et al. 2020

J Virol

View full text Add to dashboard Cite

show abstract

“…Shingrix has shown increased efficacy in elderly and other groups as compared to the Zostavax vaccine (19,42,54). The reasons for this remarkable difference may involve intrinsic differences in the quality and durability of the responses elicited, also perhaps because of inclusion of the AS01 b adjuvant.…”

Section: Discussionmentioning

confidence: 99%

“…T cell and gE-specific antibody response (4,19). VZV-specific CD4+ T cell responses are associated with positive vaccine outcomes (15,42,48,51). The reasons for the remarkable difference in Shingrix efficacy may involve a capacity for eliciting a stronger and/or more focused response against the gE antigen, a broader epitope repertoire or an intrinsic difference in the quality and durability of the responses elicited.…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of CD4+ T cell epitopes after Shingrix vaccination

Voic¹,

Vries

Sidney³

et al. 2020

Preprint

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Infections with varicella zoster virus (VZV), a member of the Herpesviridae family, are associated with a range of clinical manifestations. Primary infection with VZV causes chicken pox, and due to the virus’s capacity to remain latent in neurons, it can reactivate later in life causing herpes zoster (HZ), also known as shingles. Two different licensed vaccines are available to prevent HZ, either based on a live attenuated VZV strain (Zostavax) or on adjuvanted gE recombinant protein (Shingrix). While Zostavax efficacy wanes with age, Shingrix protection retains its efficacy in elderly subjects (80 years of age and beyond). In this context, studies to evaluate the potential role of T cell immunity as a correlate of protection and Shingrix efficacy are of interest. In this study, we characterized Shingrix specific ex vivo CD4 T cell responses in the context of natural exposure and HZ vaccination using pools of predicted epitopes. We show that T cell reactivity following natural infection and Zostavax vaccination dominantly targets non-structural proteins, while Shingrix vaccination redirects dominant reactivity to target gE. We mapped the gE-specific responses following Shingrix vaccination to 89 different gE epitopes, 34 of which accounted for 80% of the response. Using antigen presentation assays and single HLA molecule transfected lines, we experimentally determined HLA restrictions for 94 different donor/peptide combinations. Finally, we used our results as a training set to assess strategies to predict restrictions based on measured or predicted HLA binding and the corresponding HLA types of responding subjects.ImportanceUnderstanding the T cell profile associated with the protection observed in elderly vaccines following Shingrix vaccination is relevant to the general definition of correlates of vaccine efficacy. Our study enables these future studies by clarifying patterns of immunodominance associated with Shingrix vaccination, as opposed to natural infection or Zostavax vaccination. Identification of epitopes recognized by Shingrix-induced CD4 T cells vaccinees, and their associated HLA restrictions, enables the generation of tetrameric staining reagents, and more broadly the capability to characterize specificity, magnitude and phenotype of VZV specific T cells.

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Serological and T Cell Responses After Varicella Zoster Virus Vaccination in HIV-Positive Patients Undergoing Renal Dialysis

Cited by 2 publications

References 24 publications

Identification and Characterization of CD4 ⁺ T Cell Epitopes after Shingrix Vaccination

Identification and Characterization of CD4 ⁺ T Cell Epitopes after Shingrix Vaccination

Identification and characterization of CD4+ T cell epitopes after Shingrix vaccination

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Serological and T Cell Responses After Varicella Zoster Virus Vaccination in HIV-Positive Patients Undergoing Renal Dialysis

Cited by 2 publications

References 24 publications

Identification and Characterization of CD4 + T Cell Epitopes after Shingrix Vaccination

Identification and Characterization of CD4 + T Cell Epitopes after Shingrix Vaccination

Identification and characterization of CD4+ T cell epitopes after Shingrix vaccination

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Identification and Characterization of CD4 ⁺ T Cell Epitopes after Shingrix Vaccination

Identification and Characterization of CD4 ⁺ T Cell Epitopes after Shingrix Vaccination