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Evaluation of glycoprotein E subunit and live attenuated varicella-zoster virus vaccines formulated with a single-strand RNA-based adjuvant.

ABSTRACT: INTRODUCTION:Varicella-zoster virus (VZV), a human alphaherpesvirus 3, elicits both chickenpox and shingles and/or postherpetic neuralgia. A live attenuated vaccine (LAV) and glycoprotein E (gE) subunit vaccine were developed to prevent VZV-induced diseases. We recently reported that single-strand RNA (ssRNA) based on the intergenic region of the internal ribosome entry site of cricket paralysis virus (CrPV) is an effective adjuvant for protein-based and virus-like particle-based vaccines. Here, Chinese hamster ovary expression system and an LAV from Oka/SK strains. METHODS:We appraised the adjuvant effect of the same CrPV ssRNA encoding the gE gene formulated in the two vaccines using VZV-primed C57BL/6 mice and guinea pigs. Humoral immunity and cell-mediated immunity were assessed by enzyme-linked immunosorbent assay (ELISA) and ELISPOT in gE subunit vaccine and by ELISA and fluorescent antibody to membrane antigen in LAV. RESULTS:The gE subunit vaccine-induced gE-specific antibodies and CD4+ T-cell responses (indicated by interferon-? [IFN-?] and interleukin-2 secretion) in the ssRNA-based adjuvant containing the VZV gE gene. Therefore, an ssRNA adjuvant combined with gE antigen can trigger the innate immune response and induce an adaptive immune response to ultimately activate humoral and cell-mediated responses. VZV LAV could also induce VZV-specific antibodies and IFN-? stimulated by LAV, whereas the effect of ssRNA as a vaccine adjuvant could not be confirmed. However, the ssRNA adjuvant increased VZV-specific neutralizing antibody response. CONCLUSIONS:Taken together, these results highlight that the gE subunit vaccine and LAV developed in this study can be functional VZV vaccines, and ssRNAs appear to function better as adjuvants in a subunit vaccine than in an LAV.

SUBMITTER: Lee SJ

PROVIDER: S-EPMC7212201 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Evaluation of glycoprotein E subunit and live attenuated varicella-zoster virus vaccines formulated with a single-strand RNA-based adjuvant.

Lee Su Jeen SJ Park Hyo-Jung HJ Ko Hae Li HL Lee Jung Eun JE Lee Hyun Joo HJ Kim Hun H Nam Jae-Hwan JH

Immunity, inflammation and disease 20200313 2

<h4>Introduction</h4>Varicella-zoster virus (VZV), a human alphaherpesvirus 3, elicits both chickenpox and shingles and/or postherpetic neuralgia. A live attenuated vaccine (LAV) and glycoprotein E (gE) subunit vaccine were developed to prevent VZV-induced diseases. We recently reported that single-strand RNA (ssRNA) based on the intergenic region of the internal ribosome entry site of cricket paralysis virus (CrPV) is an effective adjuvant for protein-based and virus-like particle-based vaccine ...[more]

PMID: 32167678

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Project description:Two herpes zoster (HZ) vaccines licensed in the United States are recommended by the Advisory Committee on Immunization Practices (ACIP): (i) live-attenuated vaccine (ZVL) using vOka strain varicella-zoster virus (VZV) and (ii) recombinant adjuvanted vaccine (RZV) containing recombinant varicella-zoster virus (VZV) glycoprotein E (gE). Two phase 3 clinical trials of RZV led the Advisory Committee on Immunization Practices (ACIP) to recommend it with preferred status. VZV T cell-mediated immunity (CMI), but not humoral immunity, is considered essential for protection against HZ. Published studies of humoral immunity focused on VZV-specific IgG concentration. To complement reports comparing the CMI responses to these vaccines, we compared humoral responses in ZVL and RZV recipients, emphasizing functional qualities (avidity and neutralization). Baseline avidities to a VZV glycoprotein mixture (gp) were near the upper limit of detection, but avidity to gE was much lower. Small increases in gp avidity were observed for both RZV and ZVL vaccination (19 and 12 avidity index units [AIU], respectively). RZV boosted both gE avidity and VZV neutralizing antibody significantly more than ZVL (mean gE avidity boost, 47 AIU versus 22 AIU; mean neutralizing antibody boost, 22-fold versus 8-fold). Increases in neutralizing antibodies strongly correlated with gE avidity increases (r = 0.5) and moderately with gp avidity increases (r = 0.23). After 1 year, 81% of RZV recipients and only 18% of ZVL recipients retained >50% of their peak avidity boosts. These results are consistent with the CMI responses to these vaccines: RZV responses are skewed to long-term memory, whereas ZVL preferentially induces transient effector responses.IMPORTANCE These observations further distinguish the immunogenicity and duration of the immune response of the two vaccines. In addition, measurements of functional humoral immunity (IgG avidity and neutralizing antibody) in response to zoster immunization, alone or combined with other immune markers, might contribute to practical in vitro correlates of protection. Combined with previous observations of the cell-mediated response to these vaccines, this study suggests that vaccine development will benefit from more expansive and granular assessments of acquired immunity during early phase 1 immunogenicity trials.

Project description:BACKGROUND:The newly registered adjuvanted herpes zoster subunit vaccine (HZ/su) has a higher efficacy than the available live-attenuated vaccine (ZVL). National decision-makers soon need to decide whether to introduce HZ/su or to prefer HZ/su above ZVL. METHODS:Using a Markov model with a decision tree, we conducted a cost-effectiveness analysis of vaccination with HZ/su (two doses within 2?months) or zoster vaccine live (ZVL) (single dose, or single dose with a booster after 10?years) for cohorts of 50-, 60-, 70- or 80-year-olds in the Netherlands. The model was parameterized using vaccine efficacy data from randomized clinical trials and up-to-date incidence, costs and health-related quality of life data from national datasets. We used a time horizon of 15?years, and the analysis was conducted from the societal perspective. RESULTS:At a coverage of 50%, vaccination with two doses of HZ/su was estimated to prevent 4335 to 10,896 HZ cases, depending on the cohort age. In comparison, this reduction was estimated at 400-4877 for ZVL and 427-6466 for ZVL with a booster. The maximum vaccine cost per series of HZ/su to remain cost-effective to a willingness-to-pay threshold of €20,000 per quality-adjusted life year (QALY) gained ranged from €109.09 for 70-year-olds to €63.68 for 50-year-olds. The cost-effectiveness of ZVL changed considerably by age, with corresponding maximum vaccine cost per dose ranging from €51.37 for 60-year-olds to €0.73 for 80-year-olds. Adding a ZVL booster after 10?years would require a substantial reduction of the maximum cost per dose to remain cost-effective as compared to ZVL single dose. Sensitivity analyses on the vaccine cost demonstrated that there were scenarios in which vaccination with either HZ/su (two doses), ZVL single dose or ZVL + booster could be the most cost-effective strategy. CONCLUSIONS:A strategy with two doses of HZ/su was superior in reducing the burden of HZ as compared to a single dose or single dose + booster of ZVL. Both vaccines could potentially be cost-effective to a conventional Dutch willingness-to-pay threshold for preventive interventions. However, whether HZ/su or ZVL would be the most cost-effective alternative depends largely on the vaccine cost.

Dataset Information

Evaluation of glycoprotein E subunit and live attenuated varicella-zoster virus vaccines formulated with a single-strand RNA-based adjuvant.

Publications

Evaluation of glycoprotein E subunit and live attenuated varicella-zoster virus vaccines formulated with a single-strand RNA-based adjuvant.

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