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- López-Fauqued, M., et al.
(författare)
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Safety profile of the adjuvanted recombinant zoster vaccine : Pooled analysis of two large randomised phase 3 trials
- 2019
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Ingår i: Vaccine. - : Elsevier Ltd. - 0264-410X .- 1873-2518. ; 37:18, s. 2482-2493
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Tidskriftsartikel (refereegranskat)abstract
- Background: The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies. Methods: Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30 days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12 months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period. Results: Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race. Conclusions: No safety concerns arose, supporting the favorable benefit-risk profile of RZV. © 2019 GlaxoSmithKline Biologicals SA
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- Chlibek, Roman, et al.
(författare)
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Long-term immunogenicity and safety of an investigational herpes zoster subunit vaccine in older adults
- 2016
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 34:6, s. 863-868
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Tidskriftsartikel (refereegranskat)abstract
- Background: An investigational subunit vaccine containing the varicella-zoster virus (VZV) glycoprotein E (gE) and the AS01(B) adjuvant system is being evaluated for the prevention of herpes zoster (HZ) in older adults. A phase II trial evaluating different formulations of this vaccine (containing 25 mu g, 50 mu g, or 100 mu g gE) was conducted in adults >= 60 years of age and showed that all formulations elicited robust cellular and humoral immune responses for up to 3 years after vaccination. In this follow-up study in subjects who received two doses of the 50 mu g gE/AS01(B) formulation (HZ/su), we assessed the persistence of the immune responses for up to 6 years after vaccination. Methods: This phase II, open-label, multicenter, single-group trial conducted in the Czech Republic, Germany, Sweden, and the Netherlands followed 129 subjects who had received two doses (2 months apart) of HZ/su during the initial trial. Vaccine-induced immune responses (frequencies of gE-specific CD4(+) T cells expressing >= 2 activation markers and serum anti-gE antibody concentrations) were evaluated at 48, 60, and 72 months after the first HZ/su dose. Results: Six years after vaccination with HZ/su, gE-specific cell-mediated immune responses and anti-gE antibody concentrations had decreased by 20-25% from month 36, but remained higher than the prevaccination values. At month 72, the gE-specific cell-mediated immune response was 3.8 times higher than the prevaccination value (477.3 vs. 119.4 activated gE-specific CD4(+) T cells per 10(6) cells), and the anti-gE antibody concentration was 7.3 times higher than the prevaccination value (8159.0 vs. 1121.3 mIU/mL). No vaccine-related serious adverse events were reported between months 36 and 72. Conclusions: gE-specific cellular and humoral immune responses persisted for 6 years after two-dose vaccination with HZ/su in healthy older adults. No safety concerns were identified.
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- Chlibek, Roman, et al.
(författare)
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Safety and immunogenicity of three different formulations of an adjuvanted varicella-zoster virus subunit candidate vaccine in older adults : A phase II, randomized, controlled study
- 2014
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 32:15, s. 1745-1753
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study investigated the safety and immunogenicity of different formulations and schedules of a candidate subunit herpes zoster vaccine containing varicella-zoster virus glycoprotein E (gE) with or without the adjuvant system ASO1(B). Methods: In this phase II, single-blind, randomized, controlled study, adults aged >= 60 years (N = 714) received one dose of 100 mu g gE/AS01(B), two doses, two months apart, of 25, 50, or 100 mu g gE/AS01(B), or two doses of unadjuvanted 100 mu g gE/saline. Frequencies of CD4(+) T cells expressing >= 2 activation markers following induction with gE were measured by intracellular cytokine staining and serum anti-gE antibody concentrations by ELISA. Results: Frequencies of gE-specific CD4(+) T cells were >3-fold higher after two doses of all gE/AS01(B) formulations than after one dose of 100 mu g gE/AS01(B) or two doses of 100 mu g gE/saline. Frequencies were comparable after two doses of 25, 50, or 100 mu g gE/AS01g. Serum anti-gE antibody concentrations were comparable after two doses of 50 or 100 mu g gE/AS01(B) and higher than in the other groups. Immune responses persisted for at least 36 months. Reactogenicities of all gE/AS01(B) formulations were similar but greater than with gE/saline. Conclusions: The three formulations of gE/AS01(B) were immunogenic and well tolerated in adults aged >= 60 years. Two vaccinations with gE/AS01(B) induced higher immune responses than one and the dose of gE impacted humoral but not cellular immune responses (NCT00434577).
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| 5. |
- Cunningham, Anthony L., et al.
(författare)
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Immune Responses to a Recombinant Glycoprotein E Herpes Zoster Vaccine in Adults Aged 50 Years or Older
- 2018
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 217:11, s. 1750-1760
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Tidskriftsartikel (refereegranskat)abstract
- Background. The herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01(B) Adjuvant System, was highly efficacious in preventing herpes zoster in the ZOE-50 and ZOE-70 trials. We present immunogenicity results from those trials. Methods. Participants (ZOE-50: >= 50; ZOE-70: >= 70 years of age) received 2 doses of HZ/su or placebo, 2 months apart. Serum anti-gE antibodies and CD4 T cells expressing >= 2 of 4 activation markers assessed (CD4(2+)) after stimulation with gE-peptides were measured in subcohorts for humoral (n = 3293) and cell-mediated (n = 466) immunogenicity. Results. After vaccination, 97.8% of HZ/su and 2.0% of placebo recipients showed a humoral response. Geometric mean anti-gE antibody concentrations increased 39.1-fold and 8.3-fold over baseline in HZ/su recipients at 1 and 36 months post-dose 2, respectively. A gE-specific CD4(2+) T-cell response was shown in 93.3% of HZ/su and 0% of placebo recipients. Median CD42+ T-cell frequencies increased 24.6-fold (1 month) and 7.9-fold (36 months) over baseline in HZ/su recipients and remained >= 5.6-fold above baseline in all age groups at 36 months. The proportion of CD4 T cells expressing all 4 activation markers increased over time in all age groups. Conclusions. Most HZ/su recipients developed robust immune responses persisting for 3 years following vaccination.
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| 6. |
- Schwarz, Tino F., et al.
(författare)
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Persistence of immune response to an adjuvanted varicella-zoster virus subunit vaccine for up to year nine in older adults
- 2018
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Ingår i: Human Vaccines & Immunotherapeutics. - : TAYLOR & FRANCIS INC. - 2164-5515 .- 2164-554X. ; 14:6, s. 1370-1377
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Tidskriftsartikel (refereegranskat)abstract
- Background: In adults aged 60years, two doses of the herpes zoster subunit vaccine (HZ/su; 50 mu g varicella-zoster virus glycoprotein E [gE] and AS01(B) Adjuvant System) elicited humoral and cell-mediated immune responses persisting for at least six years. We assessed immunogenicity nine years post-initial vaccination.Methods: This open extension study (NCT02735915) followed 70 participants who received two HZ/su doses in the initial trial (NCT00434577). Blood samples to assess the cellular (intracellular cytokine staining) and humoral (ELISA) immunity were taken at year nine post-initial vaccination.Results: Participants' mean age at dose 1 was 72.3years. The fold increases over pre-vaccination in the mean frequency of gE-specific CD4+ T-cells expressing 2 activation markers plateaued from year four post-dose 1 until year nine. Anti-gE antibody geometric mean concentrations plateaued and remained above pre-vaccination levels from year four onwards. Immunogenicity at year nine was similar across age strata (60-69, 70years) and confirmed statistical prediction model results using data for up to year six. Further modeling using all data up to year nine predicted immune responses would remain above the pre-vaccination level up to year 15.Conclusion: In adults aged 60years, HZ/su-induced immunogenicity remained above pre-vaccination levels for at least nine years post-initial vaccination.Summary: After vaccination with HZ/su, both cell mediated and humoral immunity remained above pre-vaccination levels up to year 9 regardless of age group. Immune responses are predicted to remain above baseline up to 15years post initial vaccination.
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