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- Oostvogels, Lidia, et al.
(författare)
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Medical conditions at enrollment do not impact efficacy and safety of the adjuvanted recombinant zoster vaccine : a pooled post-hoc analysis of two parallel randomized trials
- 2019
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Ingår i: Human Vaccines & Immunotherapeutics. - : Informa UK Limited. - 2164-5515 .- 2164-554X. ; 15:12, s. 2865-2872
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Tidskriftsartikel (refereegranskat)abstract
- In two pivotal efficacy studies (ZOE-50; ZOE-70), the adjuvanted recombinant zoster vaccine (RZV) demonstrated >90% efficacy against herpes zoster (HZ). Adults aged >= 50 or >= 70 years (ZOE-50 [NCT01165177]; ZOE-70 [NCT01165229]) were randomized to receive 2 doses of RZV or placebo 2 months apart. Vaccine efficacy and safety were evaluated post-hoc in the pooled (ZOE-50/70) population according to the number and type of selected medical conditions present at enrollment. At enrollment, 82.3% of RZV and 82.7% of placebo recipients reported >= 1 of the 15 selected medical conditions. Efficacy against HZ ranged from 84.5% (95% Confidence Interval [CI]: 46.4-97.1) in participants with respiratory disorders to 97.0% (95%CI: 82.3-99.9) in those with coronary heart disease. Moreover, efficacy remained >90% irrespective of the number of selected medical conditions reported by a participant. As indicated by the similarity of the point estimates, this post-hoc analysis suggests that RZV efficacy remains high in all selected medical conditions, as well as with increasing number of medical conditions. No safety concern was identified by the type or number of medical conditions present at enrollment.
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- Rumke, Hans C., et al.
(författare)
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Selection of an adjuvant for seasonal influenza vaccine in elderly people : modelling immunogenicity from a randomized trial
- 2013
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Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 13, s. 348-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Improved influenza vaccines are needed to reduce influenza-associated complications in older adults. The aim of this study was to identify the optimal formulation of adjuvanted seasonal influenza vaccine for use in elderly people. Methods: This observer-blind, randomized study assessed the optimal formulation of adjuvanted seasonal influenza vaccine based on immunogenicity and safety in participants aged >= 65 years. Participants were randomized (similar to 200 per group) to receive one dose of non-adjuvanted vaccine or one of eight formulations of vaccine formulated with a squalene and tocopherol oil-in-water emulsion-based Adjuvant System (AS03(C), AS03(B) or AS03(A), with 2.97, 5.93 and 11.86 mg tocopherol, respectively) together with the immunostimulant monophosphoryl lipid A (MPL, doses of 0, 25 or 50 mg). Hemagglutination-inhibition (HI) antibody responses and T-cell responses were assessed on Day 0 and 21 days post-vaccination. The ratio of HI-based geometric mean titers in adjuvanted versus non-adjuvanted vaccine groups were calculated and the lower limit of the 90% confidence interval was transformed into a desirability index (a value between 0 and 1) in an experimental domain for each vaccine strain, and plotted in relation to the AS03 and MPL dose combination in the formulation. This model was used to assess the optimal formulation based on HI antibody titers. Reactogenicity and safety were also assessed. The immunogenicity and safety analyses were used to evaluate the optimal formulation of adjuvanted vaccine. Results: In the HI antibody-based model, an AS03 dose-response was evident; responses against the A/H1N1 and A/H3N2 strains were higher for all adjuvanted formulations versus non-adjuvanted vaccine, and for the AS03(A)-MPL25, AS03(B)-MPL25 and AS03(B)-MPL50 formulations against the B strain. Modelling using more stringent criteria (post hoc) showed a clear dose-range effect for the AS03 component against all strains, whereas MPL showed a limited effect. Higher T-cell responses for adjuvanted versus non-adjuvanted vaccine were observed for all except two formulations (AS03(C) and AS03(B)-MPL25). Reactogenicity increased with increasing AS03 dosage, and with MPL. No safety concerns were raised. Conclusions: Five formulations containing AS03(A) or AS03(B) were identified as potential candidates to improve immune responses to influenza vaccination; AS03(B) without MPL showed the best balance between improved immunogenicity and acceptable reactogenicity.
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- 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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