BACKGROUND: An investigational subunit vaccine containing the varicella-zoster virus (VZV) glycoprotein E (gE) and the AS01B 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 25μg, 50μg, or 100μg 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 50μg gE/AS01B 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. 1121.3mIU/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.

• Klíčová slova
• Glycoprotein E, Immunogenicity, NCT01295320, Persistence, Subunit vaccine, Varicella-zoster virus,
• MeSH
• buněčná imunita * MeSH
• CD4-pozitivní T-lymfocyty imunologie   MeSH
• fixní kombinace léků MeSH
• herpes zoster prevence a kontrola   MeSH
• humorální imunita * MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipid A aplikace a dávkování   analogy a deriváty   MeSH
• následné studie MeSH
• proteiny virového obalu imunologie   MeSH
• protilátky virové krev   MeSH
• saponiny aplikace a dávkování   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• subjednotkové vakcíny imunologie   terapeutické užití   MeSH
• vakcína proti pásovému oparu imunologie   terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• adjuvant system 01 MeSH Prohlížeč
• fixní kombinace léků MeSH
• lipid A MeSH
• proteiny virového obalu MeSH
• protilátky virové MeSH
• saponiny MeSH
• subjednotkové vakcíny MeSH
• vakcína proti pásovému oparu MeSH

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 AS01B. METHODS: In this phase II, single-blind, randomized, controlled study, adults aged ≥60years (N=714) received one dose of 100μggE/AS01B, two doses, two months apart, of 25, 50, or 100μggE/AS01B, or two doses of unadjuvanted 100μggE/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/AS01B formulations than after one dose of 100μggE/AS01B or two doses of 100μggE/saline. Frequencies were comparable after two doses of 25, 50, or 100μggE/AS01B. Serum anti-gE antibody concentrations were comparable after two doses of 50 or 100μggE/AS01B and higher than in the other groups. Immune responses persisted for at least 36 months. Reactogenicities of all gE/AS01B formulations were similar but greater than with gE/saline. CONCLUSIONS: The three formulations of gE/AS01B were immunogenic and well tolerated in adults aged ≥60years. Two vaccinations with gE/AS01B induced higher immune responses than one and the dose of gE impacted humoral but not cellular immune responses (NCT00434577).

• Klíčová slova
• Adjuvant, Herpes zoster, Vaccine, Varicella-zoster virus, gE,
• MeSH
• adjuvancia imunologická aplikace a dávkování   MeSH
• buněčná imunita * MeSH
• CD4-pozitivní T-lymfocyty imunologie   MeSH
• humorální imunita * MeSH
• imunologická odpověď na dávku MeSH
• jednoduchá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• očkovací schéma MeSH
• protilátky virové krev   MeSH
• senioři MeSH
• subjednotkové vakcíny škodlivé účinky   imunologie   terapeutické užití   MeSH
• vakcína proti pásovému oparu škodlivé účinky   imunologie   terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• adjuvancia imunologická MeSH
• protilátky virové MeSH
• subjednotkové vakcíny MeSH
• vakcína proti pásovému oparu MeSH

BACKGROUND: In adults aged ≥60 years, two doses of the herpes zoster subunit vaccine (HZ/su; 50 µg varicella-zoster virus glycoprotein E [gE] and AS01B 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 72.3 years. 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, ≥70 years) 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 ≥60 years, 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 15 years post initial vaccination.

• Klíčová slova
• herpes zoster, herpes zoster (shingles) vaccine, immunity, persistence, prediction modeling, prevention, subunit gE vaccine, varicella-zoster virus,
• MeSH
• časové faktory MeSH
• cytokiny analýza   MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipid A aplikace a dávkování   analogy a deriváty   MeSH
• následné studie MeSH
• protilátky virové krev   MeSH
• saponiny aplikace a dávkování   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• subjednotkové vakcíny aplikace a dávkování   imunologie   MeSH
• T-lymfocyty imunologie   MeSH
• vakcína proti pásovému oparu aplikace a dávkování   imunologie   MeSH
• virus varicella zoster imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• práce podpořená grantem MeSH
• Názvy látek
• AS01B adjuvant MeSH Prohlížeč
• cytokiny MeSH
• lipid A MeSH
• protilátky virové MeSH
• saponiny MeSH
• subjednotkové vakcíny MeSH
• vakcína proti pásovému oparu MeSH

BACKGROUND: An adjuvanted varicella-zoster virus glycoprotein E (gE) subunit vaccine candidate for herpes zoster is in development. In this trial we compared the safety, reactogenicity, and immunogenicity of the vaccine antigen combined with different adjuvant doses. METHODS: This was a phase II, observer-blind, randomized, multinational study. Adults ≥50 years old were randomized 4:4:2:1 to be vaccinated at months 0 and 2 with gE combined with a higher (AS01B) or lower (AS01E) dose adjuvant, unadjuvanted gE, or saline. Following each dose, solicited events were recorded for 7 days and unsolicited adverse events for 30 days. Serious adverse events were collected for 1 year. Cell-mediated and humoral immune responses were assessed at baseline and following each dose. RESULTS: No vaccine-related severe adverse events were reported. Solicited adverse events were generally mild to moderate and transient. For all gE-based vaccines, pain was the most common local symptom and fatigue the most common general symptom. Immune responses were significantly enhanced by AS01B and AS01E compared to unadjuvanted gE and were significantly stronger for gE/AS01B than for gE/AS01E. CONCLUSIONS: AS01 improved the immunogenicity of gE while retaining acceptable safety and reactogenicity profiles. The enhancement of gE-specific cellular and humoral responses was adjuvant dose dependent. CLINICAL TRIALS REGISTRATION: NCT00802464.

• Klíčová slova
• adjuvant, immunogenicity, recombinant subunit vaccine, safety, varicella-zoster virus,
• MeSH
• adjuvancia imunologická MeSH
• CD4-pozitivní T-lymfocyty imunologie   MeSH
• herpes zoster prevence a kontrola   MeSH
• lidé středního věku MeSH
• lidé MeSH
• počet CD4 lymfocytů MeSH
• proteiny virového obalu imunologie   MeSH
• protilátky virové imunologie   MeSH
• senioři MeSH
• subjednotkové vakcíny aplikace a dávkování   škodlivé účinky   imunologie   MeSH
• vakcína proti pásovému oparu aplikace a dávkování   škodlivé účinky   imunologie   MeSH
• virus varicella zoster imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• adjuvancia imunologická MeSH
• proteiny virového obalu MeSH
• protilátky virové MeSH
• subjednotkové vakcíny MeSH
• vakcína proti pásovému oparu MeSH

BACKGROUND: The herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01B 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 (CD42+) 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 CD42+ 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. CLINICAL TRIALS REGISTRATION: NCT01165177; NCT01165229.

• MeSH
• adjuvancia imunologická farmakologie   MeSH
• buněčná imunita imunologie   MeSH
• CD4-pozitivní T-lymfocyty MeSH
• herpes zoster imunologie   MeSH
• humorální imunita imunologie   MeSH
• imunogenicita vakcíny imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipid A analogy a deriváty   farmakologie   MeSH
• proteiny virového obalu imunologie   MeSH
• protilátky virové imunologie   MeSH
• saponiny farmakologie   MeSH
• senioři MeSH
• subjednotkové vakcíny imunologie   MeSH
• vakcína proti pásovému oparu imunologie   MeSH
• vakcinace metody   MeSH
• virus varicella zoster imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• adjuvancia imunologická MeSH
• AS01B adjuvant MeSH Prohlížeč
• glycoprotein E, varicella-zoster virus MeSH Prohlížeč
• lipid A MeSH
• proteiny virového obalu MeSH
• protilátky virové MeSH
• saponiny MeSH
• subjednotkové vakcíny MeSH
• vakcína proti pásovému oparu MeSH