BACKGROUND: The adjuvanted recombinant zoster vaccine (RZV) is highly immunogenic and efficacious in adults ≥50 years of age. We evaluated (1) long-term immunogenicity of an initial 2-dose RZV schedule, by following up adults vaccinated at ≥60 years of age and by modeling, and (2) immunogenicity of 2 additional doses administered 10 years after initial vaccination. METHODS: Persistence of humoral and cell-mediated immune (CMI) responses to 2 initial RZV doses was assessed through 10 years after initial vaccination, and modeled through 20 years using a Piecewise, Power law and Fraser model. The immunogenicity and safety of 2 additional RZV doses were also evaluated. RESULTS: Seventy adults were enrolled. Ten years after initial vaccination, humoral and CMI responses were approximately 6-fold and 3.5-fold, respectively, above those before the initial vaccination levels. Predicted immune persistence through 20 years after initial vaccination was similar across the 3 models. Sixty-two participants (mean age [standard deviation], 82.6 [4.4] years) received ≥1 additional RZV dose. Strong anamnestic humoral and CMI responses were elicited by 1 additional dose, without further increases after a second additional dose. CONCLUSIONS: Immune responses to an initial 2-dose RZV course persisted for many years in older adults. Strong anamnestic immune responses can be induced by additional dosing 10 years after the initial 2-dose course. CLINICAL TRIALS REGISTRATION: NCT02735915.

• Keywords
• adjuvanted recombinant zoster vaccine, herpes zoster, persistence of immune response, safety,
• MeSH
• Adjuvants, Immunologic administration & dosage   adverse effects   MeSH
• Herpes Zoster prevention & control   MeSH
• Immunogenicity, Vaccine * MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Vaccines, Synthetic administration & dosage   adverse effects   immunology   MeSH
• Herpes Zoster Vaccine administration & dosage   adverse effects   MeSH
• Vaccination MeSH
• Herpesvirus 3, Human immunology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adjuvants, Immunologic MeSH
• Vaccines, Synthetic MeSH
• Herpes Zoster Vaccine MeSH

IMPORTANCE: Herpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster. OBJECTIVE: To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients. DESIGN, SETTING, AND PARTICIPANTS: Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT. INTERVENTIONS: Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n = 922) or placebo (n = 924) administered into the deltoid muscle; the first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter. MAIN OUTCOMES AND MEASURES: The primary end point was occurrence of confirmed herpes zoster cases. RESULTS: Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [37%] women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study. During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P < .001), equivalent to 68.2% vaccine efficacy. Of 8 secondary end points, 3 showed significant reductions in incidence of postherpetic neuralgia (vaccine, n=1; placebo, n=9; IRR, 0.1; 95% CI, 0.00-0.78; P = .02) and of other prespecified herpes zoster-related complications (vaccine, n=3; placebo, n=13; IRR, 0.22; 95% CI, 0.04-0.81; P = .02) and in duration of severe worst herpes zoster-associated pain (vaccine, 892.0 days; placebo, 6275.0 days; hazard ratio, 0.62; 95% CI, 0.42-0.89; P = .01). Five secondary objectives were descriptive. Injection site reactions were recorded in 86% of vaccine and 10% of placebo recipients, of which pain was the most common, occurring in 84% of vaccine recipients (grade 3: 11%). Unsolicited and serious adverse events, potentially immune-mediated diseases, and underlying disease relapses were similar between groups at all time points. CONCLUSIONS AND RELEVANCE: Among adults who had undergone autologous HSCT, a 2-dose course of recombinant zoster vaccine compared with placebo significantly reduced the incidence of herpes zoster over a median follow-up of 21 months. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01610414.

• MeSH
• Adjuvants, Immunologic MeSH
• Transplantation, Autologous MeSH
• Adult MeSH
• Herpes Zoster epidemiology   prevention & control   MeSH
• Hospitalization statistics & numerical data   MeSH
• Immunocompromised Host * MeSH
• Incidence MeSH
• Injections, Intramuscular MeSH
• Single-Blind Method MeSH
• Middle Aged MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Neuralgia, Postherpetic prevention & control   MeSH
• Proportional Hazards Models MeSH
• Vaccines, Synthetic administration & dosage   MeSH
• Hematopoietic Stem Cell Transplantation * MeSH
• Herpes Zoster Vaccine * administration & dosage   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH
• Names of Substances
• Adjuvants, Immunologic MeSH
• Vaccines, Synthetic MeSH
• Herpes Zoster Vaccine * 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.

• Keywords
• herpes zoster, herpes zoster (shingles) vaccine, immunity, persistence, prediction modeling, prevention, subunit gE vaccine, varicella-zoster virus,
• MeSH
• Time Factors MeSH
• Cytokines analysis   MeSH
• Adult MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Lipid A administration & dosage   analogs & derivatives   MeSH
• Follow-Up Studies MeSH
• Antibodies, Viral blood   MeSH
• Saponins administration & dosage   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Vaccines, Subunit administration & dosage   immunology   MeSH
• T-Lymphocytes immunology   MeSH
• Herpes Zoster Vaccine administration & dosage   immunology   MeSH
• Herpesvirus 3, Human immunology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase II MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• AS01B adjuvant MeSH Browser
• Cytokines MeSH
• Lipid A MeSH
• Antibodies, Viral MeSH
• Saponins MeSH
• Vaccines, Subunit MeSH
• Herpes Zoster Vaccine 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
• Adjuvants, Immunologic pharmacology   MeSH
• Immunity, Cellular immunology   MeSH
• CD4-Positive T-Lymphocytes MeSH
• Herpes Zoster immunology   MeSH
• Immunity, Humoral immunology   MeSH
• Immunogenicity, Vaccine immunology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lipid A analogs & derivatives   pharmacology   MeSH
• Viral Envelope Proteins immunology   MeSH
• Antibodies, Viral immunology   MeSH
• Saponins pharmacology   MeSH
• Aged MeSH
• Vaccines, Subunit immunology   MeSH
• Herpes Zoster Vaccine immunology   MeSH
• Vaccination methods   MeSH
• Herpesvirus 3, Human immunology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Adjuvants, Immunologic MeSH
• AS01B adjuvant MeSH Browser
• glycoprotein E, varicella-zoster virus MeSH Browser
• Lipid A MeSH
• Viral Envelope Proteins MeSH
• Antibodies, Viral MeSH
• Saponins MeSH
• Vaccines, Subunit MeSH
• Herpes Zoster Vaccine MeSH