lipid-a and Herpes-Zoster

Shingrix

Topics: Activities of Daily Living; Aged; Herpes Zoster; Herpes Zoster Vaccine; Herpesvirus 3, Human; Humans; Immunocompromised Host; Lipid A; Middle Aged; Neuralgia, Postherpetic; Saponins; Vaccines, Subunit; Viral Envelope Proteins

Topics: Adjuvants, Immunologic; Aged; Aged, 80 and over; Herpes Zoster; Herpes Zoster Vaccine; Herpesvirus 3, Human; Humans; Immunization Schedule; Immunogenicity, Vaccine; Injections, Intramuscular; Lipid A; Middle Aged; Saponins; Time Factors; Treatment Outcome; Vaccination; Vaccines, Subunit; Viral Envelope Proteins

In this Phase III, open-label trial conducted in the US and Estonia, 354 adults ≥50 years were randomized 1:1:1 to receive 2 HZ/su doses 2, 6, or 12 months apart. gE-specific humoral immune responses were evaluated at pre-vaccination, 1 and 12 months post-dose 2. Co-primary objectives were to compare immune responses to HZ/su 1 month post-dose 2 when given 6-months or 12-months apart to those administered 2-months apart. For each participant, safety information was collected from dose 1 to 12 months post-dose 2.. 346 participants completed the study and 343 were included in the according-to-protocol cohort for immunogenicity. One month post-dose 2, vaccine response rates were 96.5% (97.5% confidence interval [CI]: 90.4; 99.2) and 94.5% (97.5% CI: 87.6; 98.3) for the 0, 6- and 0, 12-month schedules, respectively, both schedules meeting the pre-defined criterion. Non-inferiority of anti-gE geometric mean concentrations was demonstrated for HZ/su administered on 0, 6-month compared to a 0, 2-month schedule; however, HZ/su administered on a 0, 12-month schedule did not meet the non-inferiority criterion. Injection site pain was the most commonly reported solicited adverse event (AE). 26 participants each reported at least 1 serious AE; none were assessed as related to vaccination.. Immune responses to HZ/su administered at 0, 6-month were non-inferior to those elicited by a 0, 2-month schedule. HZ/su exhibited a clinically acceptable safety profile for all dosing intervals.. Clinicaltrials.gov (NCT01751165).

Topics: Aged; Antibodies, Viral; Estonia; Female; Herpes Zoster; Herpes Zoster Vaccine; Herpesvirus 3, Human; Humans; Immunization Schedule; Immunogenicity, Vaccine; Lipid A; Male; Middle Aged; Saponins; United States; Vaccination; Vaccines, Subunit; Viral Envelope Proteins

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.. 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.. 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.. Most HZ/su recipients developed robust immune responses persisting for 3 years following vaccination.. NCT01165177; NCT01165229.

Topics: Adjuvants, Immunologic; Aged; Antibodies, Viral; CD4-Positive T-Lymphocytes; Female; Herpes Zoster; Herpes Zoster Vaccine; Herpesvirus 3, Human; Humans; Immunity, Cellular; Immunity, Humoral; Immunogenicity, Vaccine; Lipid A; Male; Middle Aged; Saponins; Vaccination; Vaccines, Subunit; Viral Envelope Proteins

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.. 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.. 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.. 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.

Topics: Aged; Aged, 80 and over; Antibodies, Viral; CD4-Positive T-Lymphocytes; Drug Combinations; Female; Follow-Up Studies; Herpes Zoster; Herpes Zoster Vaccine; Humans; Immunity, Cellular; Immunity, Humoral; Lipid A; Male; Middle Aged; Saponins; Vaccines, Subunit; Viral Envelope Proteins

Topics: Adult; Allergy and Immunology; Costs and Cost Analysis; Female; Herpes Zoster; Herpes Zoster Vaccine; Herpesvirus 3, Human; Humans; Hypersensitivity; Insurance, Health, Reimbursement; Lipid A; Male; Mass Vaccination; Middle Aged; Practice Guidelines as Topic; Saponins; United States; Vaccines, Synthetic; Viral Envelope Proteins