Varicella-zoster virus-specific antibody responses in 50-59-year-old recipients of zoster vaccine.

Prevaccination and 6-week postvaccination samples from the immunogenicity substudy (n = 2269) of the zoster vaccine (ZV) efficacy trial (N = 22 439) in 50-59-year-old subjects were examined for varicella-zoster virus-specific antibody responses to vaccination. The varicella-zoster virus geometric mean titer (GMT) and geometric mean fold rise were higher in ZV recipients than in placebo recipients (GMT, 660.0 vs 293.1 glycoprotein enzyme-linked immunosorbent assay units/mL [P < .001], respectively; geometric mean fold rise, 2.31 vs 1.00 [P < .025]). In each group there was a strong inverse correlation between postvaccination GMT and risk of subsequent herpes zoster. Although these data provide strong evidence that relates ZV-induced antibody and the risk of herpes zoster, a protective threshold was not determined. Clinical Trials Registration. NCT00534248.

Efficacy, safety, and tolerability of herpes zoster vaccine in persons aged 50-59 years.

BACKGROUND: Herpes zoster (HZ) adversely affects individuals aged 50-59, but vaccine efficacy has not been assessed in this population. This study was designed to determine the efficacy, safety, and tolerability of zoster vaccine for preventing HZ in persons aged 50-59 years. METHODS: This was a randomized, double-blind, placebo-controlled study of 22 439 subjects aged 50-59 years conducted in North America and Europe. Subjects were given 1 dose of licensed zoster vaccine (ZV) (Zostavax; Merck) and followed for occurrence of HZ for ≥1 year (mean, 1.3 years) postvaccination until accrual of ≥96 confirmed HZ cases (as determined by testing lesions swabs for varicella zoster virus DNA by polymerase chain reaction). Subjects were followed for all adverse events (AEs) from day 1 to day 42 postvaccination and for serious AEs (SAEs) through day 182 postvaccination. RESULTS: The ZV reduced the incidence of HZ (30 cases in vaccine group, 1.99/1000 person-years vs 99 cases in placebo group, 6.57/1000 person-years). Vaccine efficacy for preventing HZ was 69.8% (95% confidence interval, 54.1-80.6). AEs were reported by 72.8% of subjects in the ZV group and 41.5% in the placebo group, with the difference primarily due to higher rates of injection-site AEs and headache. The proportion of subjects reporting SAEs occurring within 42 days postvaccination (ZV, 0.6%; placebo, 0.5%) and 182 days postvaccination (ZV, 2.1%; placebo, 1.9%) was similar between groups. CONCLUSIONS: In subjects aged 50-59 years, the ZV significantly reduced the incidence of HZ and was well tolerated. CLINICAL TRIALS REGISTRATION: NCT00534248.

Evaluation of immunogenicity and safety of VARIVAX™ New Seed Process (NSP) in children.

Prior to availability of an effective vaccine, an estimated 4 million cases of varicella occurred annually in the United States, resulting in 10,000 hospitalizations and over 100 deaths. With the increased usage of a two-dose varicella vaccine (as recommended by the ACIP), approval of other VZV-containing products and the adoption of varicella vaccination in additional countries, the demand for VZV-containing vaccines has increased. This study (NCT02062502) evaluated the safety, tolerability, and immunogenicity of VARIVAX™ (VAR, varicella vaccine live) manufactured using a new seed manufacturing process (VARNSP) compared to the currently licensed VAR. Healthy children 12-23 months were randomized (1:1) into Group 1 (2 doses of VARNSP given concomitantly with M-M-R™ II, ∼3 months apart) versus  Group 2 (2 doses of VAR given concomitantly with M-M-R™ II, ∼3 months apart).  Serum samples collected prior to vaccination on Day 1 and 6 weeks Postdose 1 were tested for antibody to VZV using a glycoprotein enzyme-linked immunosorbent assay (gpELISA).  Safety was assessed Days 1 to 42 following each vaccination. Six weeks Postdose 1, the response rate (percent of subjects with VZV antibody titer ≥5 gpELISA units/mL) of VARNSP was non-inferior compared to VAR.  Vaccine-related adverse events (AEs) were comparable with the exception of measles-like rash, where a greater number of rashes were observed with VAR than VARNSP.  The 2 vaccination groups were comparable with incidence rates of AEs, injection-site AEs, vaccine-related AEs, systemic AEs, and serious AEs. This new process is an important innovation for the extreme demand of sustaining sufficient supplies of varicella vaccine to protect our communities against diseases caused by VZV.

Safety and tolerability of a high-potency zoster vaccine in adults >/= 50 or years of age.

BACKGROUND: Herpes zoster (HZ) incidence rises with age, especially after 50 years of age, probably due to waning varicella-zoster virus (VZV)-specific immunity. The Shingles Prevention Study [Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults, N Engl J Med 2005;352:2271-84], enrolled people >/= 60 or years of age and showed that zoster vaccine prevents HZ and postherpetic neuralgia (PHN), presumably through boosting VZV-specific immunity. This study of people >/= 50 or years of age compared the safety and tolerability of two zoster vaccine potencies. METHODS: Adults >/= 50 or years old enrolled in a randomized, double-blind, multicenter study to compare the safety and tolerability of one dose of two zoster vaccine potencies, approximately 58,000 and approximately 207,000 plaque-forming units/dose. Adverse experiences (AEs) were recorded on a standardized Vaccination Report Card for 42 days postvaccination. For assessment of injection-site AEs, clinically acceptable tolerability was predefined based on experience with PNEUMOVAX 23, a licensed vaccine recommended for use in older people. RESULTS: Six hundred and ninety-eight subjects (age 50-90 years, median 64 years) were enrolled. No serious vaccine-related AEs were reported. Similar AE rates were observed in the higher and lower potency groups (overall systemic AEs: 37.5 and 39.3%, vaccine-related systemic AEs: 10.9 and 13.2%, injection-site AEs: 63.0 and 59.8%). Rates for a combined endpoint of moderate or severe injection-site pain/tenderness/soreness and swelling were 17.2% (95% CI 13.9, 21.0) and 9.0% (95% CI 5.6, 13.4), respectively. Most combined endpoint events were reported as moderate in intensity. CONCLUSIONS: Both vaccine potencies were generally well tolerated in this study of people > or years of age. Although rates of some moderate or severe injection-site AEs were greater in the higher potency group, all rates met the prespecified criteria for clinically acceptable tolerability.