Immunogenicity and safety of ZOSTAVAX(®) approaching expiry potency in individuals aged ≥50 years.

BACKGROUND: Age is a major risk factor for herpes zoster (HZ) and its potential long-term complication post-herpetic neuralgia (PHN). Due to the significant burden of HZ and PHN on patients' quality of life, it is vital that effective and well-tolerated vaccines are available to prevent HZ in older adults. ZOSTAVAX(®) vaccine was developed to prevent HZ and PHN in individuals ≥50 years (y) of age, and its clinical efficacy and safety have been demonstrated. AIMS AND METHODS: This phase 4, open-label, multicenter study was undertaken to assess the immunogenicity and safety of a single dose of ZOSTAVAX (refrigerator-stable formulation) given within 6 mo of its expiry date in individuals ≥50 y of age. The geometric mean fold rise (GMFR) from pre-vaccination to 4 weeks post-vaccination in varicella zoster virus (VZV) antibody titers was calculated. An acceptable antibody response was defined as a lower 95% confidence interval (CI) of GMFR > 1.4. Solicited and unsolicited injection-site reactions and systemic adverse events were recorded. RESULTS: The GMFR in VZV antibody titers was 3.1 (95% CI: 2.6, 3.8), satisfying the criterion for an acceptable VZV antibody response to ZOSTAVAX (minimum requirement: 1.4 GMFR). An acceptable rise in VZV antibody titers was observed in individuals of 50-59 y of age (GMFR 3.9; 95% CI: 2.9, 5.1) and in those ≥60 y of age (GMFR 2.5; 95% CI: 1.9, 3.2). ZOSTAVAX was well tolerated; no serious adverse events were reported. CONCLUSION: ZOSTAVAX elicits an acceptable immune response in immunocompetent individuals ≥50 y of age when stored as directed and administered during the 6 mo prior to expiration.

Evaluation of non-inferiority of intradermal versus adjuvanted seasonal influenza vaccine using two serological techniques: a randomised comparative study.

BACKGROUND: Although seasonal influenza vaccine is effective in the elderly, immune responses to vaccination are lower in the elderly than in younger adults. Strategies to optimise responses to vaccination in the elderly include using an adjuvanted vaccine or using an intradermal vaccination route. The immunogenicity of an intradermal seasonal influenza vaccine was compared with that of an adjuvanted vaccine in the elderly. METHODS: Elderly volunteers (age > or = 65 years) were randomised to receive a single dose of trivalent seasonal influenza vaccine: either a split-virion vaccine containing 15 microg haemagglutinin [HA]/strain/0.1-ml dose administered intradermally, or a subunit vaccine (15 microg HA/strain/0.5-ml dose) adjuvanted with MF59C.1 and administered intramuscularly. Blood samples were taken before and 21 +/- 3 days post-vaccination. Anti-HA antibody titres were assessed using haemagglutination inhibition (HI) and single radial haemolysis (SRH) methods. We aimed to show that the intradermal vaccine was non-inferior to the adjuvanted vaccine. RESULTS: A total of 795 participants were enrolled (intradermal vaccine n = 398; adjuvanted vaccine n = 397). Non-inferiority of the intradermal vaccine was demonstrated for the A/H1N1 and B strains, but not for the A/H3N2 strain (upper bound of the 95% CI = 1.53) using the HI method, and for all three strains by the SRH method. A post-hoc analysis of covariance to adjust for baseline antibody titres demonstrated the non-inferiority of the intradermal vaccine by HI and SRH methods for all three strains. Both vaccines were, in general, well tolerated; the incidence of injection-site reactions was higher for the intradermal (70.1%) than the adjuvanted vaccine (33.8%) but these reactions were mild and of short duration. CONCLUSIONS: The immunogenicity and safety of the intradermal seasonal influenza vaccine in the elderly was comparable with that of the adjuvanted vaccine. Intradermal vaccination to target the immune properties of the skin appears to be an appropriate strategy to address the challenge of declining immune responses in the elderly. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00554333.

Immunogenicity, large scale safety and lot consistency of an intradermal influenza vaccine in adults aged 18-60 years: Randomized, controlled, phase III trial.

BACKGROUND: Vaccination is the most effective way of reducing the large health and economic burden of influenza, yet vaccination coverage remains low, particularly among non-elderly adults. Intradermal influenza vaccine produce an effective immune response and represents an alternative to intramuscular influenza vaccination. RESULTS: The three industrial lots of intradermal vaccine were equivalent in terms of post-vaccination titres elicited by day 21. The intradermal and intramuscular vaccines induced similar post-vaccination titres, and satisfied all three immunogenicity criteria set out in the European regulatory guidelines for influenza vaccines for each of the three influenza strains. The solicited systemic reaction profile and the incidence and type of spontaneously reported adverse events were similar in the two vaccine groups and in line with the known safety profile of inactivated influenza vaccines. Injection site reactions were more frequent with intradermal vaccination. METHODS: A Phase III multicentre, randomised, controlled, double-blind (for the three different lots of intradermal vaccine) study assessed lot-to-lot consistency, immunogenicity and safety of an intradermal inactivated trivalent splitvirion influenza vaccine in 2,255 adults aged 18-60 years. Participants received one of three lots of intradermal vaccine containing 9 microg of haemagglutinin per influenza strain, or a licensed intramuscular control vaccine containing 15 microg haemagglutinin/strain. CONCLUSIONS: This intradermal vaccine containing 9 microg per influenza strain, provides an alternative to conventional intramuscular vaccination, has a reliable production method and is equally immunogenic and well tolerated in adults. The study was registered at clinicaltrials.gov (identifier NCT00383539).

Willingness to vaccinate or get vaccinated with an intradermal seasonal influenza vaccine: a survey of general practitioners and the general public in France and Germany.

INTRODUCTION: The elderly are at high risk of severe seasonal influenza and influenza-related death. Annual vaccination can effectively prevent influenza and its complications, and is recommended in the elderly. In the present study, surveys were undertaken in France and Germany to determine whether INTANZA (sanofi pasteur, Val-de-Reuil, France), the first intradermal influenza vaccine, administered using an innovative microneedle injection system, might influence physicians' likelihood of recommending influenza vaccination or the likelihood that the general public would seek influenza vaccination. METHODS: Physicians (France: n=260; Germany: n=223) and members of the general public aged ≥ 50 years (France: n=1706; Germany: n=1072) completed online surveys. Details of the INTANZA delivery system, and a "product profile" based on the properties of INTANZA, were presented. RESULTS: Most physicians and the general public found INTANZA and its microneedle injection system appealing. The main benefit of INTANZA, as perceived by physicians and the public, was the small needle size. Physicians also found the high immunogenicity compared with conventional intramuscular (IM) vaccines attractive. The majority of physicians believed that INTANZA would strongly help them to recommend vaccination to their unvaccinated patients (66% to 91%, depending upon patient characteristics); most (61% to 78%) would prefer to prescribe INTANZA rather than an IM vaccine. More than two-thirds of the unvaccinated general public would prefer INTANZA over IM vaccines, and the option of vaccination with INTANZA would encourage a large proportion of them to get vaccinated (60% to 74%), if it was recommended and they were given the choice. Physicians (≥ 82%) agreed that INTANZA may help increase vaccination coverage rates. CONCLUSION: The results of these surveys indicate that the availability of INTANZA may encourage physicians to recommend influenza vaccination, and members of the general public to get vaccinated. INTANZA may help to improve seasonal influenza vaccination coverage rates.

Intradermal influenza vaccine for older adults: a randomized controlled multicenter phase III study.

In a 3-year, randomized, controlled, open-label phase III trial enrolling 3707 adults aged > or = 60 years we evaluated whether the immunogenicity of an intradermal trivalent inactivated seasonal influenza vaccine, containing 15 microg of haemagglutinin per strain per 0.1 ml dose, is superior to that of a conventional intramuscular vaccine. Intradermal vaccine was given using an intradermal microinjection system. After the first vaccination, both vaccines satisfied the immunogenicity criteria for influenza vaccines for older adults set out in European regulatory guidelines, and geometric mean haemagglutination inhibition antibody titers and seroprotection rates were higher (statistically superior) with intradermal vaccination. Higher immune responses with intradermal vaccine were also observed after the 2nd and 3rd annual vaccinations. Both vaccines were well tolerated with similar systemic reactogenicity profiles. This intradermal influenza vaccine for older adults is a beneficial option for influenza protection, consistently enhancing antibody responses without compromising safety.