Safety, immunogenicity, and lot-to-lot consistency of a quadrivalent inactivated influenza vaccine in children, adolescents, and adults: A randomized, controlled, phase III trial.

BACKGROUND: Inactivated quadrivalent influenza vaccine (IIV4) containing two influenza A strains and one strain from each B lineage (Yamagata and Victoria) may offer broader protection against seasonal influenza than inactivated trivalent influenza vaccine (IIV3), containing a single B strain. This study examined the safety, immunogenicity, and lot consistency of an IIV4 candidate. METHODS: This phase III, randomized, controlled, multicenter trial in children/adolescents (9 through 17 years) and adults (18 through 60 years) was conducted in Australia and in the Philippines in 2012. The study was double-blind for IIV4 lots and open-label for IIV4 vs IIV3. Children/adolescents were randomized 2:2:2:1 and adults 10:10:10:1 to receive one of three lots of IIV4 or licensed IIV3. Safety data were collected for up to 6 months post-vaccination. Hemagglutination inhibition and seroneutralization antibody titers were assessed pre-vaccination and 21 days post-vaccination. RESULTS: 1648 adults and 329 children/adolescents received IIV4, and 56 adults and 55 children/adolescents received IIV3. Solicited reactions, unsolicited adverse events, and serious adverse events were similar for IIV3 and IIV4 recipients in both age groups. Injection-site pain, headache, malaise, and myalgia were the most frequently reported solicited reactions, most of which were mild and resolved within 3 days. No vaccine-related serious adverse events or deaths were reported. Post-vaccination antibody responses, seroconversion rates, and seroprotection rates for the 3 strains common to both vaccines were comparable for IIV3 and IIV4 in both age groups. Antibody responses to IIV4 were equivalent among vaccine lots and comparable between age groups for each of the 4 strains. IIV4 met all European Medicines Agency immunogenicity criteria for adults for all 4 strains. CONCLUSIONS: In both age groups, IIV4 was well tolerated and caused no safety concerns, induced robust antibody responses to all 4 influenza strains, and met all EMA immunogenicity criteria for adults. CLINICAL TRIAL REGISTRY NUMBER: NCT01481454.

Acceptance of Intanza® 9 µg intradermal influenza vaccine in routine clinical practice in Australia and Argentina.

INTRODUCTION: Intanza® 9 µg (Sanofi Pasteur SA, Lyon, France), a split virion trivalent influenza vaccine delivered by intradermal injection with a microinjection system, became available as a vaccination for adults aged 18 to 59 years old, as of the 2010 southern hemisphere influenza season. METHODS: This study was designed to assess the acceptability of intradermal vaccination with Intanza 9 µg in routine clinical practice by adult vaccinees and their prescribers. Prescribers and healthy adults 18 to 59 years old in Australia and Argentina who had elected to be vaccinated with Intanza 9 µg during the 2010 southern hemisphere influenza season were recruited to complete surveys about their opinions of influenza vaccination and acceptance of the intradermal vaccination. RESULTS: 1402 vaccinees and 30 prescribers in Australia, and 264 vaccinees and 16 prescribers in Argentina responded to surveys. In both countries, 98% of vaccinees were satisfied or very satisfied with Intanza 9 µg. The main reasons for satisfaction were that the injection was considered minimally painful and that the vaccination was quickly administered. Most (95%) vaccinees reported that they would prefer to receive the same vaccination next year. Furthermore, 85% of prescribers were satisfied or very satisfied with the intradermal vaccine. CONCLUSION: Intradermal vaccination for seasonal influenza using Intanza 9 µg is well accepted both by adult vaccinees and prescribers. By providing an additional, well-accepted method, Intanza 9 µg might help increase seasonal influenza vaccination rates in adults.

The general practice experience of the swine flu epidemic in Victoria--lessons from the front line.

The swine influenza (H1N1 09) outbreak in Victoria has provided an excellent opportunity to review the Australian Health Management Plan for Pandemic Influenza (AHMPPI) and to assess its performance in practice. General practitioners play a major role in seasonal flu management, and it was expected that the AHMPPI would enable GPs on the front line to maintain this central role during the swine flu pandemic. The role of front-line GPs has been made extremely difficult by deficiencies in implementation of the AHMPPI, including resource supply failures, time-consuming administrative burdens, delays in receiving laboratory test results and approval for provision of oseltamivir to patients, and a lack of clear communication about policy changes as the situation progressed. We must use this experience to ensure timely and appropriate review of the AHMPPI and the way it is implemented. Better consultation with front-line clinicians, particularly GPs, is crucial and must occur as a matter of urgent priority.

Intradermal influenza vaccine administered using a new microinjection system produces superior immunogenicity in elderly adults: a randomized controlled trial.

BACKGROUND: Enhanced influenza vaccines are needed to provide improved protection for elderly individuals. The intradermal vaccination route was hypothesized to provide immunogenicity superior to that provided by the intramuscular vaccination route. METHODS: In a multicenter, randomized study, 1107 volunteers >60 years of age received intradermal trivalent inactivated influenza vaccine containing 15 or 21 microg of hemagglutinin per strain or intramuscular control vaccine. Intradermal vaccines used a novel microinjection system designed to ensure easy, convenient, consistent vaccination. The primary end points of the study were the strain-specific hemagglutination inhibition geometric mean titers (GMTs) noted 21 days after vaccination. Groups were compared using noninferiority and superiority analyses. RESULTS: For each strain, the GMTs noted in association with each intradermal vaccine were superior to those noted with the intramuscular control (adjusted P< .0001). Seroprotection rates, seroconversion rates, and mean titer increases were also superior for intradermally administered vaccine in all but one of the analyses undertaken. Systemic reactogenicity was comparable between routes. Local injection site reactions, particularly erythema but not pain, were more commonly associated with intradermal vaccination. CONCLUSIONS: For the first time, the intradermal vaccination route has been used to elicit immune responses significantly superior to those noted in association with the conventional intramuscular vaccination route. This was done using an easy-to-use, reliable microinjection system. This superior response is expected to enhance annual protection against influenza in this vulnerable population. TRIAL REGISTRATION: Clinicaltrials.gov registry number: NCT00296829.