Safety and Immunogenicity of DTaP5-IPV Compared With DTaP5 Plus IPV as the Fifth Dose in Children 4-6 Years of Age.

BACKGROUND: Immunogenicity and safety of stand-alone diphtheria, tetanus toxoid, 5-component acellular pertussis vaccine adsorbed, inactivated poliovirus (IPV) combination vaccine (DTaP5-IPV) was compared with separate DTaP5 plus IPV vaccines as fifth dose in children 4-6 years of age. METHODS: In this phase III, controlled, multicenter, randomized, open-label study, participants were randomized to DTaP5-IPV plus measles/mumps/rubella (MMR) and varicella virus (VZV) vaccines (group 1; N = 324), DTaP5+IPV with MMR and VZV (group 2; N = 327), DTaP5-IPV with/without MMR/VZV (group 3; N = 2419) or DTaP5+IPV with/without MMR/VZV (group 4; N = 302). Immunogenicity endpoints (groups 1 and 2) included booster response rates and antibody geometric mean concentrations (GMCs). Noninferiority of DTaP5-IPV to DTaP5+IPV was evaluated based on differences (groups 1 and 2) in booster rates and postvaccination GMC ratios. Safety endpoints (all groups) included all adverse events. RESULTS: Noninferiority of DTaP5-IPV compared with DTaP5+IPV for all antigens was achieved. Booster rate differences were 5.4% for pertussis toxoid (PT); 7.4% for filamentous hemagglutinin; 3.7% for pertactin (PRN); 4.8% for fimbriae types 2 and 3; -0.1% for tetanus; -1.9% for diphtheria; 3.7% for poliovirus 1; -0.7% for poliovirus 2 and 0.3% for poliovirus 3. GMC ratios were 1.97 for PT; 1.56 for filamentous hemagglutinin; 1.51 for PRN; 1.33 for fimbriae types 2 and 3; 1.17 for tetanus; 1.20 for diphtheria; 1.27 for poliovirus 1; 0.90 for poliovirus 2 and 1.34 for poliovirus 3. Rates of immediate and unsolicited adverse events, solicited injection site reactions and systemic reactions were similar between groups. CONCLUSIONS: DTaP5-IPV was safe and immunogenic in children 4-6 years of age.

Safety and immunogenicity of a quadrivalent intradermal influenza vaccine in adults.

BACKGROUND: An intradermal (ID) trivalent split-virion influenza vaccine (IIV3-ID) (Fluzone(®) Intradermal, Sanofi Pasteur, Swiftwater, PA) has been available in the US since the 2011/2012 influenza season for adults aged 18-64 years. This study examined whether adding a second B-lineage strain affects immunogenicity and safety. METHODS: This randomized, double-blind, multicentre trial evaluated the immunogenicity and safety of an intradermal quadrivalent split-virion influenza vaccine (IIV4-ID) in adults 18-64 years of age in the US during the 2012-2013 influenza season. Participants were randomized 2:1:1 to receive a single injection of IIV4-ID, licensed IIV3-ID, or an investigational IIV3-ID containing the alternate B-lineage strain. Haemagglutination inhibition antibody titres were assessed in two-thirds of participants before vaccination and 28 days after vaccination. RESULTS: 1672 participants were vaccinated with IIV4-ID, 837 with licensed IIV3-ID, and 846 with an investigational IIV3-ID. For all four vaccine strains, antibody responses to IIV4-ID were statistically non-inferior to the response to the IIV3-ID vaccines containing the matched strains. For both B strains, post-vaccination antibody responses to IIV4-ID were statistically superior to the responses to IIV3-ID lacking the corresponding B strain. Adverse events were similar for IIV4-ID and IIV3-ID. The most commonly reported solicited reactions were pain, pruritus, myalgia, headache, and malaise; and most were grade 1 or 2 and appeared and resolved within 3 days of vaccination. IIV4-ID was statistically non-inferior to the two pooled IIV3-ID vaccines for the proportions of participants with at least one grade 2 or 3 systemic reaction. CONCLUSIONS: Antibody responses to the IIV4-ID were non-inferior to IIV3-ID for the A and matched B strains and superior for the unmatched B strains. IIV4-ID was well tolerated without any safety concerns. IIV4-ID may help address an unmet need due to mismatched B strains in previous influenza vaccines.

Safety and immunogenicity of revaccination with reduced dose intradermal and standard dose intramuscular influenza vaccines in adults 18-64 years of age.

BACKGROUND: This clinical trial examined the safety and immunogenicity of annual revaccination with Fluzone(®) Intradermal (Sanofi Pasteur, Swiftwater, PA) vaccine compared to a standard intramuscular (IM) split-virion trivalent influenza vaccine (Fluzone(®), Sanofi Pasteur). METHODS: This phase II, active-controlled, multi-centre, open-label trial was conducted in 2009 and 2010, and enrolled 1250 adults 18-64 years of age who were randomly selected from participants in a phase III influenza vaccine trial the previous year (NCT00772109). Subjects who had previously received the ID vaccine were randomized 2:1 to be revaccinated with the ID or IM vaccine and those who previously received the IM vaccine were randomized 1:1. Solicited reactions were recorded on the day of vaccination and continuing for the next 7 days, non-serious adverse events for 28 days, and serious adverse events for 6 months after vaccination. Hemagglutination inhibition antibody titres were assessed pre-vaccination and at day 28. RESULTS: Reactions were well-tolerated and resolved in the first 7 days, but erythema, induration, swelling, pruritus and ecchymosis were reported by more subjects receiving the ID vaccine than the IM vaccine. Compared to receipt of IM vaccine in the previous year, ID vaccine in the previous year led to statistically higher rates of erythema, swelling and induration after IM vaccine in the second year. Injection-site pain and systemic reactions did not differ between ID and IM vaccines. No treatment-related serious adverse events were reported. Geometric mean antibody titres, seroprotection rates, and seroconversion rates were non-inferior for the ID and IM vaccines for all three viral strains. CONCLUSIONS: The ID vaccine was as immunogenic as the IM vaccine, and raised no safety concerns. It can be used interchangeably with the IM vaccine for annual revaccination in adults 18-64 years of age in consecutive years without safety concerns.

Intradermally-administered influenza virus vaccine is safe and immunogenic in healthy adults 18-64 years of age.

BACKGROUND: To increase vaccine acceptance, intradermal (ID) influenza vaccine (Fluzone(®) Intradermal, Sanofi Pasteur Inc.) may be an attractive alternative to intramuscular (IM) vaccination due to smaller needle and volume injected. METHODS: A multicenter, randomized (2:1 ID vs IM vaccines) study, blinded for ID vaccine lots, was conducted among 4292 adults 18-64 years of age enrolled in October 2008. Three lots of investigational trivalent influenza vaccine containing 9µg hemagglutinin (HA) per strain in 0.1mL administered ID with a 30 gauge, 1.5mm long needle were compared to standard dose vaccine (0.5mL containing 15µg HA/strain) given IM. RESULTS: The post-vaccination antibody geometric mean titers (GMT) for the ID vaccine were similar to the IM vaccine (H1N1: 193.2 vs. 178.3, H3N2: 246.7 vs. 230.7, and B: 102.5 vs. 126.9). Non-inferiority was met for the ID vaccine compared to IM vaccine as assessed by antibody GMT ratios (IM/ID) for all three virus strains (H1N1: 0.92, H3N2: 0.94, and B: 1.24). Seroconversion rates were non-inferior for H1N1 and H3N2, but not for B (ID vs. IM: H1N1: 61.2% vs. 60.5%, H3N2: 75.3% vs. 74.8%, and B: 46.2% vs. 54.2%). Seroprotection (HAI titer ≥1:40) rates were similar between groups (ID vs. IM, H1N1: 91.1% vs. 91.7%, H3N2: 90.7% vs. 91.4%, and B: 87.4% vs. 89.3%). Local injection site reactions overall were more common with ID than IM vaccine (ID vs. IM: 89.2% vs. 60.2%), but were usually grade 1 or 2 and transient. The frequencies of local injection site pain and systemic reactions were similar between vaccine groups, except more myalgia with IM vaccine. CONCLUSIONS: The ID vaccine elicited immune responses comparable to IM vaccine except for the seroconversion rate to B virus. With the exception of pain, local injection site reactions were more common with the ID vaccine, but well-tolerated and of short duration. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00772109.

Adhesion of single bacterial cells in the micronewton range.

The adhesion of bacteria to surfaces plays critical roles in the environment, disease, and industry. In aquatic environments, Caulobacter crescentus is one of the first colonizers of submerged surfaces. Using a micromanipulation technique, we measured the adhesion force of single C. crescentus cells attached to borosilicate substrates through their adhesive holdfast. The detachment forces measured for 14 cells ranged over 0.11 to 2.26 microN, averaging 0.59 +/- 0.62 microN. Based on the calculation of stress distribution with the finite element analysis method (dividing an object into small grids and calculating relevant parameters for all of the elements), the adhesion strength between the holdfast and the substrate is >68 N/mm(2) in the central region of contact. To our knowledge, this strength of adhesion is the strongest ever measured for biological adhesives.