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Background This ongoing follow-up study evaluated the persistence of efficacy and immune responses for 6 additional years in adults vaccinated with the glycoprotein E (gE)-based adjuvanted recombinant zoster vaccine (RZV) at age ≥50 years in 2 pivotal efficacy trials (ZOE-50 and ZOE-70). The present interim analysis was performed after ≥2 additional years of follow-up (between 5.1 and 7.1 years [mean] post-vaccination) and includes partial data for year (Y) 8 post-vaccination. Methods Annual assessments were performed for efficacy against herpes zoster (HZ) from Y6 post-vaccination and for anti-gE antibody concentrations and gE-specific CD4[2+] T-cell (expressing ≥2 of 4 assessed activation markers) frequencies from Y5 post-vaccination. Results Of 7413 participants enrolled for the long-term efficacy assessment, 7277 (mean age at vaccination, 67.2 years), 813, and 108 were included in the cohorts evaluating efficacy, humoral immune responses, and cell-mediated immune responses, respectively. Efficacy of RZV against HZ through this interim analysis was 84.0% (95% confidence interval [CI], 75.9–89.8) from the start of this follow-up study and 90.9% (95% CI, 88.2–93.2) from vaccination in ZOE-50/70. Annual vaccine efficacy estimates were >84% for each year since vaccination and remained stable through this interim analysis. Anti-gE antibody geometric mean concentrations and median frequencies of gE-specific CD4[2+] T cells reached a plateau at approximately 6-fold above pre-vaccination levels. Conclusions Efficacy against HZ and immune responses to RZV remained high, suggesting that the clinical benefit of RZV in older adults is sustained for at least 7 years post-vaccination. Clinical Trials Registration. NCT02723773. [ABSTRACT FROM AUTHOR]

Background MMR II (M-M-R II [Merck & Co, Inc.]) is currently the only measles, mumps, and rubella (MMR) vaccine licensed in the United States. A second MMR vaccine would mitigate the potential risk of vaccine supply shortage or delay. In this study, we assessed the immunogenicity and safety of another MMR vaccine (MMR-RIT [Priorix, GlaxoSmithKline]) compared with those of the MMR II in 12- to 15-month-old children who received it as a first dose. Methods In this phase III, observer-blinded, noninferiority, lot-to-lot consistency clinical trial (ClinicalTrials.gov identifier NCT01702428), 5003 healthy children were randomly assigned to receive 1 dose of MMR-RIT (1 of 3 production lots) or MMR II along with other age-recommended routine vaccines. We evaluated the immunogenicity of all vaccines in terms of antibody concentrations (by using an enzyme-linked immunosorbent assay or electrochemiluminescence assay) and/or seroresponse rates 43 days after vaccination. We also assessed the reactogenicity and safety of the vaccines. Results Immunoresponses after vaccination with MMR-RIT were robust and noninferior to those after vaccination with the MMR II. Immunogenicity of the 3 production lots of MMR-RIT was consistent; more than 97% of the children had a seroresponse to MMR components. The coadministered vaccines elicited similar immunoresponses in the MMR-RIT and MMR II groups. Both MMR vaccines resulted in comparable reactogenicity profiles, and no safety concerns were detected. Conclusions If licensed, the MMR-RIT could provide a valid option for the prevention of measles, mumps, and rubella in children in the United States and would reduce potential risks of a vaccine shortage. [ABSTRACT FROM AUTHOR]

Background: One schedule for the capsular group B meningococcal vaccine 4CMenB is 2 doses that are administered 2 months apart for children aged 12-23 months, with a booster dose 12-24 months later. Our objective was to provide data on persistence of human serum bactericidal antibody (hSBA) titres in children up to 4 years of age after initial doses at 12-24 months, and immunogenicity of a booster dose at 48 months of age compared with vaccine-naive children.Methods: Children previously immunized, as part of a randomized controlled trial, with 2 doses of 4CMenB vaccine at 12-24 months of age received a booster at 4 years of age. Vaccine-naive age-matched toddlers received 2 doses of 4CMenB. Human serum bactericidal antibody titres against reference strains H44/76, 5/99, NZ98/254 and M10713 were evaluated before and after innoculation with 4CMenB vaccine in 4-year-old children.Results: Of 332 children in the study, 123 had previously received 4CMenB and 209 were vaccine-naive controls. Before the booster, the proportions of participants (previously vaccinated groups compared with controls) with hSBA titres of 1:5 or more were as follows: 9%-11% v. 1% (H44/76), 84%-100% v. 4% (5/99), 0%-18% v. 0% (NZ98/254) and 59%-60% v. 60% (M10713). After 1 dose of 4CMenB in previously immunized children, the proportions of participants achieving hSBA titres of 1:5 or more were 100% (H44/76 and 5/99), 70%-100% (NZ98/254) and 90%-100% (M10713).Interpretation: We found that waning of hSBA titres by 4 years of age occurred after 2 doses of 4CMenB vaccine administered at 12-24 months, and doses at 12-24 months have a priming effect on the immune system. A booster may be necessary to maintain hSBA titres of 1:5 or more among those children with increased disease risk. Trial registration: ClinicalTrials.gov, no. NCT01717638. [ABSTRACT FROM AUTHOR]

Summary Background This descriptive, non-comparative, phase III study evaluated the safety and tolerability of cell culture-derived (TIVc) and egg-derived (TIV) seasonal influenza vaccines in children at risk of influenza-related complications. Methods Four hundred and thirty subjects were randomized 2:1 to TIVc or TIV. Subjects aged 3 to <9 years received one dose (if previously vaccinated, n = 89) or two doses (if not previously vaccinated, n = 124) of the study vaccines; the 9 to <18-year-olds ( n = 213) received one dose. Reactogenicity was assessed for 7 days after vaccination; safety was monitored for 6 months. Results After any vaccination, the most frequently reported solicited local adverse event (AE) was tenderness/pain (TIVc 44%, 66%, 53% and TIV 56%, 51%, 65% in the age groups 3 to <6 years, 6 to <9 years, and 9 to <18 years, respectively) and the systemic AE was irritability (22% TIVc, 24% TIV) in 3 to <6-year-olds and headache in 6 to <9-year-olds (20% TIVc, 13% TIV) and 9 to <18-year-olds (21% TIVc, 26% TIV). There were no cases of severe fever (≥40 °C). No vaccine-related serious AEs were noted. New onset of chronic disease was reported in ≤1% of subjects. Conclusion TIVc and TIV had acceptable tolerability and similar safety profiles in at-risk children ( NCT01998477 ). [ABSTRACT FROM AUTHOR]

Zostavax ® is a live, attenuated varicella zoster virus (VZV) vaccine developed specifically for the prevention of HZ and PHN in individuals aged ≥50 years. During the clinical development of Zostavax, which was mainly in the US, the vaccine was administrated by the subcutaneous (SC) route. In Europe, many healthcare professionals prefer administering vaccines by the intramuscular (IM) route. This was an open-label, randomised trial conducted in 354 subjects aged ≥50 years. The primary objectives were to demonstrate that IM administration is both non-inferior to SC administration in terms of 4-week post-vaccination geometric mean titres (GMTs), and elicits an acceptable geometric mean fold-rise (GMFR) of antibody titres measured by glycoprotein enzyme-linked immunosorbent assay. Pre-specified non-inferiority was set as the lower bound of the 95% confidence interval (CI) of the GMT ratio (IM/SC) being >0.67. An acceptable GMFR for the IM route was pre-specified as the lower bound of its 95% CI being >1.4. Description of the VZV immune response using the interferon-gamma enzyme-linked immunospot (IFN-γ ELISPOT) assay and of the safety were secondary objectives. Participants were randomised to IM or SC administration (1:1). The baseline demographics were comparable between groups; mean age: 62.6 years (range: 50.0–90.5). The primary immunogenicity objectives were met (per protocol analysis): GMT ratio (IM/SC): 1.05 (95% CI: 0.93–1.18); GMFR: 2.7 (2.4–3.0). VZV immune response using IFN-γ ELISPOT were comparable between groups. Frequencies of systemic adverse events were comparable between groups. Injection-site reactions were less frequent with IM than SC route: erythema (15.9% versus 52.5%), pain (25.6% versus 39.5%) and swelling (13.6% versus 37.3%), respectively. In adults aged ≥50 years, IM administration of Zostavax elicited similar immune responses to SC administration and was well tolerated, with fewer injection-site reactions than with SC administration. [ABSTRACT FROM AUTHOR]

The article presents the study which determined the immunogenicity and reactogenecity of a multicomponent serogroup B Neisseria meningitidis (MenB) vaccine (4CMenB), as well as routine infant vaccines as given concomitantly or independently. The MenB vaccine is based on detergent-extracted outer membrane vesicles (OMV) with outer membrane proteins, including porin protein A. The randomized controlled study was conducted in several countries, namely, Belgium, Great Britain, Czech Republic, Germany, Italy and Spain.

BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV) antibody responses to the 9-valent human papillomavirus (9vHPV) vaccine among girls and boys (aged 9-14 years) receiving 2-dose regimens (months 0, 6 or 0,12) were noninferior to a 3-dose regimen (months 0, 2, 6) in young women (aged 16-26 years) 4 weeks after last vaccination in an international, randomized, open-label trial (NCT01984697). We assessed response durability through month 36. METHODS: Girls received 2 (months 0 and 6 [0, 6]: n = 301; months 0 and 12 [0,12]: n = 151) or 3 doses (months 0,2, and 6 [0, 2, 6]: n = 301); boys received 2 doses ([0, 6]: n = 301; [0, 12]: n = 150); and young women received 3 doses ([0, 2, 6]: n = 314) of 9vHPV vaccine. Anti-HPV geometric mean titers (GMTs) were assessed by competitive Luminex immunoassay (cLIA) and immunoglobulin G-Luminex immunoassay (IgG-LIA) through month 36. RESULTS: Anti-HPV GMTs were highest 1 month after the last 9vHPV vaccine regimen dose, decreased sharply during the subsequent 12 months, and then decreased more slowly. GMTs 2 to 2.5 years after the last regimen dose in girls and boys given 2 doses were generally similar to or greater than GMTs in young women given 3 doses. Across HPV types, most boys and girls who received 2 doses (cLIA: 81%-100%; IgG-LIA: 91%-100%) and young women who received 3 doses (cLIA: 78%-98%; IgG-LIA: 91%-100%) remained seropositive 2 to 2.5 years after the last regimen dose. CONCLUSIONS: Antibody responses persisted through 2 to 2.5 years after the last dose of a 2-dose 9vHPV vaccine regimen in girls and boys. In girls and boys, antibody responses generated by 2 doses administered 6 to 12 months apart may be sufficient to induce high-level protective efficacy through at least 2 years after the second dose. [ABSTRACT FROM AUTHOR]

Background 4CMenB is immunogenic in infants and toddlers. We assessed persistence of human complement serum bactericidal activity (hSBA) following a fourth dose administered at 12, 18 or 24 months and characterised the antibody response to a fifth dose administered at 4 years of age. Methods A phase 3, open label, multi-centre extension to a randomised controlled trial conducted in four countries (number of centres): Czech Republic (nineteen), Italy (four), Spain (four) and the United Kingdom (four). Four-year-old children who were either 4CMenB-naïve or had previously received a variety of 3-dose infant priming schedules and a booster vaccine as toddlers (follow-on group) were recruited. Venous blood samples were obtained to determine hSBA against four reference strains; acting as targets to assess immunity to each of the vaccine antigens, NadA (5/99), fHbp (H44/76), PorA (NZ98/254), and NHBA (M10713) at baseline (prior to vaccination, all participants) and one month following a dose of 4CMenB for all vaccine-naïve and follow-on participants primed with the 2, 3, 4 schedule, and a third of follow-on participants primed with a 2, 4, 6 month schedule. Results At baseline (prior to vaccination), the proportion of participants (n = 468) with hSBA titers ⩾ 5 was similar across all followon groups: 89–100% against 5/99; 12–35% for H44/76; 8–12% for NZ98/254 and 53–80% for M10713 compared with 5%, 0%, 0%; and 60% respectively, for the vaccine-naïve controls (n = 206). Following a dose of 4CMenB at 4 years of age, this increased to 100% (5/99), 97–100% (H44/76), 80–95 % (NZ98/254) and 84–100% (M10713) (n = 210), compared with 89%, 70%, 24%, and 76% respectively for vaccine-naïve controls (n = 192). Conclusion Waning of protective antibodies occurred 12–36 months after toddler booster regardless of age at boost. This was least marked against target strains 5/99 and M10713. A robust memory response occurred after a booster dose given at 4 years of age. [ABSTRACT FROM AUTHOR]

Background Neisseria meningitidis serogroup B (MnB) is a major cause of invasive meningococcal disease in infants. A conserved, surface-exposed lipoprotein, LP2086 (a factor H-binding protein [fHBP]), is a promising MnB vaccine target. A bivalent, recombinant vaccine targeting the fHBP (rLP2086) of MnB was developed. Methods This phase 1/2 clinical study was designed to assess the immunogenicity, safety, and tolerability of a 4-dose series of the rLP2086 vaccine at 20-, 60-, 120-, or 200-μg dose levels in vaccine-naive infants when given with routine childhood vaccines. The study was to consist of two phases: a single-blind sentinel phase and an open-label full enrollment phase. During the sentinel phase, randomization of subjects to the next higher dose was delayed pending a 14-day safety review of dose 1 of the preceding dose cohort. The full enrollment phase was to occur after completion of the sentinel phase. Results Local reactions were generally mild and adverse events infrequent; however, after only 46 infants were randomized into the study, fever rates were 64% and 90% in subjects receiving one 20- or 60-μg rLP2086 dose, respectively. Most fevers were <39.0 °C. Only 2 subjects in the 20-μg group and 1 subject in the 60-μg group experienced fevers >39.0 °C; no fevers were >40.0 °C. Due to these high fever rates, the study was terminated early. No immunogenicity data were collected. This report discusses the safety and acceptability of rLP2086 in infants after one 20- or 60-μg dose. Conclusion Due to the high fever rate experienced in the 20- and 60-μg groups, rLP2086 in the current formulation may not be acceptable for infants. [ABSTRACT FROM AUTHOR]