Karen J Ford

Immunogenicity of a tetravalent meningococcal glycoconjugate vaccine in infants: a randomized controlled trial.

CONTEXT Immunization with a meningococcal tetravalent (serogroup ACWY) glycoconjugate vaccine is recommended for all US adolescents. However, the currently licensed vaccine is poorly immunogenic in infancy, when the highest rates of disease are observed. OBJECTIVE To determine the immunogenicity of a novel tetravalent CRM(197)-conjugated meningococcal vaccine (MenACWY) in infants. DESIGN, SETTING, AND PARTICIPANTS Randomized, open-label, controlled study of 225 UK and 196 Canadian 2-month-olds from August 2004 to September 2006. INTERVENTION UK infants received a primary course of MenACWY (at 2, 3, and 4 months or 2 and 4 months) or Neisseria meningitidis serogroup C monovalent meningococcal glycoconjugate vaccine (MenC) (at 2 and 4 months). All received MenACWY at 12 months. Canadian infants received MenACWY at 2, 4, and 6 months or 2 and 4 months; at 12 months they received MenACWY, a plain tetravalent polysaccharide vaccine, or no vaccine. MAIN OUTCOME MEASURE Percentage of infants with a human complement serum bactericidal activity (hSBA) titer >or=1:4 after a primary course of MenACWY and after a 12-month booster. Safety and reactogenicity of MenACWY were also assessed. RESULTS According to the prespecified per-protocol analysis, the percentages (95% CIs) of MenACWY 2-, 3-, and 4-month recipients with hSBA titers >or=1:4 after primary immunization were serogroup A, 93% (84%-98%); C, 96% (89%-99%); W-135, 97% (90%-100%); and Y, 94% (86%-98%). With a post hoc intention-to-treat analysis with imputed values for missing data, these values were unchanged for serogroups C and Y; for serogroup A, values were 92% (84%-97%), and for W-135, 97% (91%-99%). For the per-protocol analysis of MenACWY 2-, 4-, and 6-month recipients, the percentages (95% CIs) of responders were A, 81% (71%-89%); C, 98% (92%-100%); W-135, 99% (93%-100%); and Y, 98% (92%-100%). With the imputed value analysis, these values were A, 83% (74%-89%); C, 98% (93%-99%); W-135, 99% (94%-100%); and Y, 98% (92%-99%). At least 84% of MenACWY 2- and 4-month recipients achieved hSBA titers >or=1:4 for serogroups C, W-135, and Y after primary immunization, as did at least 60% for serogroup A (per-protocol and imputation analysis). At least 95% of primary and booster MenACWY recipients achieved hSBA titers >or=1:4 for serogroups C, W-135, and Y at 13 months, as did at least 84% for serogroup A (per-protocol and imputation analysis). During the primary immunization course, postimmunization pain on leg movement was observed in 2% of UK MenACWY 2- and 4-month recipients and 4% of MenC 2- and 4-month recipients; a temperature of 38 degrees C or greater was observed in 4% and 2% in these groups, respectively. CONCLUSION MenACWY is well tolerated and immunogenic in infancy. Trial Registration clinicaltrials.gov Identifier: NCT00262002.

Immunogenicity and immune memory of a nonadjuvanted quadrivalent meningococcal glycoconjugate vaccine in infants.

Background: The highest rate of invasive meningococcal disease is among children under 2 years of age. There is currently no licensed quadrivalent (serogroups A, C, W-135, and Y) meningococcal glycoconjugate vaccine approved for infants. We evaluated the immunogenicity and reactogenicity of a novel quadrivalent nonadjuvanted meningococcal glycoconjugate vaccine (MenACWY-CRM) in healthy infants. Methods: One hundred eighty infants (90 in Canada and 90 in the United Kingdom) received 2 doses of MenACWY-CRM at 2 and 4 months of age administered concomitantly with routine infant vaccines. At 12 months of age, the Canadian infants received either MenACWY-CRM or a reduced dose of a licensed meningococcal polysaccharide vaccine. In the United Kingdom, all infants received a further dose of MenACWY-CRM. The serological marker of protection was a titer of ≥1:4 using a serum bactericidal assay with human complement (hSBA). Results: Two doses of MenACWY-CRM induced hSBA titers ≥1:4 in 57% (95% confidence interval [CI]: 45–67) and 50% (95% CI: 38–62) of infants against serogroup A in Canada and the United Kingdom, respectively, 93% (95% CI: 85–97) and 86% (95% CI: 46–93) against serogroup C, 95% (95% CI: 87–99) and 82% (95% CI: 71–90) against serogroup W-135, and 91% (95% CI: 82–96) and 74% (95% CI: 63–83) against serogroup Y. After a booster dose of MenACWY-CRM at 12 months, at least 94% of participants achieved hSBA titers ≥1:4 against each of the serogroups C, W-135, and Y and more than 79% against serogroup A. The vaccine was well tolerated. Conclusions: The nonadjuvanted MenACWY-CRM is immunogenic and well tolerated in infancy and could provide broad protection against meningococcal disease in this vulnerable age group.

Seroprevalence and placental transmission of maternal antibodies specific for Neisseria meningitidis Serogroups A, C, Y and W135 and influence of maternal antibodies on the immune response to a primary course of MenACWY-CRM vaccine in the United Kingdom.

Background: Maternal antibodies give neonates some protection against bacterial infection. We measured antibodies against Neisseria meningitidis serogroups A, C, Y and W135 in mothers and their 2-month-old infants at study enrollment. We also assessed the impact of maternal antibody present at 2 months of age on the immune response to a primary course of quadrivalent meningococcal conjugate vaccine (MenACWY-CRM197) given at 2 and 4 months of age. Methods: This was a single-center, open-label, randomized study undertaken in Oxford, United Kingdom. Two hundred sixteen healthy infants were enrolled in the study and vaccinated with MenACWY-CRM197 at 2 and 4 months of age. Blood was obtained from all mothers, in a subset of infants at 2 months and all infants at 5 months. Antibody and memory B-cell responses at 5 months were correlated with maternal antibodies. Results: Mothers had low IgG antibodies against serogroups C, W135 and Y polysaccharides, but high serogroup A antibody, whereas 61–78% had protective human complement serum bactericidal activity (hSBA) (≥1:4) for serogroups C, W135 and Y but only 31% for serogroup A. Only 9%, 32%, 45% and 19% of 2-month-old infants had hSBA ≥1:4 for serogroups A, C, W135 and Y, respectively. Maternal antibody had little association on responses to MenACWY-CRM197, except a moderate negative association between MenC-specific bactericidal antibody at 2 and 5 months (r = −0.5, P = 0.006, n = 28) and between carrier-specific IgG antibody at 2 months and MenC-specific hSBA/IgG antibody at 5 months (r = −0.4, P = 0.02 and 0.04, n = 32 and 23). Nonetheless, 90% of infants achieved protective MenC-hSBA titers after vaccination at 2 and 4 months of age. Conclusions: The levels of serogroup-specific meningococcal antibodies were low in mothers and 2-month-old infants. Immunizing mothers before or during pregnancy with meningococcal conjugate vaccines might increase antibody levels in early infancy and provide protection against infection due to N. meningitidis.

Self-reported adverse events in adolescents aged 13-18 years after mass vaccination with pertussis-containing vaccine, following a school outbreak

L.J. McCann *, K.J. Ford , A.J. Pollard , R. Kulkarni , G. Amirthalingam , A. Smith , N.D. McCarthy a Thames Valley Public Health England Centre, Public Health England, Chilton, UK b Field Epidemiology Training Programme, Public Health England, UK European Programme for Intervention Epidemiology Training, European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK NHS Berkshire, UK f Immunisation, Hepatitis and Blood Safety Department, Public Health England, London, UK

Neuraminidase inhibitors produce a small reduction in duration of seasonal flu in children and reduce transmission in affected households, but effects on serious complications are unclear

Commentary on: Shun-ShinMThompsonMHeneghanC. Neuraminidase inhibitors for treatment and prophylaxis of influenza in children: systematic review and meta-analysis of randomised controlled trials. BMJ 2009;339:b3172.