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      H1N1 Antibody Persistence 1 Year After Immunization With an Adjuvanted or Whole-Virion Pandemic Vaccine and Immunogenicity and Reactogenicity of Subsequent Seasonal Influenza Vaccine: A Multicenter Follow-on Study

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          Abstract

          Two doses of AS03 B-adjuvanted pandemic influenza vaccine may be sufficient to maintain seroprotection across 2 influenza seasons. Administration of trivalent influenza vaccine to children who previously received 2 doses of pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain.

          Abstract

          Background.  We investigated antibody persistence in children 1 year after 2 doses of either an AS03 B-adjuvanted split-virion or nonadjuvanted whole-virion monovalent pandemic influenza vaccine and assessed the immunogenicity and reactogenicity of a subsequent dose of trivalent influenza vaccine (TIV).

          Methods.  Children previously immunized at age 6 months to 12 years in the original study were invited to participate. After a blood sample was obtained to assess persistence of antibody against swine influenza A/H1N1(2009) pandemic influenza, children received 1 dose of 2010/2011 TIV, reactogenicity data were collected for 7 days, and another blood sample was obtained 21 days after vaccination.

          Results.  Of 323 children recruited, 302 received TIV. Antibody persistence (defined as microneutralization [MN] titer ≥1:40) 1 year after initial vaccination was significantly higher in the AS03 B-adjuvanted compared with the whole-virion vaccine group, 100% (95% confidence interval [CI], 94.1%–100%) vs 32.4% (95% CI, 21.5%–44.8%) in children immunized <3 years old and 96.9% (95% CI, 91.3%–99.4%) vs 65.9% (95% CI, 55.3%–75.5%) in those 3–12 years old at immunization, respectively ( P < .001 for both groups). All children receiving TIV had post-vaccination MN titers ≥1:40. Although TIV was well tolerated in all groups, reactogenicity in children <5 years old was slightly greater in those who originally received AS03 B-adjuvanted vaccine.

          Conclusions.  This study provides serological evidence that 2 doses of AS03 B-adjuvanted pandemic influenza vaccine may be sufficient to maintain protection across 2 influenza seasons. Administration of TIV to children who previously received 2 doses of either pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain.

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          Detection of antibody to avian influenza A (H5N1) virus in human serum by using a combination of serologic assays.

          From May to December 1997, 18 cases of mild to severe respiratory illness caused by avian influenza A (H5N1) viruses were identified in Hong Kong. The emergence of an avian virus in the human population prompted an epidemiological investigation to determine the extent of human-to-human transmission of the virus and risk factors associated with infection. The hemagglutination inhibition (HI) assay, the standard method for serologic detection of influenza virus infection in humans, has been shown to be less sensitive for the detection of antibodies induced by avian influenza viruses. Therefore, we developed a more sensitive microneutralization assay to detect antibodies to avian influenza in humans. Direct comparison of an HI assay and the microneutralization assay demonstrated that the latter was substantially more sensitive in detecting human antibodies to H5N1 virus in infected individuals. An H5-specific indirect enzyme-linked immunosorbent assay (ELISA) was also established to test children's sera. The sensitivity and specificity of the microneutralization assay were compared with those of an H5-specific indirect ELISA. When combined with a confirmatory H5-specific Western blot test, the specificities of both assays were improved. Maximum sensitivity (80%) and specificity (96%) for the detection of anti-H5 antibody in adults aged 18 to 59 years were achieved by using the microneutralization assay combined with Western blotting. Maximum sensitivity (100%) and specificity (100%) in detecting anti-H5 antibody in sera obtained from children less than 15 years of age were achieved by using ELISA combined with Western blotting. This new test algorithm is being used for the seroepidemiologic investigations of the avian H5N1 influenza outbreak.
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            Paediatric mortality related to pandemic influenza A H1N1 infection in England: an observational population-based study.

            Young people (aged 0-18 years) have been disproportionately affected by pandemic influenza A H1N1 infection. We aimed to analyse paediatric mortality to inform clinical and public health policies for future influenza seasons and pandemics. All paediatric deaths related to pandemic influenza A H1N1 infection from June 26, 2009, to March 22, 2010 in England were identified through daily reporting systems and cross-checking of records and were validated by confirmation of influenza infection by laboratory results or death certificates. Clinicians responsible for each individual child provided detailed information about past medical history, presentation, and clinical course of the acute illness. Case estimates of influenza A H1N1 were obtained from the Health Protection Agency. The primary outcome measures were population mortality rates and case-fatality rates. 70 paediatric deaths related to pandemic influenza A H1N1 were reported. Childhood mortality rate was 6 per million population. The rate was highest for children aged less than 1 year. Mortality rates were higher for Bangladeshi children (47 deaths per million population [95% CI 17-103]) and Pakistani children (36 deaths per million population [18-64]) than for white British children (4 deaths per million [3-6]). 15 (21%) children who died were previously healthy; 45 (64%) had severe pre-existing disorders. The highest age-standardised mortality rate for a pre-existing disorder was for chronic neurological disease (1536 per million population). 19 (27%) deaths occurred before inpatient admission. Children in this subgroup were significantly more likely to have been healthy or had only mild pre-existing disorders than those who died after admission (p=0·0109). Overall, 45 (64%) children had received oseltamivir: seven within 48 h of symptom onset. Vaccination priority should be for children at increased risk of severe illness or death from influenza. This group might include those with specified pre-existing disorders and those in some ethnic minority groups. Early pre-hospital supportive and therapeutic care is also important. Department of Health, UK. Copyright © 2010 Elsevier Ltd. All rights reserved.
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              Assessment of baseline age-specific antibody prevalence and incidence of infection to novel influenza A/H1N1 2009.

              The objectives of the H1N1 2009 serological surveillance project were twofold: to document (1) the prevalence of cross-reactive antibodies to H1N1 2009 by age group in the population of England prior to arrival of the pandemic strain virus in the UK and (2) the age-specific incidence of infection by month as the pandemic progressed by measuring increases in the proportion of individuals with antibodies to H1N1 2009 by age. Residual aliquots of samples submitted to 16 microbiology laboratories in eight regions in England in defined age groups in 2008 and stored by the Health Protection Agency serological surveillance programme were used to document age-stratified prevalence of antibodies to H1N1 2009 prior to the arrival of the pandemic in the UK. Functional antibodies to the H1N1 2009 virus were measured by haemagglutination inhibition (HI) and microneutralisation (MN) assays. For timely measurement of monthly incidence of infection with H1N1 2009 between August 2009 and April 2010, the microbiology serum collections were supplemented by collection of residual sera from chemical pathology laboratories in England. Monthly seroincidence samples were tested by HI only, apart from the final sera collected post pandemic in 2010, which were also tested by MN. Incidence during the pandemic was estimated from changes in prevalence between time points and also by a likelihood-based method. Eight regions of England. Serum samples from patients accessing health care in England from whom blood samples were taken for unrelated microbiological or chemical pathology testing. None. Baseline age-specific prevalence of functional antibodies to the H1NI 2009 virus prior to the arrival of the pandemic; changes in antibody prevalence during the period August 2009 to April 2010. Pre-existing cross-reactive antibodies to H1N1 2009 were detected in the baseline sera and increased with age, particularly in those born before 1950. The prediction of immunological protection derived from the baseline serological analysis was consistent with the lower clinical attack rates in older age groups. The high levels of susceptibility in children < 15 years, together with their mixing within school, resulted in the highest attack rates in this age group. Serological analysis by region confirms that there were geographical differences in timing of major pandemic waves. London had a big first wave among the 5- to 14-year age group, with the rest of the country reducing the gap after the second wave. Cumulative incidence in London remained higher throughout the pandemic in each age group. By the end of the second wave it is estimated that as many as 70% of school-aged children in London had been infected. Taken together, these observations are consistent with observations from previous pandemics in 1918, 1957 and 1968 - that the major impact of influenza pandemics is on younger age groups, with a pattern of morbidity and mortality distinct from seasonal influenza epidemics. Serological analysis of appropriately structured, age-stratified and geographically representative samples can provide an immense amount of information to set in context other measures of pandemic impact in a population, and provide the most accurate measures of population exposure. National scale seroepidemiology studies require cross-agency coordination, multidisciplinary working, and considerable scientific resource. The National Institute for Health Research Health Technology Assessment programme and the Health Protection Agency.
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                Author and article information

                Journal
                Clin Infect Dis
                cid
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press
                1058-4838
                1537-6591
                01 March 2012
                19 January 2012
                19 January 2012
                : 54
                : 5
                : 661-669
                Affiliations
                [1 ]Southampton NIHR Wellcome Trust Clinical Research Facility
                [2 ]Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton
                [3 ]Southampton NIHR Respiratory Biomedical Research Unit
                [4 ]Oxford Vaccine Group, Department of Paediatrics, University of Oxford
                [5 ]Health Protection Services, Health Protection Agency, London
                [6 ]St Georges Vaccine Institute, St Georges University of London
                [7 ]Royal Devon and Exeter NHS Foundation Trust, Exeter
                [8 ]University Hospitals Bristol NHS Foundation Trust
                [9 ]Bristol Children’s Vaccine Centre, School of Clinical Sciences, University of Bristol, United Kingdom
                Author notes
                Correspondence: Saul N. Faust, MBBS MRCPCH, Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Mailpoint 218, Level C, West Wing, Tremona Rd, Southampton, United Kingdom SO16 6YD ( s.faust@ 123456soton.ac.uk ).
                Article
                10.1093/cid/cir905
                3275760
                22267719
                ba2d69f2-f5c5-4107-9b24-d752f3cb2fae
                © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please email:journals.permissions@oup.com.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 September 2011
                : 4 November 2011
                Page count
                Pages: 9
                Categories
                Articles and Commentaries

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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