Age-specific incidence of A/H1N1 2009 influenza infection in England from sequential antibody prevalence data using likelihood-based estimation.

Estimating the age-specific incidence of an emerging pathogen is essential for understanding its severity and transmission dynamics. This paper describes a statistical method that uses likelihoods to estimate incidence from sequential serological data. The method requires information on seroconversion intervals and allows integration of information on the temporal distribution of cases from clinical surveillance. Among a family of candidate incidences, a likelihood function is derived by reconstructing the change in seroprevalence from seroconversion following infection and comparing it with the observed sequence of positivity among the samples. This method is applied to derive the cumulative and weekly incidence of A/H1N1 pandemic influenza in England during the second wave using sera taken between September 2009 and February 2010 in four age groups (1-4, 5-14, 15-24, 25-44 years). The highest cumulative incidence was in 5-14 year olds (59%, 95% credible interval (CI): 52%, 68%) followed by 1-4 year olds (49%, 95% CI: 38%, 61%), rates 20 and 40 times higher respectively than estimated from clinical surveillance. The method provides a more accurate and continuous measure of incidence than achieved by comparing prevalence in samples grouped by time period

Seroprevalence of influenza A(H1N1)pdm09 virus antibody, England, 2010 and 2011.

The intense influenza activity in England during the 2010-11 winter resulted from a combination of factors. Population-based seroepidemiology confirms that the third wave of influenza A(H1N1)pdm09 virus circulation was associated with a shift in age groups affected, with the highest rate of infection in young adults

Humoral Response to the Influenza A H1N1/09 Monovalent AS03-Adjuvanted Vaccine in Immunocompromised Patients

In this observational study, safety and immunogenicity after one dose of the AS03-adjuvanted influenza H1N1/09 vaccine was overall appropriate in HIV-infected patients and solid-organ transplant recipients. A second dose of the vaccine only moderately improved the antibody respons

Estimation of Seasonal Influenza Attack Rates and Antibody Dynamics in Children Using Cross-Sectional Serological Data.

Directly measuring evidence of influenza infections is difficult, especially in low-surveillance settings such as sub-Saharan Africa. Using a Bayesian model, we estimated unobserved infection times and underlying antibody responses to influenza A/H3N2, using cross-sectional serum antibody responses to 4 strains in children aged 24-60 months. Among the 242 individuals, we estimated a variable seasonal attack rate and found that most children had ≥1 infection before 2 years of age. Our results are consistent with previously published high attack rates in children. The modeling approach highlights how cross-sectional serological data can be used to estimate epidemiological dynamics

Reproducibility of Serologic Assays for Influenza Virus A (H5N1)

Results for clade 1 viruses were more consistent among laboratories when a standard antibody was used

Haemagglutination inhibition and virus microneutralisation serology assays: use of harmonised protocols and biological standards in seasonal influenza serology testing and their impact on inter-laboratory variation and assay correlation: A FLUCOP collaborative study

Introduction: The haemagglutination inhibition assay (HAI) and the virus microneutralisation assay (MN) are long-established methods for quantifying antibodies against influenza viruses. Despite their widespread use, both assays require standardisation to improve inter-laboratory agreement in testing. The FLUCOP consortium aims to develop a toolbox of standardised serology assays for seasonal influenza. Building upon previous collaborative studies to harmonise the HAI, in this study the FLUCOP consortium carried out a head-to-head comparison of harmonised HAI and MN protocols to better understand the relationship between HAI and MN titres, and the impact of assay harmonisation and standardisation on inter-laboratory variability and agreement between these methods. Methods: In this paper, we present two large international collaborative studies testing harmonised HAI and MN protocols across 10 participating laboratories. In the first, we expanded on previously published work, carrying out HAI testing using egg and cell isolated and propagated wild-type (WT) viruses in addition to high-growth reassortants typically used influenza vaccines strains using HAI. In the second we tested two MN protocols: an overnight ELISA-based format and a 3-5 day format, using reassortant viruses and a WT H3N2 cell isolated virus. As serum panels tested in both studies included many overlapping samples, we were able to look at the correlation of HAI and MN titres across different methods and for different influenza subtypes. Results: We showed that the overnight ELISA and 3-5 day MN formats are not comparable, with titre ratios varying across the dynamic range of the assay. However, the ELISA MN and HAI are comparable, and a conversion factor could possibly be calculated. In both studies, the impact of normalising using a study standard was investigated, and we showed that for almost every strain and assay format tested, normalisation significantly reduced inter-laboratory variation, supporting the continued development of antibody standards for seasonal influenza viruses. Normalisation had no impact on the correlation between overnight ELISA and 3-5 day MN formats.publishedVersio

Seroprevalence of SARS-CoV-2 among Blood Donors and Changes after Introduction of Public Health and Social Measures, London, UK.

We describe results of testing blood donors in London, UK, for severe acute respiratory disease coronavirus 2 (SARS-CoV-2) IgG before and after lockdown measures. Anonymized samples from donors 17-69 years of age were tested using 3 assays: Euroimmun IgG, Abbott IgG, and an immunoglobulin receptor-binding domain assay developed by Public Health England. Seroprevalence increased from 3.0% prelockdown (week 13, beginning March 23, 2020) to 10.4% during lockdown (weeks 15-16) and 12.3% postlockdown (week 18) by the Abbott assay. Estimates were 2.9% prelockdown, 9.9% during lockdown, and 13.0% postlockdown by the Euroimmun assay and 3.5% prelockdown, 11.8% during lockdown, and 14.1% postlockdown by the receptor-binding domain assay. By early May 2020, nearly 1 in 7 donors had evidence of past SARS-CoV-2 infection. Combining results from the Abbott and Euroimmun assays increased seroprevalence by 1.6%, 2.3%, and 0.6% at the 3 timepoints compared with Euroimmun alone, demonstrating the value of using multiple assays

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

Background. We investigated antibody persistence in children 1 year after 2 doses of either an AS03B-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 AS03B-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 AS03B-adjuvanted vaccine. Conclusions. This study provides serological evidence that 2 doses of AS03B-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