Publications
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Minter A, Hoschler K, Jagne YJ, et al., 2020, Estimation of Seasonal Influenza Attack Rates and Antibody Dynamics in Children Using Cross-Sectional Serological Data, JOURNAL OF INFECTIOUS DISEASES, Vol: 225, Pages: 1750-1754, ISSN: 0022-1899
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Hay JA, Laurie K, White M, et al., 2019, Characterising antibody kinetics from multiple influenza infection and vaccination events in ferrets, PLOS COMPUTATIONAL BIOLOGY, Vol: 15
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Hay JA, Nouvellet P, Donnelly CA, et al., 2018, Potential inconsistencies in Zika surveillance data and our understanding of risk during pregnancy, PLoS Neglected Tropical Diseases, Vol: 12, ISSN: 1935-2727
BackgroundA significant increase in microcephaly incidence was reported in Northeast Brazil at the end of 2015, which has since been attributed to an epidemic of Zika virus (ZIKV) infections earlier that year. Further incidence of congenital Zika syndrome (CZS) was expected following waves of ZIKV infection throughout Latin America; however, only modest increases in microcephaly and CZS incidence have since been observed. The quantitative relationship between ZIKV infection, gestational age and congenital outcome remains poorly understood.Methodology/Principle findingsWe characterised the gestational-age-varying risk of microcephaly given ZIKV infection using publicly available incidence data from multiple locations in Brazil and Colombia. We found that the relative timings and shapes of ZIKV infection and microcephaly incidence curves suggested different gestational risk profiles for different locations, varying in both the duration and magnitude of gestational risk. Data from Northeast Brazil suggested a narrow window of risk during the first trimester, whereas data from Colombia suggested persistent risk throughout pregnancy. We then used the model to estimate which combination of behavioural and reporting changes would have been sufficient to explain the absence of a second microcephaly incidence wave in Bahia, Brazil; a population for which we had two years of data. We found that a 18.9-fold increase in ZIKV infection reporting rate was consistent with observed patterns.ConclusionsOur study illustrates how surveillance data may be used in principle to answer key questions in the absence of directed epidemiological studies. However, in this case, we suggest that currently available surveillance data are insufficient to accurately estimate the gestational-age-varying risk of microcephaly from ZIKV infection. The methods used here may be of use in future outbreaks and may help to inform improved surveillance and interpretation in countries yet to experience an out
Hay JA, Laurie K, White M, et al., 2018, Characterising antibody kinetics from multiple influenza infection and vaccination events in ferrets
<jats:title>Abstract</jats:title><jats:p>The strength and breadth of an individual’s antibody repertoire are important predictors of their response to influenza infection or vaccination. Although progress has been made in understanding qualitatively how repeated exposures shape the antibody mediated immune response, quantitative understanding remains limited. We developed a set of mathematical models describing short-term antibody kinetics following influenza infection or vaccination and fit them to haemagglutination inhibition (HI) titres from 5 groups of ferrets which were exposed to different combinations of trivalent inactivated influenza vaccine (TIV with or without adjuvant), A/H3N2 priming inoculation and post-vaccination A/H1N1 inoculation. We fit models with various immunological mechanisms that have been empirically observed but are yet to be included in mathematical models of antibody landscapes, including titre ceiling effects, antigenic seniority and exposure-type specific cross reactivity. Based on the parameter estimates of the best supported models, we describe a number of key immunological features. We found quantifiable differences in the degree of homologous and cross-reactive antibody boosting elicited by different exposure types. Infection and adjuvanted vaccination generally resulted in strong, broadly reactive responses whereas unadjuvanted vaccination resulted in a weak, narrow response. We found that the order of exposure mattered: priming with A/H3N2 improved subsequent vaccine response, and the second dose of adjuvanted vaccination resulted in substantially greater antibody boosting than the first. Either antigenic seniority or a titre ceiling effect were included in the two best fitting models, suggesting that a mechanism describing diminishing antibody boosting with repeated exposures improved the predictive power of the model. Although there was considerable uncertainty in our estimates of antibody waning paramet
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