Dataset Information

Individual and Population Trajectories of Influenza Antibody Titers Over Multiple Seasons in a Tropical Country.

ABSTRACT: Seasonal influenza epidemics occur year-round in the tropics, complicating the planning of vaccination programs. We built an individual-level longitudinal model of baseline antibody levels, time of infection, and the subsequent rise and decay of antibodies postinfection using influenza A(H1N1)pdm09 data from 2 sources in Singapore: 1) a noncommunity cohort with real-time polymerase chain reaction-confirmed infections and at least 1 serological sample collected from each participant between May and October 2009 (n = 118) and 2) a community cohort with up to 6 serological samples collected between May 2009 and October 2010 (n = 760). The model was hierarchical, to account for interval censoring and interindividual variation. Model parameters were estimated via a reversible jump Markov chain Monte Carlo algorithm using custom-designed R (https://www.r-project.org/) and C++ (https://isocpp.org/) code. After infection, antibody levels peaked at 4-7 weeks, with a half-life of 26.5 weeks, followed by a slower decrease up to 1 year to approximately preinfection levels. After the third wave, the seropositivity rate and the population-level antibody titer dropped to the same level as they were at the end of the first pandemic wave. The results of this analysis are consistent with the hypothesis that the population-level effect of individuals' waxing and waning antibodies influences influenza seasonality in the tropics.

SUBMITTER: Zhao X

PROVIDER: S-EPMC5860523 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Individual and Population Trajectories of Influenza Antibody Titers Over Multiple Seasons in a Tropical Country.

Zhao Xiahong X Ning Yilin Y Chen Mark I-Cheng MI Cook Alex R AR

American journal of epidemiology 20180101 1

Seasonal influenza epidemics occur year-round in the tropics, complicating the planning of vaccination programs. We built an individual-level longitudinal model of baseline antibody levels, time of infection, and the subsequent rise and decay of antibodies postinfection using influenza A(H1N1)pdm09 data from 2 sources in Singapore: 1) a noncommunity cohort with real-time polymerase chain reaction-confirmed infections and at least 1 serological sample collected from each participant between May a ...[more]

PMID: 29309522

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Project description:Antibodies to influenza surface protein neuraminidase (NA) have been found to reduce disease severity and may be an independent correlate of protection. Despite this, current influenza vaccines have no regulatory requirements for the quality or quantity of the NA antigen and are not optimized for induction of NA-specific antibodies. Here we investigate the induction and durability of NA-specific antibody titers after pandemic AS03-adjuvanted monovalent H1N1 vaccination and subsequent annual vaccination in health care workers in a five-year longitudinal study. NA-specific antibodies were measured by endpoint ELISA and functional antibodies measured by enzyme-linked lectin assay (ELLA) and plaque reduction naturalisation assay. We found robust induction of NA inhibition (NAI) titers with a 53% seroconversion rate (>4-fold) after pandemic vaccination in 2009. Furthermore, the endpoint and NAI geometric mean titers persisted above pre-vaccination levels up to five years after vaccination in HCWs that only received the pandemic vaccine, which demonstrates considerable durability. Vaccination with non-adjuvanted trivalent influenza vaccines (TIV) in subsequent influenza seasons 2010/2011 - 2013/2014 further boosted NA-specific antibody responses. We found that each subsequent vaccination increased durable endpoint titers and contributed to maintaining the durability of functional antibody titers. Although the trivalent influenza vaccines boosted NA-specific antibodies, the magnitude of fold-increase at day 21 declined with repeated vaccination, particularly for functional antibody titers. High levels of pre-existing antibodies were associated with lower fold-induction in repeatedly vaccinated HCWs. In summary, our results show that durable NA-specific antibody responses can be induced by an adjuvanted influenza vaccine, which can be maintained and further boosted by TIVs. Although NA-specific antibody responses are boosted by annual influenza vaccines, high pre-existing titers may negatively affect the magnitude of fold-increase in repeatedly vaccinated individuals. Our results support continued development and standardization of the NA antigen to supplement current influenza vaccines and reduce the burden of morbidity and mortality.

Dataset Information

Individual and Population Trajectories of Influenza Antibody Titers Over Multiple Seasons in a Tropical Country.

Publications

Individual and Population Trajectories of Influenza Antibody Titers Over Multiple Seasons in a Tropical Country.

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