Long term intrinsic cycling in human life course antibody responses to influenza A(H3N2): an observational and modeling study
- Department of Biology, University of Florida, United States
- Emerging Pathogens Institute, University of Florida, United States
- WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, United States
- Department of Epidemiology, UNC Gillings School of Global Public Health, United States
- UNC Carolina Population Center, United States
- Centre for Health Informatics Computing and Statistics, Lancaster University, United Kingdom
- Guangdong‐Hong Kong Joint Laboratory of Emerging Infectious Diseases/MOE Joint Laboratory for International Collaboration in Virology and Emerging Infectious Diseases, Joint Institute of Virology (Shantou University/The University of Hong Kong), Shantou University, China
- State Key Laboratory of Emerging Infectious Diseases / World Health Organization Influenza Reference Laboratory, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China
- EKIH (Gewuzhikang) Pathogen Research Institute, China
- Department of Ecology and Evolutionary Biology, Princeton University, United States
- MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, United Kingdom
- Center for Communicable Disease Dynamics, Harvard TH Chan School of Public Health, United States
- The Jockey Club School of Public Health and Primary Care, Chinese University of Hong Kong, China
- Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, China
- Shenzhen Research Institute of The Chinese University of Hong Kong, China
- Guangzhou No.12 Hospital, Guangzhou, China
Figures
Figure 1 with 8 supplements
Long-term cycles in individual antibody responses to influenza A(H3N2) at baseline.
(A) Hemagglutination inhibition (HI) titers against A(H3N2) strains at baseline. Each row shows an antibody profile for a participant. Participants are sorted by age (y-axis). Strains (x-axis) are …
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Figure 1—source data 1
Variance (%) explained by low frequencies and peak frequencies for Fourier spectra of individual residuals.
- https://cdn.elifesciences.org/articles/81457/elife-81457-fig1-data1-v2.docx
Figure 1—figure supplement 1
Long-term cycles in individual antibody responses to influenza A(H3N2) at follow-up.
(A) Hemagglutination inhibition (HI) titers against A(H3N2) strains at follow-up. Each row shows an antibody profile for a participant. Participants are sorted by age (y-axis). Strains (x-axis) are …
Figure 1—figure supplement 2
Representative individual profiles of hemagglutination inhibition (HI) titers.
(A-I) Random selected individuals from 777 participants with their ages shown shown in each panel. Light gray circles and dark gray triangles are antibody measures for baseline and follow-up visit, …
Figure 1—figure supplement 3
Antigenic map and paired antigenic distances of influenza A(H3N2) strains.
(A) Antigenic maps and locations of strains that were tested in our study. The antigenic map was generated using estimates by Fonville et al., 2014. We labeled our tested strains that were also …
Figure 1—figure supplement 4
Conceptual plot for individual life-course immune responses to influenza.
(A) Simulated annual antibody profiles of a representative individual born in 1977 and who had four infections (1977, 1994, 2003, and 2006) (same as in D). Each row represents the antibody profile …
Figure 1—figure supplement 5
Representative individual profiles of residuals of hemagglutination inhibition (HI) titers.
(A-I) Random selected individuals from 777 participants with their ages shown shown in each panel. Profiles are from the same individuals shown in Figure 1—figure supplement 2. Residuals were …
Figure 1—figure supplement 6
Illustration of estimation of individual time series of residuals and Fourier analysis of observed and permutation of time series.
(A) Observed hemagglutination inhibition (HI) titers, estimated HI titers, and residuals. Estimations were derived from the generalized additive model (GAM) of log HI titers on age at sampling …
Figure 1—figure supplement 7
Validation using values generated from random distributions with no periodicity.
777 time series were simulated, and the lengths and resolutions of the time series were the same as the data. Colored lines are distributions of peak frequencies for yearly interpolation of the …
Figure 1—figure supplement 8
Validation using values generated from periodic curves.
A sine curve with predefined periodicity and white noise was simulated on a yearly basis, and values for the time points when tested A(H3N2) strains were isolated were extracted. 777 time series …
Figure 2 with 5 supplements
Impacts of irregularly sampled data, interpolations, and long-term trends on cycles identified in individual antibody responses at baseline.
(A) Distribution of weighted frequencies of individual Fourier spectra at baseline. We performed Fourier spectral analysis on the interpolated time series of residuals for each person and calculated …
Figure 2—figure supplement 1
Comparison of time series of residuals and their Fourier spectra before and after empirical mode decomposition (EMD).
Left columns represent time series of residuals before (green) and after (blue) detrending using EMD. The orange line indicates the nonlinear trend identified using EMD. Right columns represent the …
Figure 2—figure supplement 2
Distribution of peak frequencies across individuals when dropping titers of one tested strain for serums collected at baseline.
Light green lines indicate the distribution of peak frequencies in the data. Median (thick gray ticks), interquartile (gray bars), and 95% intervals (think gray ticks) of Fourier spectra from 1000 …
Figure 2—figure supplement 3
Distribution of peak frequencies across individuals when dropping titers of one tested strain for serums collected at follow-up.
Dark green lines indicate the distribution of peak frequencies in the data. Median (thick gray ticks), interquartile (gray bars), and 95% intervals (think gray ticks) of Fourier spectra from 1000 …
Figure 2—figure supplement 4
Distribution of peak frequencies across individuals born before 1968.
(A) Serums collected at baseline. (B) Serums collected during the follow-up visit. We performed Fourier spectral analysis on the time series of residuals and extracted peak frequencies for a subset …
Figure 2—figure supplement 5
Cycles in immune responses to influenza in the Vietnam data.
(A–F) show distributions of frequencies that explain the most variance across 69 individuals, whose serums were annually collected from 2007 to 2012. The Vietnam data was taken from Bedford et al., …
Figure 3 with 2 supplements
Cycles in simulated antibody responses from the model accounted for different mechanisms.
Colored lines are the distribution of peak frequencies detected in the simulated antibody profiles across individuals. Gray lines are the distributions of peak frequencies of the 1000 permutations …
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Figure 3—source data 1
Parameters used in the simulations.
- https://cdn.elifesciences.org/articles/81457/elife-81457-fig3-data1-v2.docx
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Figure 3—source data 2
Mechanisms examined in the simulations.
- https://cdn.elifesciences.org/articles/81457/elife-81457-fig3-data2-v2.docx
Figure 3—figure supplement 1
Conceptual plot of modeling immune responses.
The black line in the top-left panel denotes pre-season (e.g., 2003) antibody profile, from which the titer of the circulating strain (filled point) was used to determine the probability of …
Figure 3—figure supplement 2
Impact of antigenic evolution speed on the reported cycles in individual antibody responses.
Green and purple lines indicate the distribution of peak frequencies detected in the observed simulated antibody profiles across individuals. Gray lines are the distributions of peak frequencies of …
Figure 4 with 1 supplement
Predicting seroconversion to the recently circulated strains using phases of individual antibody responses.
(A) Concept plot for phases. Four phases were classified based on the phase angles between 0 and 360°. (B) Illustration of predicting phase in 2012 using individual residuals from baseline …
Figure 4—figure supplement 1
Impact of periodicity on predictions of cohort-specific phases and seroconversions to circulating strains.
Predictions of phases in 2012 were derived using hemagglutination inhibition (HI) titers against strains isolated between 1968 and 2002, assuming individual antibody responses with periodicity of 35 …
