Linking the seroresponse to infection to within-host heterogeneity in antibody production

Abstract

A recently published model for the serum antibody response to infection appeared well suited for use in statistical analyses of longitudinal serological data. The published model assumed exponential decay with fixed rates for pathogen and serum antibody kinetics, ignoring any within-host heterogeneity in the seroresponse. A bi-exponential model shows that there is rapid initial decay followed by a prolonged period of persistent low serum antibody concentrations. We propose a small modification of the decay model that greatly increases its flexibility by allowing for non-exponential antibody decay. The modified model produces power functions that may be interpreted as a mixture of exponential decay curves, with a mixing distribution representing the relative contribution of many centres of antibody production to the serum antibody concentration. Fitting the power function decay model to observed longitudinal data for pertussis shows improved goodness of fit compared to the exponential decay model, with estimates for the shape parameter (r=2.2; 95% CI (1.7-2.8)) that differ from exponential shape (r=1). The power function decay model predicts more persistent antibody concentrations in the long term (symptomatic threshold reached >30 years after infection) which, when used in biomarker studies, will lead to lower estimates of seroconversion rates compared to exponential antibody decay.

Assessing the stability of polio eradication after the withdrawal of oral polio vaccine

“…Absent reinfection or 239 vaccination, immunity declines over many years, possibly with increasing variation in adults. We 240 modeled waning as a power-law decay [83] during the months since last immunization, N Ab (t) ∝ t −λ , 241…”

Novel Intervention in the Aging Population: A Primary Meningococcal Vaccine Inducing Protective IgM Responses in Middle-Aged Adults

“…To study the duration of protection, we used a Bayesian approach with a multilevel longitudinal model to statistically predict the dynamics of antibody concentrations (33). We performed Markov-chain Monte Carlo simulations to find the appropriate joint distribution of parameters which best could adjust the model to the measured rSBA titer datasets for MenC, MenW, and MenY.…”

“…We performed Markov-chain Monte Carlo simulations to find the appropriate joint distribution of parameters which best could adjust the model to the measured rSBA titer datasets for MenC, MenW, and MenY. Assuming a simple exponential decay after reaching the time to peak ( t 1 ) would underestimate the persistence of protection (33–35). Therefore, we modeled the rSBA titer decay assuming that it follows a bi-exponential decay curve of the form: $y(t>t_1)=y_1\left(e^{-{\alpha }_1\left(t-t_1\right)}+f{e}^{-{\alpha }_2\left(t-t_1\right)}\right)/(1+f)$ where y 1 is the peak antibody concentration level, α 1 and α 2 are the respective decay rates of each exponential component, and f regulates the contribution of the exponential components.…”

Dynamics Affecting the Risk of Silent Circulation When Oral Polio Vaccination Is Stopped

“…Long term waning patterns, however, are poorly studied, so expert opinion may not count for much. Antibodies against other infections wane in phases with progressively slower but persistent waning (Teunis et al, 2016). Given that polio reinfections are not a threat to health, there is little reason for the immune response to polio to have evolved such that there is no ongoing waning.…”

“…An even more empirically based model of antibody level waning has recently been analyzed by (Teunis et al, 2016). The analysis, however, is for pertussis data rather than polio data.…”