Modelling variability of the immunity build-up and waning following RNA-based vaccination

TL;DR

This paper presents a mathematical model of RNA-based COVID-19 vaccination that explains the variability in immunity duration and suggests optimal timing for booster doses based on immune response dynamics.

Contribution

The study introduces a detailed immune response model for RNA vaccines, linking immune kinetics to protection duration and vaccination scheduling.

Findings

Protection duration peaks around 100 days for most individuals.

Protection times decrease with virus variants with mutated antibody sites.

Optimal second dose timing is about 5 weeks after the first.

Abstract

RNA-based vaccination has been broadly applied in the COVID pandemic. A characteristic of the immunization was fast waning immunity. However, the time scale of this process varied considerable for virus subtypes and among individuals. Understanding the origin of this variability is crucial in order to improve future vaccination strategies. Here, we introduce a mathematical model of RNA-based vaccination and the kinetics of the induced immune response. In the model, antigens produced following vaccination rise an immune response leading to germinal center reactions and accordingly B-cell differentiation into memory B-cells and plasma cells. In a negative feedback loop, the antibodies synthesized by newly specified plasma cells shut down the germinal center reaction as well as antigen-induced differentiation of memory B-cell into plasma cells. This limits the build-up of long-lasting immunity and thus is accompanied by fast waning immunity. The detailed data available on infection with and vaccination against SARS-CoV-2 enabled computational simulation of essential processes of the immune response. By simulation, we analyzed to which extent a single or double dose vaccination provides protection against infection. We find that variability of the immune response in individuals, originating e.g. in different immune cell densities, results in a broad log-normal-like distribution of the vaccine-induced protection times that peaks around 100 days. Protection times decrease for virus variants with mutated antibody binding sites or increased replication rates. Independent of these virus specifics, our simulations suggest optimal timing of a second dose about 5 weeks after the first in agreement with clinical trials.