Implementing sequence-based antigenic distance calculation into immunological shape space model

Christopher S Anderson,Sidhartha Chaudhury,Hongmei Yang,David J Topham,Mark Y Sangster,Thomas J Mariani

doi:10.1186/s12859-020-03594-3

Abstract

BackgroundIn 2009, a novel influenza vaccine was distributed worldwide to combat the H1N1 influenza “swine flu” pandemic. However, antibodies induced by the vaccine display differences in their specificity and cross-reactivity dependent on pre-existing immunity. Here, we present a computational model that can capture the effect of pre-existing immunity on influenza vaccine responses. The model predicts the region of the virus hemagglutinin (HA) protein targeted by antibodies after vaccination as well as the level of cross-reactivity induced by the vaccine. We tested our model by simulating a scenario similar to the 2009 pandemic vaccine and compared the results to antibody binding data obtained from human subjects vaccinated with the monovalent 2009 H1N1 influenza vaccine.ResultsWe found that both specificity and cross-reactivity of the antibodies induced by the 2009 H1N1 influenza HA protein were affected by the viral strain the individual was originally exposed. Specifically, the level of antigenic relatedness between the original exposure HA antigen and the 2009 HA protein affected antigenic-site immunodominance. Moreover, antibody cross-reactivity was increased when the individual’s pre-existing immunity was specific to an HA protein antigenically distinct from the 2009 pandemic strain. Comparison of simulation data with antibody binding data from human serum samples demonstrated qualitative and quantitative similarities between the model and real-life immune responses to the 2009 vaccine.ConclusionWe provide a novel method to evaluate expected outcomes in antibody specificity and cross-reactivity after influenza vaccination in individuals with different influenza HA antigen exposure histories. The model produced similar outcomes as what has been previously reported in humans after receiving the 2009 influenza pandemic vaccine. Our results suggest that differences in cross-reactivity after influenza vaccination should be expected in individuals with different exposure histories.

Highlights

In 2009, a novel influenza vaccine was distributed worldwide to combat the H1N1 influenza “swine flu” pandemic
Three strains were used as immunogens in the model (Fig. 1) including the 1918-pandemic strain, A/South Carolina/1/1918 (SC18); the 2007 vaccine strain, A/Brisbane/59/2007 (BR07); and the 2009-pandemic vaccine strain, A/ California/07/2009 (CA09)
Strings were created in such a way that the Hamming distance between them was equivalent to the antigenic distance estimated for each of the 5 antigenic-sites on the head region of HA

Summary

Introduction

In 2009, a novel influenza vaccine was distributed worldwide to combat the H1N1 influenza “swine flu” pandemic. Antibodies induced by the vaccine display differences in their specificity and cross-reactivity dependent on pre-existing immunity. Upon first exposure to influenza virus (or influenza-derived viral antigens), randomly-assembled immunoglobulin receptors on naïve B cells will bind specific parts of the virus and form germinal centers, resulting in differentiation of long-lived memory B cells and antibody-secreting cells specific to that part of the virus [1]. Memory B cells with immunoglobulin receptors specific to these more conserved parts of the virus will still be able to bind (i.e. be cross-reactive to the antigenically drifted virus) and will quickly form germinal centers resulting in additional memory B cells and antibodysecreting cells specific to the conserved part on the virus [7, 9, 10]

Objectives

Methods

Results

Discussion

Conclusion