Implementing Sequence-based Antigenic Distance Calculation into Immunological Shape Space Model

Overview

Journal BMC Bioinformatics

Publisher Biomed Central

Specialty Biology

Date 2020 Jun 21

PMID 32560624

Citations 1

Authors

Christopher S Anderson

Mark Y Sangster

Hongmei Yang

Thomas J Mariani

Sidhartha Chaudhury

David J Topham

Affiliations

Soon will be listed here.

Abstract

Background: In 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.

Results: We 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.

Conclusion: We 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.

Citing Articles

First Impressions Matter: Immune Imprinting and Antibody Cross-Reactivity in Influenza and SARS-CoV-2.

King S, Bryan S, Hilchey S, Wang J, Zand M Pathogens. 2023; 12(2).

PMID: 36839441 PMC: 9967769. DOI: 10.3390/pathogens12020169.

References

Tesini B, Kanagaiah P, Wang J, Hahn M, Halliley J, Chaves F . Broad Hemagglutinin-Specific Memory B Cell Expansion by Seasonal Influenza Virus Infection Reflects Early-Life Imprinting and Adaptation to the Infecting Virus. J Virol. 2019; 93(8). PMC: 6450111. DOI: 10.1128/JVI.00169-19. View

DeDiego M, Anderson C, Yang H, Holden-Wiltse J, Fitzgerald T, Treanor J . Directed selection of influenza virus produces antigenic variants that match circulating human virus isolates and escape from vaccine-mediated immune protection. Immunology. 2016; 148(2):160-73. PMC: 4863573. DOI: 10.1111/imm.12594. View

Mosterin Hopping A, McElhaney J, Fonville J, Powers D, Beyer W, Smith D . The confounded effects of age and exposure history in response to influenza vaccination. Vaccine. 2015; 34(4):540-546. PMC: 4724805. DOI: 10.1016/j.vaccine.2015.11.058. View

Ndifon W, Wingreen N, Levin S . Differential neutralization efficiency of hemagglutinin epitopes, antibody interference, and the design of influenza vaccines. Proc Natl Acad Sci U S A. 2009; 106(21):8701-6. PMC: 2688967. DOI: 10.1073/pnas.0903427106. View

ODonnell C, Wright A, Vogel L, Wei C, Nabel G, Subbarao K . Effect of priming with H1N1 influenza viruses of variable antigenic distances on challenge with 2009 pandemic H1N1 virus. J Virol. 2012; 86(16):8625-33. PMC: 3421718. DOI: 10.1128/JVI.00147-12. View

Li G, Chiu C, Wrammert J, McCausland M, Andrews S, Zheng N . Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells. Proc Natl Acad Sci U S A. 2012; 109(23):9047-52. PMC: 3384143. DOI: 10.1073/pnas.1118979109. View

Pan K, Subieta K, Deem M . A novel sequence-based antigenic distance measure for H1N1, with application to vaccine effectiveness and the selection of vaccine strains. Protein Eng Des Sel. 2010; 24(3):291-9. PMC: 3038458. DOI: 10.1093/protein/gzq105. View

Chambers B, Parkhouse K, Ross T, Alby K, Hensley S . Identification of Hemagglutinin Residues Responsible for H3N2 Antigenic Drift during the 2014-2015 Influenza Season. Cell Rep. 2015; 12(1):1-6. PMC: 4487778. DOI: 10.1016/j.celrep.2015.06.005. View

Anderson C, Ortega S, Chaves F, Clark A, Yang H, Topham D . Natural and directed antigenic drift of the H1 influenza virus hemagglutinin stalk domain. Sci Rep. 2017; 7(1):14614. PMC: 5668287. DOI: 10.1038/s41598-017-14931-7. View

10.

Du X, Dong L, Lan Y, Peng Y, Wu A, Zhang Y . Mapping of H3N2 influenza antigenic evolution in China reveals a strategy for vaccine strain recommendation. Nat Commun. 2012; 3:709. DOI: 10.1038/ncomms1710. View

11.

Li Y, Myers J, Bostick D, Sullivan C, Madara J, Linderman S . Immune history shapes specificity of pandemic H1N1 influenza antibody responses. J Exp Med. 2013; 210(8):1493-500. PMC: 3727314. DOI: 10.1084/jem.20130212. View

12.

Edgar R . MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 2004; 32(5):1792-7. PMC: 390337. DOI: 10.1093/nar/gkh340. View

13.

Lee H, Topham D, Park S, Hollenbaugh J, Treanor J, Mosmann T . Simulation and prediction of the adaptive immune response to influenza A virus infection. J Virol. 2009; 83(14):7151-65. PMC: 2704765. DOI: 10.1128/JVI.00098-09. View

14.

Anderson C, DeDiego M, Thakar J, Topham D . Novel Sequence-Based Mapping of Recently Emerging H5NX Influenza Viruses Reveals Pandemic Vaccine Candidates. PLoS One. 2016; 11(8):e0160510. PMC: 4975393. DOI: 10.1371/journal.pone.0160510. View

15.

Kirkpatrick E, Qiu X, Wilson P, Bahl J, Krammer F . The influenza virus hemagglutinin head evolves faster than the stalk domain. Sci Rep. 2018; 8(1):10432. PMC: 6041311. DOI: 10.1038/s41598-018-28706-1. View

16.

Ndifon W . A simple mechanistic explanation for original antigenic sin and its alleviation by adjuvants. J R Soc Interface. 2015; 12(112). PMC: 4685838. DOI: 10.1098/rsif.2015.0627. View

17.

Chaudhury S, Reifman J, Wallqvist A . Simulation of B cell affinity maturation explains enhanced antibody cross-reactivity induced by the polyvalent malaria vaccine AMA1. J Immunol. 2014; 193(5):2073-86. PMC: 4135178. DOI: 10.4049/jimmunol.1401054. View

18.

Smith D, Forrest S, Ackley D, Perelson A . Using lazy evaluation to simulate realistic-size repertoires in models of the immune system. Bull Math Biol. 1998; 60(4):647-58. DOI: 10.1006/bulm.1997.0035. View

19.

Russell C, Jones T, Barr I, Cox N, Garten R, Gregory V . Influenza vaccine strain selection and recent studies on the global migration of seasonal influenza viruses. Vaccine. 2009; 26 Suppl 4:D31-4. DOI: 10.1016/j.vaccine.2008.07.078. View

20.

Wu A, Peng Y, Du X, Shu Y, Jiang T . Correlation of influenza virus excess mortality with antigenic variation: application to rapid estimation of influenza mortality burden. PLoS Comput Biol. 2010; 6(8). PMC: 2920844. DOI: 10.1371/journal.pcbi.1000882. View