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Implementing sequence-based antigenic distance calculation into immunological shape space model
- Source :
- BMC Bioinformatics, BMC Bioinformatics, Vol 21, Iss 1, Pp 1-13 (2020)
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
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.
- Subjects :
- 0301 basic medicine
HA
Hemagglutinin Glycoproteins, Influenza Virus
Antibodies, Viral
Biochemistry
Epitopes
Influenza A Virus, H1N1 Subtype
0302 clinical medicine
Structural Biology
Pandemic
Hemagglutinin
lcsh:QH301-705.5
Antigens, Viral
Vaccines
Shape space
Stalk
biology
Applied Mathematics
H1N1
Gillespie algorithm
2009 pandemic
Computer Science Applications
Vaccination
Influenza Vaccines
lcsh:R858-859.7
Antigenic distance
Research Article
Simulations
Influenza vaccine
Humoral immune system
Hemagglutinin (influenza)
Immunodominance
Cross Reactions
Stem
lcsh:Computer applications to medicine. Medical informatics
Virus
03 medical and health sciences
Antigen
Immunity
Humans
Computer Simulation
Amino Acid Sequence
Computational immunology
Molecular Biology
Artificial immune systems
Models, Immunological
pH1N1
Virology
Influenza
Antigenic sites
030104 developmental biology
lcsh:Biology (General)
biology.protein
030215 immunology
Subjects
Details
- ISSN :
- 14712105
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- BMC Bioinformatics
- Accession number :
- edsair.doi.dedup.....bf6fddd28eafd58dcfe5357ad597e355