Influenza B Virus Vaccine Innovation through Computational Design
Abstract
:1. Introduction
2. Evolutionary Patterns and Recent Surveillance
3. The Current State of Clinical IBV Vaccines and Trends in Immunogen Design for Pre-Clinical Vaccine Research
4. Computational Design Strategies for Influenza Vaccines
4.1. Single-Target Consensus Designs
4.2. Multivalent Computational Algorithm Designs
5. Concluding Remarks and Future Research Perspectives
Author Contributions
Funding
Conflicts of Interest
References
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Immunogen and Design | Influenza Target(s) | Vaccine Delivery Platform | Model | Study Highlights | References |
---|---|---|---|---|---|
Consensus IBV HA2 | IBV | Recombinant Adenovirus | Mouse | Intranasal prime-boost delivery induced robust IgG antibody class-switching and protected mice from lethal challenge with B/Vic. Robust ADCC induced through vaccination. Fusion peptide and transmembrane domain critical for protection from lethal challenge. | [109] |
Centralized consensus HA | H1, H2, H3, H5 IAV | Recombinant Adenovirus | Mouse | Immunization protected mice from multiple heterologous lethal challenge in a dose-dependent manner. Robust induction of IFN-γ+ splenocytes to greater levels than wild-type HA vaccines. Antibodies mediate HAI response against divergent strains within subtype. Multivalency led to increased neutralizing antibodies and IFN-γ+ splenocytes compared to commercial vaccines. Serotype switching of adenovirus vector leads to more robust HAI antibody responses in mice. | [110,111,112,113] |
Computationally optimized, broadly reactive antigens (COBRA) | H1, H2, H3, H5, N1 IAV, IBV | Virus-like particle Recombinant/conjugated protein Split-inactivated virus particle Recombinant Marek’s disease virus/turkey Herpesvirus vector Cationic lipid nanoparticle | Mouse Ferret Non-human Primate Chicken | COBRA-designed final consensus layer outperforms clade-/subtype-specific vaccine designs in homologous and heterologous antibody production while maintaining critical protein structures. HAI antibodies induced against multiple clades of viruses using homologous subtype COBRA immunization. Heterologous immunogen boosting or cocktail immunization led to increased cross-reactivity and robustness of HAI antibodies and protection from challenge compared to wild-type immunogens. Swine H1 COBRA induces HAI antibodies against both swine and human H1 strains. Nanoparticle delivery of COBRA immunization boosts T-cell response compared to VLP delivery. | [114,115,116,117,118,119,120,121,122,123,124,125,126,127] |
Mosaic algorithm HA | H1, H5 IAV | Modified Vaccinia Ankara (MVA) Plasmid DNA Recombinant Adenovirus | Mouse Non-human Primate | MVA delivery of H5 Mosaic protected mice from divergent homosubtypic challenge mediated through decreased lung inflammation and viral replication durable up to 6 months post-vaccination. T cells stimulated through H5 Mosaic vaccination possessed cross-reactivity with H1 C-terminus. Rhesus macaques vaccinated with H5 Mosaic produced antibodies against both H5 and H1 subtypes, which mediated protection through both HAI and ADCC activity post-challenge. H1 Mosaic vaccination induced broad cross-reactive antibody responses better than wild-type HA and commercial comparator vaccination. Vaccination with H1 Mosaic protected mice in dose-dependent manner. | [128,129,130] |
Epigraph algorithm HA | H3 IAV, IBV | Recombinant Adenovirus | Mouse Swine Ferret | Epigraph vaccination induced durable cross-reactive HAI antibodies and IFN-γ+ T-cell responses in BALB/c mice and pigs. Epigraph vaccination protected mice from lethal and non-lethal human H3 challenge. Protection afforded by Epigraph vaccination led to lower infectious viruses in the lungs of pigs 6-months post-vaccination. Both CD4+ and CD8+ T cells play a role in protection from lethal challenge in mice, with some evidence of non-neutralizing antibodies mediating protection. Individual immunogens differentially contributed to immune response to human H3 Epigraph vaccination. Cross-reactive immune responses were observed in ferrets along with protection from clinical and microscopic disease pathology after challenge. | [131,132,133,134] |
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Pekarek, M.J.; Weaver, E.A. Influenza B Virus Vaccine Innovation through Computational Design. Pathogens 2024, 13, 755. https://doi.org/10.3390/pathogens13090755
Pekarek MJ, Weaver EA. Influenza B Virus Vaccine Innovation through Computational Design. Pathogens. 2024; 13(9):755. https://doi.org/10.3390/pathogens13090755
Chicago/Turabian StylePekarek, Matthew J., and Eric A. Weaver. 2024. "Influenza B Virus Vaccine Innovation through Computational Design" Pathogens 13, no. 9: 755. https://doi.org/10.3390/pathogens13090755