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Novel Sequence-Based Mapping of Recently Emerging H5NX Influenza Viruses Reveals Pandemic Vaccine Candidates
Christopher S Anderson1, Marta L DeDiego1, Juilee Thakar1,2
1New York Influenza Center of Excellence, David Smith Center for Immunology and Vaccine Biology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, United States of America.
Abstract:
Recently, an avian influenza virus, H5NX subclade 2.3.4.4, emerged and spread to North America. This subclade has frequently reassorted, leading to multiple novel viruses capable of human infection. Four cases of human infections, three leading to death, have already occurred. Existing vaccine strains do not protect against these new viruses, raising a need to identify new vaccine candidate strains. We have developed a novel sequence-based mapping (SBM) tool capable of visualizing complex protein sequence data sets using a single intuitive map. We applied SBM on the complete set of avian H5 viruses in order to better understand hemagglutinin protein variance amongst H5 viruses and identify any patterns associated with this variation. The analysis successfully identified the original reassortments that lead to the emergence of this new subclade of H5 viruses, as well as their known unusual ability to re-assort among neuraminidase subtypes. In addition, our analysis revealed distinct clusters of 2.3.4.4 variants that would not be covered by existing strains in the H5 vaccine stockpile. The results suggest that our method may be useful for pandemic candidate vaccine virus selection.
Insights
A new avian influenza virus (H5NX 2.3.4.4) is a threat to human health. A novel sequence-based mapping tool identified distinct viral variants, aiding in selecting new vaccine candidates for pandemic preparedness.
Area of Science:
- Virology
- Genomics
- Vaccinology
Background:
- Avian influenza virus H5NX subclade 2.3.4.4 has emerged and spread globally.
- This subclade has caused human infections and deaths, with existing vaccines being ineffective.
- There is an urgent need for new vaccine candidate strains against emerging H5NX viruses.
Purpose of the Study:
- To understand hemagglutinin protein variation in H5 viruses.
- To identify patterns associated with H5NX subclade 2.3.4.4 emergence and reassortment.
- To identify novel vaccine candidate strains for pandemic preparedness.
Main Methods:
- Development of a novel sequence-based mapping (SBM) tool for visualizing protein sequence data.
- Application of SBM to the complete set of avian H5 viruses.
- Analysis of hemagglutinin protein variance and reassortment patterns.
Main Results:
- SBM successfully identified original reassortments leading to H5NX 2.3.4.4 emergence.
- The analysis confirmed the virus's ability to reassort among neuraminidase subtypes.
- Distinct clusters of 2.3.4.4 variants, not covered by current H5 vaccines, were identified.
Conclusions:
- The sequence-based mapping method is effective for analyzing viral protein variation.
- The identified viral clusters highlight gaps in existing H5 vaccine coverage.
- The SBM tool shows potential for pandemic candidate vaccine virus selection.
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