Live attenuated influenza virus vaccines by computer-aided rational design
Open accessAbstract
Despite existing vaccines and enormous efforts in biomedical research, influenza annually claims 250,000-500,000 lives worldwide, motivating the search for new, more effective vaccines that can be rapidly designed and easily produced. We applied the previously described synthetic attenuated virus engineering (SAVE) approach to influenza virus strain A/PR/8/34 to rationally design live attenuated influenza virus vaccine candidates through genome-scale changes in codon-pair bias. As attenuation is based on many hundreds of nucleotide changes across the viral genome, reversion of the attenuated variant to a virulent form is unlikely. Immunization of mice by a single intranasal exposure to codon pair-deoptimized virus conferred protection against subsequent challenge with wild-type (WT) influenza virus. The method can be applied rapidly to any emerging influenza virus in its entirety, an advantage that is especially relevant when dealing with seasonal epidemics and pandemic threats, such as H5N1- or 2009-H1N1 influenza.
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Codon pair preference has been found in every species studied and can be radically dissimilar between phylogenetically distant species.
“Codon pair preference has been found in every species studied and can be radically dissimilar between phylogenetically distant species (Moura et al., 2005;Mueller et al., 2010).”
From Codon Pair Bias Is a Direct Consequence of Dinucleotide Bias (2016) · cites this paper as Mueller et al., 2010
Mammals share essentially the same codon pair bias, which can be different among phylogenetically distant species.
“Mammals share essentially the same codon pair bias, which can be different among phylogenetically distant species (Mueller et al., 2010).”
From Codon Pair Bias Is a Direct Consequence of Dinucleotide Bias (2016) · cites this paper as Mueller et al., 2010
Codon pair deoptimization (CPD) is a highly efficient virus attenuation strategy that utilizes suboptimal codon pairs to achieve attenuation of recoded viruses.
“Codon pair deoptimization (CPD) is a highly efficient virus attenuation strategy that utilizes suboptimal codon pairs to achieve attenuation of recoded viruses.”
From Mechanism of Virus Attenuation by Codon Pair Deoptimization (2020) · cites this paper as Mueller et al., 2010
CPD rearranges the positions of existing synonymous codons in a viral gene, without changing the codon bias or amino acid composition of the encoded protein.
“CPD rearranges the positions of existing synonymous codons in a viral gene, without changing the codon bias or amino acid composition of the encoded protein (Coleman et al., 2008;Mueller et al., 2010).”
From Mechanism of Virus Attenuation by Codon Pair Deoptimization (2020) · cites this paper as Mueller et al., 2010
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References 25 · Cited by 275
Research works printed but not linked: 21
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- Authors
- Mueller, S., Coleman, J. R., Papamichail, D., Ward, C. B., Nimnual, A., Futcher, B., Skiena, S., & Wimmer, E.
- Affiliations
- Stony Brook University (US)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Mueller, Steffen
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2010-06-13
- Volume
- 28
- Issue
- 7
- Pages
- 723-726
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC2902615
- OpenAlex
- W1983438661
- Cited by
- 275
- References
- 25
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 7 · 2023: 11 · 2022: 15 · 2021: 20 · 2020: 21 · 2019: 15 · 2018: 22 · 2017: 15 · 2016: 21 · 2015: 24 · 2014: 22 · 2013: 20 · 2012: 21
- FWCI
- 13.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI-15122, R37AI015122, R01AI075219, R01AI015122, AI075219)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Keywords
- codon pair bias, rational vaccine design, A/PR/8/34, intranasal immunization, reversion to virulence, H5N1 avian influenza, 2009 H1N1 influenza, pandemic influenza preparedness
- MeSH terms
- Animals, Cells, Cultured, Codon, Dogs, Lethal Dose 50, Molecular Sequence Data, Orthomyxoviridae, Viral Vaccines, Genome, Viral, Computer-Aided Design, Mice
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