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CodagenixCodagenix is a clinical-stage synthetic biology company specializing in the design and development of live-attenuated vaccines and viral therapeutics for infectious diseases, cancer, and animal health. Utilizing a proprietary platform that combines codon deoptimization and synthetic biology, Codagenix rapidly engineers viral genomes to create stable, broadly immunogenic, and scalable solutions. Its pipeline includes vaccines targeting dengue, RSV, influenza, COVID-19, yellow fever, Zika, and foot-and-mouth disease, as well as virotherapeutics for cancer and animal health. The company partners with academic institutions, global health organizations, and federal agencies to address critical global health challenges.
Codagenix is a clinical-stage synthetic biology company specializing in the design and development of live-attenuated vaccines and viral therapeutics for infectious diseases, cancer, and animal health. Utilizing a proprietary platform that combines codon deoptimization and synthetic biology, Codagenix rapidly engineers viral genomes to create stable, broadly immunogenic, and scalable solutions. Its pipeline includes vaccines targeting dengue, RSV, influenza, COVID-19, yellow fever, Zika, and foot-and-mouth disease, as well as virotherapeutics for cancer and animal health. The company partners with academic institutions, global health organizations, and federal agencies to address critical global health challenges.
Publication Number
US-12168049-B2
Publication Date
2024-12-17
Expiration Date
Abstract
The present invention provides for modified Flavivirus such as a modified Zika virus. The modification according to various aspects of the invention results in reduced viral proteins compared to a parent virus, wherein the reduction in expression is the result of recoding one or more regions of the virus. For example, the prM, or envelope (E) region, or the nonstructural protein 3 (NS3) region or both the E and NS3 regions can be recoded. In various embodiments one or more regions are recoded by reducing the codon pair bias or codon usage bias of the protein-encoding sequence. These modified Flavivirus are used as vaccine compositions to provide a protective immune response.
Core Innovation
The invention relates to a modified Zika virus vaccine strategy in which expression of viral proteins is reduced compared to a parent virus. The reduction is achieved by recoding at least the envelope (E) region so that the envelope (E) region is encoded by a nucleic acid having SEQ ID NO:8 or SEQ ID NO:9, and the recoding reduces codon pair bias while less than the entire E region is deoptimized.
The modified virus is configured to maintain a safety factor defined as LD50/PD50, and the description reports a safety factor of at least 10 or at least 10^2. The disclosed subject matter also includes attenuated Zika virus and other flavivirus vaccine candidates, including SAVE-deoptimized variants and nucleic acid constructs associated with SEQ ID NO:1-9.
The document further describes immunogenicity and protection arising from the modified virus, including prime-boost regimens and cross-protective or cross-reactive immune responses against heterologous flaviviruses. It characterizes attenuation and safety in model systems and reports immune outcomes such as neutralizing, FRNT, and PRNT measures, including indications of sterilizing immunity.
Claims Coverage
The relevant independent claims are directed to a modified Zika virus with reduced viral protein expression through recoding of the envelope (E) region, together with a quantified safety factor defined by LD50/PD50 and envelope (E) encoding by SEQ ID NO:8 or SEQ ID NO:9. Additional claims cover prophylactic administration, optional adjuvant use, and cross-reactive immune response language.
Modified Zika virus with reduced expression by envelope (E) recoding
A modified Zika virus in which expression of viral proteins is reduced compared to a parent virus, wherein the reduction in expression is the result of recoding at least the envelope (E) region.
Reducing codon pair bias while deoptimizing less than entire envelope (E) region
recoding at least the envelope (E) region comprises reducing the codon pair bias; wherein less than the entire of the E region is deoptimized.
Safety factor based on LD50/PD50 of at least 10 or 10^2
The modified virus has a safety factor of at least 10 or at least 10^2, wherein the safety factor is defined by the ratio of LD50/PD50.
Envelope (E) region encoded by SEQ ID NO:8 or SEQ ID NO:9
The envelope (E) region is encoded by a nucleic acid having SEQ ID NO:8 or SEQ ID NO:9.
Prophylactic immune response elicitation using the modified virus
A method for eliciting an immune response by prophylactically administering an immunogenic composition including a modified virus having reduced viral protein expression resulting from recoding at least the envelope (E) region.
Optional adjuvant administration
The method includes administering at least one adjuvant to the subject.
Cross-reactive immune response to a heterologous Zika virus
The method elicits an immune response that is cross-reactive with a heterologous Zika virus.
Overall claim coverage is centered on a modified Zika virus defined by envelope (E) recoding that reduces codon pair bias without deoptimizing the entire E region, a safety factor defined by LD50/PD50 of at least 10 or 10^2, and envelope (E) encoding by SEQ ID NO:8 or SEQ ID NO:9. Dependent claims further cover prophylactic immune-response elicitation using this modified virus, optionally with an adjuvant, and specify cross-reactive immune response language.
Stated Advantages
Improved safety characterized by a safety factor defined by LD50/PD50 of at least 10 or at least 10^2.
Cross-protective or cross-reactive immune responses against heterologous Zika or other heterologous flaviviruses are described.
Prime-boost vaccination regimens are described with immunogenicity and protection outcomes.
Attenuated vaccine candidates are described as producing protective immune response.
Documented Applications
Prophylactic administration of an immunogenic composition comprising the modified virus to elicit an immune response in a subject.
Prophylactic immune response elicitation with optional co-administration of at least one adjuvant.
Eliciting an immune response that is cross-reactive with a heterologous Zika virus.
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