Chimpanzee adenoviral vector-based filovirus vaccines
Inventors
Sullivan, Nancy J. • Nabel, Gary J. • Asiedu, Clement • Cheng, Cheng • Nicosia, Alfredo • Cortese, Riccardo • Ammendola, Virginia • Colloca, Stefano
Assignees
Sabin Vaccine Institute • US Department of Health and Human Services
Publication Number
US-11913013-B2
Publication Date
2024-02-27
Expiration Date
2031-04-15
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Abstract
This invention provides vaccines for inducing an immune response and protection against filovirus infection for use as a preventative vaccine in humans. In particular, the invention provides chimpanzee adenoviral vectors expressing filovirus proteins from different strains of Ebolavirus (EBOV) or Marburg virus (MARV).
Core Innovation
This invention provides vaccines for inducing an immune response and protection against filovirus infection for use as a preventative vaccine in humans. In particular, the invention provides chimpanzee adenoviral vectors expressing filovirus proteins from different strains of Ebolavirus (EBOV) or Marburg virus (MARV). These vaccines include chimpanzee adenovirus serotypes such as ChAd3, ChAd63, PanAd3, PanAd1, PanAd2, or ChAd83 expressing filovirus envelope glycoprotein (GP).
The problem being solved is that Ebola (EBOV) and Marburg (MARV) viruses are highly lethal hemorrhagic fever viruses with significant mortality rates and no effective vaccines or drugs are currently available. Traditional immunization approaches have not succeeded in generating protective immune responses in primates. Furthermore, the commonly used human adenovirus 5 (rAd5) vectors for vaccine delivery may have limited efficacy due to pre-existing immunity in humans.
The invention addresses these issues by providing adenoviral vectors derived from chimpanzees to circumvent pre-existing immunity to human adenovirus vectors. These chimpanzee adenoviral vectors are replication-defective and engineered to express filovirus antigens such as glycoproteins, and may use codon-optimized sequences for improved expression. The vaccines can also be formulated with adjuvants and used in prime-boost regimens to enhance immune responses.
Claims Coverage
The patent includes one independent claim focusing on isolated nucleic acid molecules corresponding to specific sequences and compositions containing these molecules.
Isolated nucleic acid molecules comprising specific chimpanzee adenoviral vector sequences
The invention includes isolated nucleic acid molecules comprising sequences selected from SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9.
Promoter operably linked to the isolated nucleic acid molecules
The isolated nucleic acid molecules can further comprise a promoter operably linked, particularly a CMV promoter, to enable expression of the nucleic acid sequence.
Compositions comprising the isolated nucleic acid molecules and a pharmaceutically acceptable carrier
The invention covers compositions comprising the isolated nucleic acid molecules in a pharmaceutically acceptable carrier, where the nucleic acid is contained within a viral particle.
The claims focus on isolated nucleic acid molecules encoding chimpanzee adenoviral vector sequences, their operable linkage to promoters, and formulations of these molecules within pharmaceutical compositions comprising viral particles.
Stated Advantages
Chimpanzee adenoviral vectors overcome the limitations of pre-existing immunity to human adenovirus vectors such as rAd5, potentially improving vaccine efficacy.
The vectors induce strong cellular and humoral immune responses comparable or superior to rAd5 vectors following single immunization or prime-boost regimens.
The vaccines provide protective immunity against lethal filovirus challenges in nonhuman primates after a single immunization dose.
Documented Applications
Preventative vaccines for inducing protective immunity against filovirus infections including different strains of Ebolavirus (EBOV) and Marburg virus (MARV) in humans.
Use as a vaccine in prime-boost immunization schedules employing chimpanzee adenoviral vectors alone or in combination with other viral vectors such as rLCMV or rMVA.
Potential post-exposure prophylactic administration to enhance immunity against filovirus infection.
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